Multidisciplinary Molecular Tumor Board Research Articles

A pilot clinical trial of genomic-based therapy assignment with co-expression extrapolation (COXEN) in advanced/metastatic urothelial carcinoma.

452 Background: We investigated the Co-eXpression ExtrapolatioN (COXEN) algorithm to select “next best therapy” for patients with advanced/metastatic urothelial cancer based on gene expression profiles. Methods: This is a single-arm, open label pilot study, that investigates the COXEN algorithm’s ability to use patients’ tumor gene expression models to predict sensitivities to 75 FDA-approved anticancer agents. The COXEN results were reviewed and discussed in a multi-disciplinary molecular tumor board. From that a treatment plan was chosen based on monotherapy clinical efficacy data in urothelial carcinoma, combination safety data (combinations of agents were allowed provided phase I data were available), side effect profile/tolerability, response or resistance to prior therapies, therapy contraindications, and feasibility of therapy. The objective of this study was to determine the feasibility of using COXEN as a clinical decision algorithm to make a real-time treatment decision within 21 days of specimen collection in patients with advanced/metastatic urothelial carcinoma. Results: A total of 8 patients enrolled and underwent tumor biopsy for COXEN analysis. Five out of 8 patients received COXEN therapy within 21 days of biopsy with various regimens including: vorinostat and etoposide; doxorubicin; sunitinib; doxorubicin and paclitaxel; erlotinib and nab-paclitaxel. There were no objective responses. The 5 patients treated with COXEN therapy had a median potential follow up of 36 months, median overall survival of 8.4 months (95% CI: 5.2 months – not estimable), and median progression free survival of 2.2 months (95% CI: 1.4 – 3.9 months). Grade 3 or 4 adverse events included: febrile neutropenia (n=2), hypophosphatemia (n=1) and hyponatremia (n=1). This trial was terminated early due to a lack of treatment responses. Conclusions: The COXEN algorithm is a unique personalized method for selecting therapy for patients with advanced urothelial carcinoma. Although the COXEN method was feasible, it did not demonstrate clinical efficacy in this small cohort of patients. Clinical trial information: NCT02788201.

NGS-guided precision oncology in metastatic breast and gynecological cancer: first experiences at the CCC Munich LMU

PurposeComprehensive genomic profiling identifying actionable molecular alterations aims to enable personalized treatment for cancer patients. The purpose of this analysis was to retrospectively assess the impact of personalized recommendations made by a multidisciplinary tumor board (MTB) on the outcome of patients with breast or gynecological cancers, who had progressed under standard treatment. Here, first experiences of our Comprehensive Cancer Center Molecular Tumor Board are reported.MethodsAll patients were part of a prospective local registry. 95 patients diagnosed with metastatic breast cancer or gynecological malignancies underwent extended molecular profiling. From May 2017 through March 2019, the MTB reviewed all clinical cases considering tumor profile and evaluated molecular alterations regarding further diagnostic and therapeutic recommendations.Results95 patients with metastatic breast or gynecological cancers were discussed in the MTB (68% breast cancer, 20% ovarian cancer, 5% cervical cancer, 3% endometrial cancer and 4% others). Genes with highest mutation rate were PIK3CA and ERBB2. Overall, 34 patients (36%) received a biomarker-based targeted therapy recommendation. Therapeutic recommendations were implemented in nine cases; four patients experienced clinical benefit with a partial response or disease stabilization lasting over 4 months.ConclusionIn the setting of a multidisciplinary molecular tumor board, a small but clinically meaningful group of breast and gynecological cancer patients benefits from comprehensive genomic profiling. Broad and successful implementation of precision medicine is complicated by patient referral at late stage disease and limited access to targeted agents and early clinical trials.Trial registration number284-10 (03.05.2018).

Clinical Utilization, Utility, and Reimbursement for Expanded Genomic Panel Testing in Adult Oncology.

The routine use of large next-generation sequencing (NGS) pan-cancer panels is required to identify the increasing number of, but often uncommon, actionable alterations to guide therapy. Inconsistent coverage and variable payment is hindering NGS adoption into clinical practice. A review of test utilization, clinical utility, coverage, and reimbursement was conducted in a cohort of patients diagnosed with high-risk cancer who received pan-cancer panel testing as part of their clinical care. The Columbia Combined Cancer Panel (CCCP), a 467-gene panel designed to detect DNA variations in solid and liquid tumors, was performed in the Laboratory of Personalized Genomic Medicine at Columbia University Irving Medical Center. Utilization was characterized at test order. Results were reviewed by a molecular pathologist, followed by a multidisciplinary molecular tumor board where clinical utility was classified by consensus. Reimbursement was reviewed after payers provided final coverage decisions. NGS was performed on 359 high-risk tumors from 349 patients. Reimbursement data were available for 246 cases. The most common reason providers ordered CCCP testing was for patients diagnosed with a treatment-resistant or recurrent tumor (n = 214; 61%). Findings were clinically impactful for 229 cases (64%). Molecular alterations that may inform future therapy in the event of progression or relapse were found in 42% of cases, and a targeted therapy was initiated in 23 cases (6.6%). The majority of tests were denied coverage by payers (n = 190; 77%). On average, insurers reimbursed 10.75% of the total NGS service charge. CCCP testing identified clinically impactful alterations in 64% of cases. Limited coverage and low reimbursement remain barriers, and broader reimbursement policies are needed to adopt pan-cancer NGS testing that benefits patients into clinical practice.

Pharmacogenomic Assessment of Patients with Colorectal Cancer and Potential Treatments.

Evolving intensiveness of colorectal cancer (CRC) treatment, including chemotherapeutics and targeted agents associations, in adjuvant and metastatic CRC (MCRC) settings, increased overall survival (OS) with individual variability of toxicity. Pharmacogenomic guidelines recommended pre-treatment identification of at-risk patients suggesting dose adjustment of fluoropyrimidines based on dihydropyrimidine dehydrogenase (DPYD), and irinotecan on UDP glucuronosyl-transferase 1 family polypeptide A1 (UGT1A1) genetic variants, but they are poorly applied in clinical practice. This review highlighted clinically validated pharmacogenetic markers, to underline the need of their implementation in the multidisciplinary molecular board for individual CRC patients in clinical practice. Five clinically relevant DPYD variants with different prevalence impair enzymatic effectiveness and significantly increase toxicity: c.1236 G>A (c.1129–5923 C>G, HapB3), 4.1–4.8%; c.1679 T>G (DPYD*13), c.1905+1G>A (DPYD*2A), c.2846 A>T, c.2194 A>T (DPYD*6) 1% each. c.1679T>G and c.1905+1G>A are most deleterious on DPD effectiveness, moderately reduced in c.1236/HapB3 and c.2846A>T. Cumulatively, these variants explain approximately half of the estimated 10–15% fluoropyrimidine-related gastrointestinal and hematological toxicities due to DPD. Prevalent UGT1A1 gene [TA]7TAA promoter allelic variant UGT1A1*28, characterized by an extra TA repeat, is associated with low transcriptional and reduced enzymatic effectiveness, decreased SN38 active irinotecan metabolite glucuronidation, vs wild-type UGT1A1*1 [A(TA)6TAA]. Homozygote UGT1A1*28 alleles patients are exposed to higher hematological and gastrointestinal toxicities, even more than heterozygote, at >150 mg/m2 dose. Dose reduction is recommended for homozygote variant. Wild-type UGT1A1*28 alleles patients could tolerate increased doses, potentially affecting favorable outcomes. Implementation of up-front evaluation of the five validated DPYD variants and UGT1A1*28 in the multidisciplinary molecular tumor board, also including CRC genetic characterization, addresses potential treatments with fluoropyrimidines and irinotecan associations at proper doses and schedules, particularly for early CRC, MCRC patients fit for intensive regimens or unfit for conventional regimens, requiring treatment modulations, and also for patients who experience severe, unexpected toxicities. Integration of individual evaluation of toxicity syndromes (TS), specifically limiting TS (LTS), an innovative indicator of toxicity burden in individual patients, may be useful to better evaluate relationships between pharmacogenomic analyses with safety profiles and clinical outcomes.

Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy

Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies. To implement a precision strategy, we initiated a multidisciplinary (basic/translational/clinical investigators, bioinformaticians, geneticists, and physicians from multiple specialties) molecular tumor board (MTB), which included a project manager to facilitate obtaining clinical-grade biomarkers (blood/tissue NGS, specific immunohistochemistry/RNA expression including for immune-biomarkers, per physician discretion) and medication-acquisition specialists/clinical trial coordinators/navigators to assist with medication access. The MTB comprehensively reviewed patient characteristics to develop N-of-One treatments implemented by the treating physician’s direction under the auspices of a master protocol. Overall, 265/429 therapy-evaluable patients (62%) were matched to ≥1 recommended drug. Eighty-six patients (20%) matched to all drugs recommended by MTB, including combinatorial approaches, while 38% received physician’s choice regimen, generally with unmatched approach/low degree of matching. Our results show that patients who receive MTB-recommended regimens (versus physician choice) have significantly longer progression-free (PFS) and overall survival (OS), and are better matched to therapy. High (≥50%) versus low (<50%) Matching Score therapy (roughly reflecting therapy matched to ≥50% versus <50% of alterations) independently correlates with longer PFS (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50–0.80; P < 0.001) and OS (HR, 0.67; 95% CI, 0.50–0.90; P = 0.007) and higher stable disease ≥6 months/partial/complete remission rate (52.1% versus 30.4% P < 0.001) (all multivariate). In conclusion, patients who receive MTB-based therapy are better matched to their genomic alterations, and the degree of matching is an independent predictor of improved oncologic outcomes including survival.

Abstract 2503: Molecular profiling of Taiwanese breast cancers reveals potential therapeutic targets: Preliminary results of 160 subjects

Abstract Introduction: Breast cancer is one of the leading causes of cancer-related death in women, and the annual incidence of breast cancer has continuously increased throughout the past two decades in Taiwan. There is a demand in developing an Asian-based genetic profiling database for breast cancer in improving the treatment response and recurrence rate. This study aimed to determine the difference of molecular alternations and identify the potential biomarkers regarding therapeutic target by analyzing the genetic profiling from a large cohort of breast cancer subjects using the method of next-generation sequencing (NGS). Materials and methods: The protocol consisted of three years enrollment and approximately four years follow-up after enrollment. Individual subject was assigned into Group 1 [planned to received surgery as first-line treatment and followed by adjuvant therapy, Group 2 [planned to receive neoadjuvant therapy as the first-line treatment and followed by surgery], and Group 3 [diagnosed with de novo and treatment naïve stage IV breast cancer, or stage IV breast cancer with recurrence beyond three years after surgery]. Molecular profiling and potential biomarkers were determined using Thermo FisherTM OncomineTM Comprehensive Assay version 3 (TMO comprehensive assay) from Formalin-Fixed Paraffin-Embedded (FFPE) tissues. Results: We presented the initial 160 subjects as preliminary results. The TMO comprehensive assay is a targeted, NGS assay that enables the detection of relevant SNVs, CNVs, gene fusions, and indels from 161 unique genes to help inform drug discovery research and clinical trial research programs such as the NCI-MATCH trial. Level of actionability of sequenced targets were evaluated with ESMO Scale of clinical actionability of molecular targets (ESCAT). Of note, Tier I [alteration-drug match associated with improved outcome in clinical trials], Tier II [antitumor activity associated with the matched alteration-drug but lack of prospective outcome data], and Tier III [matched drug-alteration that led to clinical benefit in another tumor type] matched targets including ERBB2 amplification, BRCA1/2 germline mutation, PIK3CA mutation, NTRK translocation (Tier I), PTEN loss, ESR1 mutation, AKT1 mutation, ERBB2 mutation (Tier II), and BRCA1/2 somatic mutation, MDM2 amplification, and ERBB3 mutation (Tier III) were retrieved and analyzed. 108 out of 160 sequenced subjects (67.5%) reported as least one variant (average 1.7 per case, ranged from 1 to 10). Two group 3 heavily pre-treated patients were identified to have all actionable genes varied. Ipatasertib, alpelisib, and talazoparib, for instance, had been advocated for the corresponding PTEN p.(Q219*), PIK3CA p.(G118S), and BRCA2 p.(Q1107*) mutations. Conclusion: Targeted sequencing of actionable genes is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancer patients. A valid scale of clinical actionability should be adopted for precision medicine practice under multidisciplinary molecular tumor board. Further details will be updated when more samples are ready for sequencing and actionability analyses in coming years. Citation Format: Chi-Cheng Huang, Chun-Yu Liu, Ling-Ming Tseng. Molecular profiling of Taiwanese breast cancers reveals potential therapeutic targets: Preliminary results of 160 subjects [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2503.

Abstract B07: Prospective germline next-generation sequencing in pediatric patients with neuroblastoma identifies frequent alterations in genes involved in DNA damage repair

Abstract Background: The role of germline ALK and PHOX2B variants in genetic predisposition to neuroblastoma (NB) is well established; however, alterations in genes associated with other syndromes, including RASopathies, Fanconi anemia, and Li-Fraumeni, have also been detected. Emerging data suggest potential roles for DNA damage repair (DDR) pathway genes in NB predisposition. The use of next-generation sequencing (NGS) technologies facilitates the unbiased detection of both known and novel germline variants. Methods: Patients (pts) with newly diagnosed and relapsed malignancies, including 43 NB pts, were referred to our institutional pediatric oncology NGS study to sequence germline DNA, tumor DNA, and RNA. Germline DNA was sequenced using a custom pediatric cancer panel (Agilent Sure Select capture technology) targeting 15,000 exons across 864 genes (1000x coverage). Variant pathogenicity was classified according to ACMG (American College of Medical Genetics and Genomics) criteria and evaluated at multidisciplinary molecular tumor boards. Rare variants of uncertain significance (VUS) with supportive corresponding somatic data, patient phenotypes, literature, and/or in-silico functional analyses were termed “Variants of uncertain significance with limited evidence for pathogenicity” (VUS-LEP). Results: Analyses have been completed for 41/43 enrolled NB pts. Patient history was retrospectively categorized as “high genetic predisposition risk” (HGPR) in 14/41 pts based on ≥1 of the following criteria: (1) family history of NB and/or significant family history of other cancer(s); (2) patient with NB and another metachronous or synchronous malignancy; (3) NB with congenital abnormalities; (4) multifocal NB. Germline pathogenic (P), likely pathogenic (LP) variants, or VUS-LEP in a known cancer predisposition gene were identified in 6/14 HGPR pts (43%), predominantly in DDR-related genes (PALB2, BRCA1/CHEK2, CHEK2/PALB2, NF1, DICER1, MITF). Of note, no ALK or PHOX2B germline variants were identified for the five pts with NB family history. For the 27 non-HGPR pts, germline P, LP variants or VUS-LEP in DDR genes were most prevalent and detected in 8/27 pts (30%), in genes such as BAP1, BARD1 (n=2), BLM, BRCA2, CHEK2, RAD51, RAD51D/NBN. In this non-HGPR population, we also identified a germline P TP53 variant (n=1), a LP FH variant (n=1) as well as additional germline VUS-LEPs in EZH2 (n=1) and ERCC2 (n=1). Conclusion: Prospective sequencing identified frequent germline variants in NB pts, predominantly in genes involved in DDR and homologous recombination, regardless of classification as HGPR. We intend to complete and report somatic characterization of the tumors, with a focus on mutational signatures and 11q loss encompassing ATM. Our findings may have implications for future targeted treatment recommendations (e.g., PARP inhibitors) as well as for appropriate genetic counseling for pts and families. Citation Format: Sarah Cohen-Gogo, Karin Langenberg-Ververgaert, Anita Villani, Winnie Lo, Ted Young, Nisha Kanwar, Scott Davidson, Nathaniel Anderson, Bailey Gallinger, Mehdi Layeghifard, Larissa Waldman, Daniel Morgenstern, Ledia Brunga, Stephen Meyn, David Malkin, Adam Shlien, Meredith Irwin. Prospective germline next-generation sequencing in pediatric patients with neuroblastoma identifies frequent alterations in genes involved in DNA damage repair [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B07.

Molecular matching and treatment strategies for advanced stage lung cancer at Dartmouth-Hitchcock Medical Center: A three-year review of a Molecular Tumor Board

Matching of actionable tumor mutations with targeted therapy increases response rates and prolongs survival in lung cancer patients. Drug development and trials targeting genetic alterations are expanding rapidly. We describe the role of a Molecular Tumor Board (MTB) in the design of molecularly informed treatment strategies in our lung cancer patient population.Tumor DNA was sequenced using a 50-gene targeted next-generation sequencing panel. Cases were evaluated by a multidisciplinary MTB who suggested a course of treatment based on each patient’s molecular findings.During a three-year period, 21 lung cancer patients were presented at the MTB. All patients lacked common activating EGFR mutations and ALK rearrangements. One patient had Stage IIIb disease; all others were Stage IV; 18 patients had received ≥1 prior line of therapy (range 0–5). Suggestions for treatment with a targeted therapy were made for 19/21 (90.5%) patients, and four patients (21%) underwent treatment with a targeted agent, two as part of a clinical trial. Identified barriers to treatment with targeted therapy included: ineligibility for clinical trials (n ​= ​2), lack of interest in study/distance to travel (n ​= ​2), lack of disease progression (n ​= ​2), poor performance status (n ​= ​5), decision to treat next with immunotherapy (n ​= ​3), and unknown (n ​= ​1).For the majority of lung cancer patients, the MTB provided recommendations based on tumor genetic profiles. Identified barriers to treatment suggest that presentation to the MTB at earlier stages of disease may increase the number of patients eligible for treatment with a genetically informed targeted agent.

Implementation and impact of the first two years of a systemwide molecular tumor board at Henry Ford Health System (HFHS).

e19266 Background: HFHS implemented clinically-oriented Precision Medicine Program (PMP) in 2016. As part of the program, multidisciplinary molecular tumor board (MTB) was created to review complex molecular cases, providing guidance to treating medical oncologist in selecting targeted therapies and clinical trials. In some cases MTB recommended genetic counseling or recommended against/for additional molecular testing. MTB consists of oncologists, molecular pathologists, clinical trial staff, and genetic counselors. MTB was designed as teaching platform engaging hematology-oncology fellows into cases analysis and presentation. Here we present preliminary analysis of the impact of the MTB on the HFHS oncology practice. Methods: From 09/08/2017 to 12/31/2019 MTB reviewed 120 cases, 116 cases were used for this analysis. Data was abstracted using Syapse precision oncology platform, MTB recommendation note, electronic medical record (EMR), and molecular test results. Results: Out of 116 pts 83 (72%) were Caucasian, 25 (22%) African American, 4 (3%) Asian, 1 (1%) American Indian. Fifty-two % (n = 21) had an ECOG performance status of 1. Most common primary disease sites were lung (39%, n = 45) brain (12%, n = 15), and hematologic cancers (9%; n = 10), followed by breast (5%, n = 6), prostate (4%, n = 5), colon (3%, n = 4), and others (28%, n = 31). The most common genetic abnormalities discussed were atypical EGFR (n = 15), non-V600 BRAF (n = 10), KRAS (n = 8), BRCA2 (n = 5), NF2 (n = 4), PTEN (n = 4), CSF3R (n = 3), IDH1 (n = 3), TP53 (n = 3), and 29 less common mutations. Thirty five (30%) pts out of 116 total were recommended clinical trials, although only 3 patients (10% of recommended) were enrolled into trials. 31 pts (27%) were recommended off-label therapy, although trials were preferred. 18% of pts (n = 21) were recommended genetics referral, although only 3 have seen Geneticist, with two undergoing germline testing. One pt was discovered to have a germline RET V804M mutation which was originally detected in the cancer. Conclusions: The first two years of data demonstrate the utility of the MTB and provide a basis for ongoing analysis. Through multidisciplinary approach, MTB encourages care coordination and collaboration. MTB resulted in genetics referrals, clinical trial recommendations, and identification of targeted therapy options, including off label. In many cases, MTB recommendations prevented futile therapies and/or additional molecular testing.

Clinical application of routine comprehensive tumour molecular profiling in the management of cancer patients

Abstract Background Along with the extension of the FDA approved molecular matched therapies, the evidence is building to support molecular profile-based off-label drug prescription or inclusion in a clinical trial. We report the findings from our real-world comprehensive molecular tumor profiling (CMTP) practice to assess how CMTP extends treatment options within and beyond standards of care. Methods Pts with a confirmed diagnosis of advanced cancers are eligible. DNA was extracted from either archival or fresh collected tumor samples. Blood plasma was used for sequencing if the tumor sample was unavailable. CMTP included next generation sequencing. A panel of 409, 50 or 17 genes was used based on multidisciplinary molecular tumor board (MMTB) recommendations. Additional tests (IHC, FISH, MSI testing) were performed if recommended by MMTB. Results 155 patients were eligible for the analysis (63% female, median age 57, range 17-90). Tumor types were gyneco (19%), colorectal (18%), lung (14%), pancreatic (10%), breast (9%), stomach (5%). A total of 94% actionable biomarker (AB) associated with potential benefit from approved therapy were identified across 68(44%) pts. 49 (72%) pts had only one AB while 19 had 2 or more AB (up to 5). The most common AB were BRCA1/2 mutation/deletion (14%), PIK3CA mutations (13%), PD-L1 overexpression (12.7%), microsatellite instability (11%) and ERBB2 mutation/amplification/overexpression (7%). 29/155 (19%) pts received in-label therapy recommendations (TR) (38% pts - lung, 31% pts – gyneco, 10% pts - colorectal). 28/126 (23%) pts without in-label TR received off-label TR (18% pts – gyneco, 18% pts colorectal, 14% pts – pancreatic, 10% pts – stomach) with a total of 56 TR (20% immunotherapy, 13% PARPi, 7% MEKi, 5% ERBB2i). 12/98 (12%) pts without in-label or off-label TR received profile-matched TR within a clinical trial. Across 19/155 (12%) pts we identified biomarkers associated with the resistance to standard therapy. Conclusions CMTP was informative for 72/155 (46%) pts. 69/155(44%) pts received TR. Across tumor types least % of pts received TR with prostate (0/5, 0%), pancreatic (4/15, 26%) and breast (5/14, 36%) cancer, suggesting the need to define pts population who may benefit from CMTP. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure V. Mileyko: Full / Part-time employment: Atlas Oncology Diagnostics, ltd. E. Veselovsky: Full / Part-time employment: Atlas Oncology Diagnostics, ltd. E. Rozhavskaya: Full / Part-time employment: Atlas Oncology Diagnostics, ltd. A. Kovtun: Full / Part-time employment: Atlas Oncology Diagnostics, ltd. M. Sharova: Full / Part-time employment: Atlas Oncology Diagnostics, ltd. M. Ivanov: Full / Part-time employment: Atlas Oncology Diagnostics, ltd. All other authors have declared no conflicts of interest.

Clinical outcome of personalised treatment guided by genome and transcriptome sequencing in patients with neuroendocrine neoplasms: Updated results from the German NCT/DKTK MASTER trial

Abstract Background Therapeutic options for neuroendocrine neoplasms (NEN) are limited, and only few NEN patients have been treated according to their individual genomic profile. We report the molecular and clinical characteristics of a large NEN cohort that was studied by prospective whole-genome (WGS), whole-exome (WES), and transcriptome sequencing (TS) within the NCT/DKTK MASTER precision oncology program. Methods Between 2013 and 2018, a total of 115 patients with advanced, heavily pretreated NEN were enrolled. Primary sites were gastrointestinal (n = 30), pancreatic/hepatic (n = 33), pulmonary (n = 20), genitourinary (n = 13), head/neck (n = 6), and other regions (n = 11). Grading according to the 2017 and 2019 WHO classification was neuroendocrine tumor (NET) G1, n = 12; NET G2, n = 31; NET G3, n = 12; neuroendocrine carcinoma, n = 36; mixed neuroendocrine-non-neuroendocrine neoplasm, n = 12; and other, n = 11. Results Of WES (n = 72) or WGS (n = 44) and TS (n = 92) were discussed in a multidisciplinary molecular tumor board. Recommendations were given in 103 cases (94%) for the following potential treatment alternatives: tyrosine or serine/threonine kinase inhibition (n = 67), PARP inhibition (n = 41), immunotherapy (n = 33), mTOR inhibition (n = 30), CDK4/6 inhibition (n = 19), MEK inhibition (n = 12), platinum-based chemotherapy (n = 7), BET inhibition (n = 7), anti-claudin18.2 (n = 5) or anti-DLL3 antibody treatment (n = 8). Somatic hypermutation (>10 mutations/megabase) was seen in 8.6% of patients. Treatment options could be implemented in 35 patients, of which 31 were evaluable for response: partial response, n = 10; mixed response, n = 1; stable disease, n = 11; progressive disease, n = 9; resulting in an overall response rate of 32% and a disease control rate of 71%. Conclusions Comprehensive genomic and transcriptomic characterization provides new insight into the molecular pathogenesis of NEN and creates therapeutic opportunities in a significant proportion of NEN patients who have exhausted standard treatment. Legal entity responsible for the study NCT Heidelberg & German Cancer Consortium. Funding German Cancer Research Center. Disclosure S. Kreutzfeldt: Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (self): Novartis; Research grant / Funding (institution): Roche; Travel / Accommodation / Expenses: Pfizer. C.E. Heilig: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (institution), Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Teva; Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.

EORTC SPECTA-AYA: A molecular profiling platform for adolescents and young adults with cancer in Europe

Abstract Background For most adolescent and young adult (AYA) cancers, age-specific molecular features are poorly understood. SPECTA, an academic translational research infrastructure for biomaterial collection and molecular analysis, will explicitly recruit AYA patients and will therefore collect empirical data to bridge the molecular gap between pediatric and adult oncology. Trial Design The initial pilot study, activated in February 2019 across Europe, will recruit 100 patients aged 12-29 years with newly diagnosed or relapsed high-grade gliomas and high-grade bone and soft tissue sarcomas. The primary objective of the pilot is to determine feasibility and recruitment rates. Formalin-fixed tumor tissue, whole blood and clinical data from study participants will be prospectively collected; the biomaterial will be stored centrally at the Integrated BioBank of Luxembourg (IBBL). Whole exome sequencing (WES) of matched tumor and blood, and tumor RNA sequencing and DNA methylation profiling will be performed at the German Cancer Research Center (DKFZ), Heidelberg. Virtual central pathology review of scanned diagnostic slides will be undertaken by an international expert panel, and diagnostic material returned to the participating centers. A multidisciplinary molecular tumor board will release a clinically validated report to referring clinicians within 4-6 weeks after biopsy. SPECTA-AYA constitutes a major opportunity to gain knowledge about the tumor biology of this unique age group. It incorporates notable innovative aspects: AYA specificity, pan-European academic collaboration, centralized biobanking, comprehensive molecular profiling, and virtual central pathology review, among others. SPECTA-AYA will help untangle the tumor particularities of AYAs with cancer and aims to improve their access to novel drugs and personalized medicine. Legal entity responsible for the study EORTC (European Organisation for Research and Treatment of Cancer). Funding Walgreens Boots Alliance. Disclosure W. Van der Graaf: Research grant / Funding (self): Novartis; Honoraria (institution), Advisory / Consultancy: Bayer. F. Bielle: Research grant / Funding (self), Shareholder / Stockholder / Stock options, Spouse / Financial dependant: Celgene; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Spouse / Financial dependant: Crossject; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Spouse / Financial dependant: Sanofi; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Spouse / Financial dependant: AbbVie. M. Preusser: Honoraria (self): Bayer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Honoraria (self): Gerson Lehrman Group (GLG); Honoraria (self): CMC Contrast; Honoraria (self): GlaxoSmithKline; Honoraria (self): Mundipharma; Honoraria (self): Roche; Honoraria (self): Astra Zeneca; Honoraria (self): AbbVie; Honoraria (self): Lilly; Honoraria (self): Medahead; Honoraria (self): Daiichi Sankyo; Honoraria (self): Merck Sharp & Dohme. S. Frohling: Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Pfizer. M.G. McCabe: Advisory / Consultancy: Ipsen Pharma. All other authors have declared no conflicts of interest.

1645P - Introducing standardized medical procedure and dynamic decision support program in precision oncology for the community of practice

BackgroundWhile increasing number of diagnostic laboratories perform new generation sequencing on tumor DNA at a rapidly decreasing cost, beyond companion diagnostics, multi-gene panels are still underutilized due to lack of reimbursement and value based technical assessment. Besides financial reasons, prioritizing between diagnostic tests, multiple genetic alterations and multiple on-label or off-label targeted treatment options linked to these alterations can be a major challenge without having a reproducible, standardized and effective information service system in hand that a molecular tumor board could safely rely on. Here, we present an easily clinically adaptable, dynamic treatment decision support program (Protocol), that makes tumor molecular profile-based oncology care feasible and potentially reimbursed by public insurance funds. MethodsOur Protocol was developed based on 4868 cancer cases with 429 different histology, 2367 genes with 36492 variants. Our program utilizes multidisciplinary molecular tumor board (MTB) supported by Realtime Oncology Treatment CalculatorTM (Calculator) with the idea of integrating molecular and clinical data to provide genomics-driven treatment strategy plan. MTB mobilizes multiple sub-specialties for managing patients and tumor samples. The Calculator under constant upgrade is currently operating based on 24000 rules, 4000+ curated evidence, 101 registered and 618 targeted drugs under development. ResultsThis medical procedure (protocol) was endorsed by the Hungarian National Health Insurance Fund based on QUALY gain calculation and value-based technology assessment. ConclusionsIt is crucial to have an established protocol in the community of practice to indicate effective and eliminate ineffective genomics-driven treatments based on molecular profiling. The technology assessment provided evidence that standardized decision support of the molecular tumor board (MTB) to select diagnostic tests and treatments can assure clinical utility and cost effectiveness of multigene testing (NGS). Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureI. Petak: Leadership role, ownership: Oncompass Medicine Hungary Ltd. C. Hegedus: Full / Part-time employment: Oncompass Medicine Hungary Ltd. E. Várkondi: Full / Part-time employment: Oncompass Medicine Hungary Ltd. Z. Farkas: Full / Part-time employment: Oncompass Medicine Hungary Ltd. D. Tihanyi: Full / Part-time employment: Oncompass Medicine Hungary Ltd. R. Dóczi: Full / Part-time employment: Oncompass Medicine Hungary Ltd. D. Mathiasz: Full / Part-time employment: Oncompass Medicine Hungary Ltd. G. Pajkos: Full / Part-time employment: Oncompass Medicine Hungary Ltd. R. Schwab: Advisory / Consultancy, ownership: Oncompass Medicine Hungary Ltd. J. Deri: Full / Part-time employment: Oncompass Medicine Hungary Ltd. All other authors have declared no conflicts of interest.

EORTC SPECTA-AYA: A unique molecular profiling platform for adolescents and young adults with cancer in Europe.

For most adolescent and young adult (AYA) cancers, age‐specific molecular features are poorly understood. EORTC‐SPECTA, an academic translational research infrastructure for biomaterial collection, will explicitly recruit AYA patients and will therefore collect empirical data to bridge the molecular gap between pediatric and adult oncology. The initial pilot study, activated in February 2019 across Europe, will recruit 100 AYA patients (aged 12–29 years) with newly diagnosed or relapsed high‐grade gliomas and high‐grade bone and soft tissue sarcomas. The primary objective of the pilot is to determine feasibility and recruitment rates. Formalin‐fixed tumor tissue and whole blood from study participants will be prospectively collected with clinical data and stored centrally at the Integrated BioBank of Luxembourg. Whole exome sequencing of matched tumor and blood, and tumor RNA sequencing and DNA methylation profiling will be performed at the German Cancer Research Center, Heidelberg, Germany. Virtual central pathology review of scanned diagnostic slides will be undertaken by an international expert panel, and diagnostic material returned to the participating centers. A multidisciplinary molecular tumor board will release a clinically validated report to referring clinicians within 4–6 weeks after biopsy. SPECTA‐AYA constitutes a major opportunity to gain knowledge about the tumor biology of this unique age group. It incorporates notable innovative aspects: AYA specificity, pan‐European academic collaboration, centralized biobanking, comprehensive molecular profiling and virtual central pathology review, among others. SPECTA‐AYA will help untangle the tumor particularities of AYAs with cancer and aims to improve their access to novel drugs and personalized medicine.

Mutational landscape of cervical cancer identified by prospective clinical sequencing in a nationwide cancer network.

e17022 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of cervical cancer (CC) patients assayed in a nationwide cancer network. Methods: 118 Pts with advanced CC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 47 years (range, 27-71), 69% were Caucasian. GA were identified in 88% (104/118) of CC, of which 87 (74%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most commonpresent in 73.5% (64/87) of CC. CRGA in other targetable pathways were identified: 24.1% (21/87) in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2), 9.1% (8/87) in HRD (BRCA1/2, ATM, PALB2, BRIP1) and 24.1% (21/87) in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). One patient was MSI-high and one patient was TMB-high. 29.8% (26/87) of CC patients were ordered a genomically-matched treatment, and 24 pts received treatment; 61.5% (16/26) were agents that were FDA approved in a different tumor type, and 34.6% (9/26) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The PFS for non study related patients was 7 weeks and OS was 19 weeks. Conclusions: In a large series of Cervical Cancer patients assayed with CGP, 27.5% (24/87) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

Mutational landscape of endometrial cancer identified by prospective clinical sequencing in a nationwide cancer network.

e17123 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of endometrial cancer (EC) patients assayed in a nationwide cancer network. Methods: 278 Pts with advanced EC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 59 years (range, 37-85), 58% were Caucasian. GA were identified in 97% (271/278) of EC, of which 218 (80%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most common, present in 63.8% of EC. CRGA in other targetable pathways were identified: 28.4% in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) , 12.5% in HRD (BRCA1/2, ATM, PALB2, BRIP1 ) and 9.9% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). 26 patients are MSI-high 9.5% (26/271) and 21 patients are TMB-high 7.7% (21/271). 29.8% (65/218) of EC patients were ordered a genomically-matched treatment, and 61 of these patients received the treatment. 69.2% (45/65) were agents that were FDA approved in a different tumor type, and 24.6% (16/65) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The median PFS for non-clinical trial study patients was 9 weeks, and the median OS was 27 weeks. Conclusions: In a large series of Endometrial and Uterine cancer patients assayed with CGP, 27.9% (61/218) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

Mutational landscape of ovarian cancers (OC) identified by prospective clinical sequencing in a nationwide cancer network.

e17067 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of OC assayed in a nationwide cancer network. Methods: 449 Pts with advanced OC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant (CR) GA were defined as associated with targeted therapies or mechanism-driven clinical trials. Treatment histories for the 449 patients were obtained with IRB-approved retrospective review. Results: Median age was 56 years (range, 23-83), 71% were Caucasian. GA were identified in 94% (420/449) of OC, of which 283 (63%) had a clinically relevant genomic alteration (CRGA). 24.0% in HRD ( BRCA1/2, ATM, PALB2, BRIP1). CRGA in other potentially targetable pathways were identified: 48.0% MEK pathway ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) CRGA, 33.5% PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7), and 10.6% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). All OC tested were microsatellite stable and only one patient had a tumor mutational burden &gt; 20 muts/Mb. 21% (59/283) of OC patients were ordered a genomically-matched treatment, 58% (37/64) were agents that were FDA approved in a different tumor type, and 17% (11/64) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. For the off label non-study population the median PFS was 19 weeks, and the median OS was 34 weeks. Conclusions: In a large series of OC assayed with CGP, 21% of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

Molecular Profiling of Hard-to-Treat Childhood and Adolescent Cancers

Little progress in pediatric cancer treatment has been noted in the past decade, urging the development of novel therapeutic strategies for adolescents and children with hard-to-treat cancers. Use of comprehensive molecular profiling in the clinical management of children and adolescents with cancer appears a suitable approach to improve patient care and outcomes, particularly for hard-to-treat cases. To assess the feasibility of identifying potentially actionable mutations using next-generation sequencing-based assays in a clinically relevant time frame. This diagnostic study reports the results of the TRICEPS study, a prospective genome sequencing study conducted in Québec, Canada. Participants, aged 18 years or younger at diagnosis, with refractory or relapsed childhood and adolescent cancers were enrolled from April 2014 through January 2018. Whole-exome sequencing (WES) of matched tumor normal samples and RNA sequencing of tumor were performed to identify single-nucleotide variants, fusion transcripts, differential gene expression, and copy number alterations. Results reviewed by a team of experts were further annotated, synthesized into a report, and subsequently discussed in a multidisciplinary molecular tumor board. Molecular profiling of pediatric patients with hard-to-treat cancer, identification of actionable and targetable alteration needed for the management of these patients, and proposition of targeted and personalized novel therapeutic strategies. A total of 84 patients with hard-to-treat cancers were included in the analysis. These patients had a mean (range) age of 10.1 (1-21) years and a similar proportion of male (45 [54%]) and female (39 [46%]). Sixty-two patients (74%) had suitable tissues for multimodal molecular profiling (WES and RNA sequencing). The process from DNA or RNA isolation to genomic sequencing and data analysis steps took a median (range) of 24 (4-41) days. Potentially actionable alterations were identified in 54 of 62 patients (87%). Actions were taken in 22 of 54 patients (41%), and 18 (33%) either were on a second or third line of treatment, were in remission, or had stable disease and thus no actions were taken. Incorporating genomic sequencing into the management of hard-to-treat childhood and adolescent cancers appeared feasible; molecular profiling may enable the identification of potentially actionable alterations with clinical implications for most patients, including targeted therapy and clinically relevant information of diagnostic, prognostic, and monitoring significance.

Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory or High-Risk Leukemias: A Report from the LEAP Consortium

▪Despite the remarkable pace of characterizing the genomics of pediatric acute leukemias, the integration of real-time sequencing results into clinical practice has lagged. With increased availability of molecularly-targeted therapies, the promise of matching genetic lesions in patients' leukemia cells to treatment has not yet been fully realized.We established the first pediatric leukemia clinical genomics consortium in the United States, known as the Leukemia Precision-based Therapy (LEAP) Consortium, which includes 13 major pediatric cancer institutions. We hypothesized that it is feasible to identify and match, in real-time, actionable alterations with a targeted therapy for pediatric patients with relapsed, refractory or high-risk leukemias or myelodysplastic syndrome (MDS). Using a combination of a DNA-based next-generation sequencing panel and RNA-based gene fusion testing, followed by data review by our multidisciplinary molecular tumor board, we are conducting a clinical trial to test this hypothesis.To date, we have enrolled and reviewed data from 143 patients stratified by disease status: Cohort 1, patients with relapsed or refractory leukemias (n=93), and Cohort 2, patients with de novo high-risk leukemias or MDS (n=50). A matched targeted therapy (MTT) recommendation has been made for 72% (n=103) of patients, tiered based on the level of evidence linking the mutation to potential activity of targeted therapy in the context of each patient's disease (Tier 1: 11%, Tier 2: 4%, Tier 3: 41%, Tier 4: 6%, Tier 5: 10%). Of the 44 patients in Cohort 1 with clinical follow-up data, 5 (11%) had alterations in therapy made based upon sequencing results and MTT recommendation. These include the use of the MEK inhibitor trametinib for RAS mutant acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) (n=2), dasatinib for B-ALL and T-ALL with NUP214-ABL1 translocations (n=2) and ponatinib for B-ALL with an ABL1 T315I mutation (n=1). In addition, this genomic data refined diagnosis and supported additional germline assessment in a subset of patients.In parallel to the genomic sequencing, we are conducting high-throughput drug sensitivity (HTS) assays to study in vitro anti-leukemia effects of a panel of up to 120 targeted inhibitors in the context of leukemia-associated genetic alterations. Of the initial 106 accrued patients, 40 (38%) had adequate amounts of blood or bone marrow for in vitro drug testing. All samples were tested in the inhibitor panel assay, and 65% of the samples yielded interpretable results. Inhibitor screening data was compiled for all 12 patients with genetic alterations resulting in Tier 1, 2 or 3 MTT recommendations. This subset of patients had leukemias with two distinct molecular profiles: 1) oncogenic RAS signaling pathway mutations or 2) oncogenic tyrosine kinase alterations. Our molecular tumor board recommended trametinib for the first group of patients and tyrosine kinase inhibitors (TKIs), specific to the mutation, for the second group of patients. In vitro HTS data analysis demonstrated dose-response sensitivity of leukemia cells with RAS pathway mutations to trametinib, many of which had half-maximal inhibitory concentration (IC50) less than 50 nM. Similarly, leukemia cells from patients with FLT3, ABL1 or KIT mutations generally showed dose-responses to relevant TKIs with low IC50s. Overall, HTS data were concordant with MTT recommendations informed by the sequencing results.This first in the US multi-institutional prospective leukemia genomics trial brings state-of-the-art clinical genetic testing, assessment of prognostic biomarkers, selection of patients for germline testing, and targeted therapeutic treatment recommendations to children and young adults with high-risk, relapsed or refractory leukemias or MDS. Our collaboration provides a unique opportunity to perform sophisticated patient-specific in vitro drug testing assays to impact MTT discovery efforts, which we plan to validate in vivo using patient-derived xenograft models where feasible. We believe that a model like the LEAP Consortium has the potential to transform precision medicine approaches for children with high-risk leukemias and to inform future genomics-guided therapeutic trials and drug discovery efforts. DisclosuresTasian:Aleta Biopharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Research Funding; Incyte Corporation: Research Funding. Burke:JAZZ: Speakers Bureau; Shire: Speakers Bureau; AMGEN: Speakers Bureau. Tyner:AstraZeneca: Research Funding; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Janssen: Research Funding; Array: Research Funding; Constellation: Research Funding; Gilead: Research Funding; Aptose: Research Funding; Incyte: Research Funding; Genentech: Research Funding.

P3.13-26 Outcomes of Patients with Metastatic Lung Cancer Presented in a Multidisciplinary Molecular Tumor Board

With the adoption of broad genomic profiling, interpretation of genomic data in NSCLC has become increasingly complex. Approved targeted therapies against oncogenic driver mutations have improved clinical outcomes for patients whose lung cancers harbor these genomic alterations. However, for other patients, the benefit of broad genomic sequencing is not fully proven. Multidisciplinary molecular tumor boards (MTB) may improve clinical outcomes by appropriately matching targeted treatments. We retrospectively reviewed clinical, pathologic, and molecular data of metastatic lung cancer patients presented at the UC Davis MTB from January 2016 through May 2017. Genomic alterations were identified by hybrid capture-based comprehensive genomic profiling to a median coverage depth of >500X for 315 cancer-related genes (FoundationOne®). Out of 48 patients presented, 19 (39.6%) had lung cancer. Fourteen patients (73.7%) had adenocarcinoma, 1 SCLC, 1 squamous, 2 neuroendocrine, and 1 mixed histology. Seventeen patients were available for follow-up. Median number of prior treatments was 2 (range: 0-7) and median number of prior targeted therapies was 2 (range: 0-5). On average, each tumor sample had 5.3 genomic alterations (range 2 – 14). Every sample had ³1 actionable mutation, in that matched targeted therapy was available in the form of an FDA-approved drug for NSCLC, FDA-approved drug in another tumor type, or genomically informed clinical trial. Tumors harbored an EGFR mutation (N=7), HER2 amplification (N=2), BRAF V600E (N=2), or mutation in BRCA1 (N=1), KIT (N=1), or PTCH1 (N=1). All 7 patients with an EGFR mutation had previously received EGFR-targeted therapy, six with progressive disease (PD) on prior EGFR-TKI. Thirteen patients (76.5%) received targeted therapy, including FDA-approved therapy for NSCLC (N=4), FDA-approved therapy for another tumor type (N=6), or a genomically informed clinical trial (N=3). The other four patients were either on an immunotherapy clinical trial (N=2) or could not tolerate treatment (N=2). Out of the 13 patients who received targeted therapy, 4 patients had a partial response (31%) (3 EGFR, 1 BRAF V600E), all other patients had stable disease or PD. Median PFS on MTB-selected treatment was 4.8 months (range: 25% 2.2 – 75% 10.7 months). MTB at an academic medical center matched a high percentage of patients to either a targeted treatment or clinical trials with targeted therapies or immunotherapy. A subset of patients had clinical benefit to targeted therapies in this pretreated population. Multidisciplinary expertise at MTB can guide treatment for NSCLC, but new targeted treatments are needed to improve clinical outcomes.