Nonsquamous Research Articles

1257MO ABBV-400, a c-Met protein-targeting antibody-drug conjugate (ADC), in patients (Pts) with advanced EGFR wildtype (WT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): Results from a phase I study

1257MO ABBV-400, a c-Met protein-targeting antibody-drug conjugate (ADC), in patients (Pts) with advanced EGFR wildtype (WT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): Results from a phase I study

1312P Datopotamab deruxtecan (Dato-DXd) vs docetaxel (DTX) in patients (pts) with advanced nonsquamous (NSQ) non-small cell lung cancer (NSCLC) with brain metastases (mets): Results from TROPION-Lung01

1312P Datopotamab deruxtecan (Dato-DXd) vs docetaxel (DTX) in patients (pts) with advanced nonsquamous (NSQ) non-small cell lung cancer (NSCLC) with brain metastases (mets): Results from TROPION-Lung01

Current status of PD-(L)1 inhibitor usage in advanced or metastatic non-small cell lung cancer: A national survey of oncologists in China.

e20559 Background: The aim of the present study conducted by Chinese Society of Clinical Oncology Expert Committee on Immunotherapy was to obtain real-world information on the use of PD-(L)1 inhibitors for non-small cell lung cancer (NSCLC) in different regions of China via a national questionnaire survey for oncologists. Methods: This survey was distributed online to cancer-related medical departments in 202 first-tier to fourth-tier cities of China between March to April 2023. The national survey consisted of four sections regarding oncologists’ concerns about immunotherapy as follows: treatment choice, response assessment, treatment duration, and management of immune-related adverse events (irAEs). Results: A total of 2,018 oncologists completed this survey. For advanced squamous (SQ) and non-squamous (NSQ) NSCLC without targetable genetic alterations, PD-(L)1 inhibitor-based regimens were the most widely used first-line treatment regimen (SQ: 52%, NSQ: 46%), followed by chemotherapy alone (SQ: 37%, NSQ: 37%) and other regimens (SQ: 11%, NSQ: 17%). The average treatment duration of 1L PD-(L)1 inhibitor-based regimens in SQ NSCLC and NSQ NSCLC were 6.4 and 6.2 cycles, respectively. 67% of oncologists may discontinue immunotherapy or change regimens when the first radiographic tumor assessment was SD per RECIST 1.1. Other reasons for early discontinuation of PD-(L)1 inhibitors before PD or unacceptable toxicity included economic reasons (78%) and patients’ low willingness to continue immunotherapy even they reached CR/PR (62%). Oncologists in the second-tier cities and below were more likely to discontinue immunotherapy when the tumors were stable, with shorter treatment duration of 5.7 cycles versus 7.1 cycles in the first-tier cities. The most common irAEs included dermatologic, endocrine, pulmonary, gastrointestinal, and hepatic toxicities. Conclusions: PD-(L)1 inhibitor-based regimens have become the priority choice for advanced NSCLC in China, however, the status of standardized continuous use of immunotherapy is obviously insufficient. There is a gap between clinical practice and clinical trials regarding PD-(L)1 inhibitor usage, which need more attention. [Table: see text]

TRITON: Phase 3b study of tremelimumab (T) + durvalumab (D) vs pembrolizumab (P), in combination with chemotherapy (CT), in non-squamous (NSQ) metastatic NSCLC (mNSCLC) with STK11and/or KEAP1 and/or KRAS mutations.

TPS8655 Background: Mutations in STK11 and KEAP1, present in approximately 20% and 15% of patients (pts) respectively with NSQ mNSCLC, lead to an immunosuppressive tumor microenvironment and are associated with inferior clinical outcomes with anti-PD-(L)1 based chemo-immunotherapy, especially when co-mutated with KRAS. Pts with tumors bearing STK11, KEAP1and/or KRAS mutations may benefit from combinations with CTLA-4 inhibitors, aimed at increasing immune responses. In the phase 3 POSEIDON trial (NCT03164616), first-line (1L) T+D+CT significantly improved overall survival (OS; HR 0.77 [95% CI 0.65–0.92]; P=0.0030) vs CT. These results were maintained after a median follow-up of >5 years. Subgroup analyses showed sustained OS improvement with T+D+CT vs CT in pts with mNSCLC with STK11 (NSQ), KEAP1(all histologies, due to small sample size), and KRAS (NSQ) mutations (HR [95% CI] 0.57 [0.32–1.04), 0.43 [0.16–1.25], and 0.55 [0.36–0.83], respectively). The TRITON study will further investigate the signal of efficacy observed in the POSEIDON subgroup analysis. The study will compare T+D+CT vs P+CT (a standard treatment for NSQ mNSCLC) in pts with STK11 and/or KEAP1 and/or KRASmutations. The results will help to inform clinical practice and to establish a biomarker-driven treatment strategy for these difficult-to-treat pts. Methods: TRITON (NCT06008093) is a phase 3b, multicenter, open-label, 2-arm parallel randomized study. Eligible pts, aged ≥18 years, must have NSQ mNSCLC (no EGFR or ALK alterations), with STK11, KEAP1, or KRAS mutations/co-mutations, no prior systemic therapy for mNSCLC, and ECOG performance status of 0/1. Approximately 280 pts will be randomized 1:1 to receive either T+D+CT or P+CT. In the T+D+CT arm, pts will receive T (75 mg) + D (1500 mg) + carboplatin (AUC 5 or 6)/cisplatin (75 mg/m2) + pemetrexed (500 mg/m2) every 3 weeks (Q3W) for 4 cycles (a fifth dose of T [75 mg] will be given in combination with D, post-platinum at week 16), followed by maintenance D (1500 mg) + pemetrexed (500 mg/m2) Q4W until disease progression (PD). In the P+CT arm, pts will receive P (200 mg) + carboplatin (AUC 5 or 6)/cisplatin (75 mg/m2) + pemetrexed (500 mg/m2) Q3W for 4 cycles, followed by maintenance P (200 mg) + pemetrexed (500 mg/m2) Q3W until PD, for up to 24 months. Randomization is stratified by mutation type ( KRAS [without STK11 or KEAP1] mutations are capped at 33% of the total sample) and tumor PD-L1 expression (≥1% vs <1%). Primary endpoints are OS in all pts and in the subset with STK11 or KEAP1 mutations/co-mutations. Key secondary endpoints include OS rates at 12 and 24 months, progression-free survival, objective response rate, duration of response (all RECIST v1.1; investigator-assessed) and safety/tolerability (CTCAE v5.0). Enrollment is ongoing. Clinical trial information: NCT06008093 .

Telisotuzumab vedotin monotherapy in patients with previously treated c-Met–overexpressing non-squamous EGFR wildtype advanced NSCLC: Primary analysis of the LUMINOSITY trial.

103 Background: Approximately 25% of patients (pts) with non-squamous (NSQ) EGFR wildtype (WT) NSCLC have c-Met protein overexpression (Ansell et al. 2022 CRUK), which is associated with a poor prognosis (Liang, Wang. Onco Targets Ther. 2020). Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody-drug conjugate comprising the mAb telisotuzumab and the microtubule polymerization inhibitor monomethyl auristatin E. The phase 2 LUMINOSITY trial (NCT03539536) aimed to identify the c-Met–overexpressing (OE) NSCLC population best suited to Teliso-V and expand selected group(s) for further evaluation of efficacy. We report on the primary analysis for pts with c-Met OE NSQ EGFRWT NSCLC. Methods: This phase 2, non-randomized, multicenter study enrolled pts with locally advanced/metastatic c-Met OE NSCLC, ≤2 prior lines of therapy (chemotherapy [CTx] + immunotherapy [IO] or sequential CTx + IO), and ≤1 line of chemotherapy. c-Met OE (Ventana MET [SP44] clinical trial assay [CTA]) was defined as ≥25% tumor cells with 3+ staining (high: ≥50% 3+; intermediate [int]: 25 to <50% 3+). Teliso-V was dosed at 1.9 mg/kg IV Q2W. Primary endpoint was overall response rate (ORR) by independent central review per RECIST v1.1. Results: 172 pts with NSQ EGFR WT NSCLC received ≥1 dose of Teliso-V and comprised the safety population; 161 (c-Met high, 78; c-Met int, 83) were included in baseline and efficacy analyses. Median age was 64 yrs (range 33–83), 69% were male, and 70% had ECOG PS 1. 97.5% had prior platinum and 82.0% had prior immune checkpoint inhibitor. Efficacy data are presented in Table below. ORR was 34.6% (c-Met high), 22.9% (c-Met int), 28.6% (overall). Median DOR was 9.0 mo (c-Met high), 7.2 mo (c-Met int), 8.3 mo (overall). Most common any-grade treatment-related AEs (TRAEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%). Grade 5 TRAEs occurred in 2 pts (interstitial lung disease, respiratory failure). Conclusions: Teliso-V has shown compelling and durable responses in pts with c-Met OE NSQ EGFR WT NSCLC, especially in pts with c-Met high. Teliso-V had an acceptable safety profile that was clinically manageable, which is consistent with previous data. Clinical trial information: NCT03539536 . [Table: see text]

ICARUS-LUNG01: A phase 2 study of datopotomab deruxtecan (Dato-DXd) in patients with previously treated advanced non-small cell lung cancer (NSCLC), with sequential tissue biopsies and biomarkers analysis to predict treatment outcome.

8501 Background: Few treatments with limited benefit are currently available after failure of targeted therapies, immunotherapy and platinum-based chemotherapy in patients (pts) with advanced NSCLC. Dato-DXd is an antibody-drug conjugate (ADC) composed of a TROP-2-directed monoclonal antibody linked to a topoisomerase I inhibitor via a peptide cleavable linker. In the phase 3 TROPION-Lung01 study, Dato-DXd demonstrated a statistically significant improvement of PFS over docetaxel in previously treated pts with advanced NSCLC. Here we report the results of ICARUS-Lung01 (NCT04940325), a multi-center, single-arm, phase 2 study evaluating activity, safety, and biomarkers of response/resistance to Dato-DXd in pretreated pts with advanced NSCLC. Methods: Intravenous Dato-DXd 6 mg/kg was given every 21 days to pts with advanced NSCLC, ECOG 0/1, who progressed on 1-3 lines of therapy (including actionable genomic alteration (AGA)-specific therapy if indicated). All pts underwent fresh tumor tissue biopsies at baseline, on-treatment (week 3 or 6) and end of treatment. Primary endpoint: investigator-assessed confirmed objective response rate (ORR). A set of translational analyses was performed to determine biomarkers associated with response/resistance, including TROP2 tumor membrane expression, TROP2-dynamics and spatial distribution (by AI-digital pathology), genomics, transcriptomic, spatial proteomics (by imaging mass cytometry) and CTCs. Results: A total of 100 pts received ≥1 dose: median age 60 years (26-83); 62% males, 89% smokers, 82% non-squamous (NSQ) histology, 23% AGA, median number of prior therapy lines 2 (1-5). At data cut-off (Dec 04, 2023), 92% discontinued therapy, 92 % had disease event, 67% died. Median treatment duration was 2.8 months (mos) (95%CI, 2.1-4.8), median follow-up 19.4 mos (95%CI, 18.2-20.4). Efficacy and safety results are shown in the table. Conclusions: In this heavily pretreated population, Dato-DXd showed similar efficacy and safety results to those reported in TROPION-Lung01. Patients with NSQ appeared to derive the greatest benefit. Translational analyses to determine biomarkers associated with response and/or resistance will be presented. Clinical trial information: NCT04940325 . [Table: see text]

Five-year outcomes with first-line (1L) nivolumab + ipilimumab + chemotherapy (N + I + C) vs C in patients (pts) with metastatic NSCLC (mNSCLC) in CheckMate 9LA.

8560 Background: InCheckMate 9LA (NCT03215706), 1L N + I + C demonstrated long-term, durable survival benefit vs C alone in pts with mNSCLC, regardless of tumor PD-L1 expression or histology. Here, we report updated efficacy and safety data with a 5-y follow up (f/u) and outcomes in 5-y survivors. Methods: Adults with stage IV or recurrent NSCLC, ECOG PS ≤ 1, and EGFR/ALK wild-type were randomized 1:1 to N 360 mg Q3W + I 1 mg/kg Q6W + C Q3W (2 cycles; n = 361) or C alone Q3W (4 cycles; n = 358). Maintenance pemetrexed was allowed for pts with non-squamous (NSQ) NSCLC (C arm only). Assessments were OS, PFS, ORR, DOR, treatment (tx)-free interval (TFI; time from last study tx dose to start of subsequent systemic tx or death), and safety. Exploratory analyses included quantifying the number of ipilimumab doses received by 5-y survivors, as well as PFS and TFI in these pts. Results: With a median f/u of 64.5 mo (database lock, 15 Dec 2023), clinical benefit continued to be seen with N + I + C vs C in all randomized pts (Table); 5-y OS rates were 18% vs 11%, respectively. Of pts treated with N + I + C, 11% were tx-free at 5 y. Clinical outcomes favored N + I + C vs C across tumor PD-L1 expression and histology subgroups (Table). In pts with tumor PD-L1 < 1%, 5-y OS and PFS rates with N + I + C were both ~3-fold higher than with C, and 5-y DOR rates were 25% vs 0% in the respective tx arms. Among pts who discontinued N + I + C due to tx-related adverse events (TRAEs; n = 61), 37% were alive at 5 y, and the TFI rate was 22%. In analyses of 5-y survivors, PFS favored N + I + C (n = 48) vs C (n = 30; HR, 0.52 [95% CI, 0.26–1.02]), and 5-y TFI rates were 72% vs 35%, respectively. Of 5-y survivors in the N + I + C arm, 21/48 (44%) received ≥ 17 doses of ipilimumab; of those who received < 17 doses, most had discontinued ipilimumab due to TRAEs. The extended f/u revealed no new safety signals. Conclusions: 1L N + I + C maintained long-term, durable survival benefit vs C in pts with mNSCLC at this 5-y f/u, particularly in pts with tumor PD-L1 expression < 1% or squamous (SQ) histology. N + I + C increased 5-y survivorship, with improved PFS and TFI in 5-y survivors over C. These data further underscore 1L N + I + C as an efficacious tx option for pts with mNSCLC. Clinical trial information: NCT03215706 . [Table: see text]

Molecular Diagnostics and Treatment Patterns in Metastatic Non-small Cell Lung Cancer Patients: Real World Evidence from Greece: LACHESIS Study.

Lung cancer, primarily non-small cell lung cancer (NSCLC), is the leading cause of cancer deaths globally. In Greece in 2020, 8,960 new cases were reported. NSCLC's 5-year survival rates range from 54% (stage I) to less than 2% (stage IV); however, innovative therapies like immune check points inhibitors (ICIs) and targeted treatments have notably enhanced outcomes. The aim of this study was to assess the 1st and 2nd line treatment patterns with the introduction of new treatment modalities. Additionally, we evaluated biomarker testing approaches in NSCLC. LACHESIS was a retrospective multinational study, collecting and analyzing data from adult patients from Russia, Bulgaria, and Greece with metastatic NSCLC either newly diagnosed or relapsed from earlier stages, who had the option to undergo biomarker testing (genetic alterations/programmed death-ligand 1 protein expression levels, PD-L1), and who received 1st line treatment for squamous (SQ) or non-squamous (N-SQ) NSCLC. Subsequent lines of therapy were also reported. The Greek site registered retrospective data from 250 NSCLC patients, of whom 206 were newly diagnosed (ND) metastatic NSCLC patients and 44 were patients relapsed from earlier stages. Seventy-two had SQ NSCLC and 169 had N-SQ NSCLC. For these patients, treatment patterns including immunotherapy±chemotherapy combinations were recorded. Biomarker testing patterns, including genetic alterations and PD-L1 expression levels were also documented. LACHESIS provides treatment patterns and biomarker testing data. Greek patients were treated according to international guidelines, with immunotherapy as a viable option, particularly for PD-L1 levels over 50%. Biomarker testing, crucial for non-squamous (N-SQ) cases, should yield timely results for driver mutations, prioritizing patient benefits.

First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden: A Population-based Real-world Study with Focus on Immunotherapy.

The treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) has evolved significantly since the introduction of immunotherapies. We here describe PD-L1 testing rates, treatment patterns, and real-world outcomes for PD-(L)1 inhibitors in Sweden. Data were obtained from the Swedish National Lung Cancer Registry for patients with advanced NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 who initiated first-line -systemic treatment from 01 April 2017 to 30 June 2020. PD-L1 testing was available in the registry from 01 January 2018. Kaplan-Meier was used for overall survival (OS) by type treatment and histology. A total of 2,204 patients with pathologically confirmed unresectable stage IIIB/C or IV NSCLC initiated first-line treatment, 1,807 (82%) with nonsquamous (NSQ) and 397 (18%) with SQ. Eighty-six per cent (NSQ) or 85% (SQ) had been tested for PD-L1 expression, a proportion that increased over time. The use of platinum-based therapy as first-line treatment decreased substantially over time while there was an upward trend for PD-(L)1-based therapy. Among patients with PS 0-1 initiating a first-line PD-(L)1 inhibitor monotherapy, the median OS was 18.6 and 13.3 months for NSQ and SQ NSCLC patients, respectively, while for the PD-(L)1 inhibitor and chemotherapy combination regimen, the median OS was 24.0 months for NSQ and not evaluable for SQ patients. The majority of advanced NSCLCs in Sweden were tested for PD-L1 expression. Real-world OS in patients with PS 0-1 receiving first-line PD-(L)1 inhibitor-based regimens was similar to what has been reported in pivotal clinical trials on PD-(L)1 inhibitors.

101 Real-world analysis of the impact of pemetrexed in first-line maintenance (1LM) with immunotherapy (IO) for non-squamous (NSQ) advanced/metastatic non-small cell lung cancer (a/mNSCLC) lacking targetable mutations, prior to and during the COVID-19 pandemic

101 Real-world analysis of the impact of pemetrexed in first-line maintenance (1LM) with immunotherapy (IO) for non-squamous (NSQ) advanced/metastatic non-small cell lung cancer (a/mNSCLC) lacking targetable mutations, prior to and during the COVID-19 pandemic

93P Real-world analysis of first-line maintenance (1LM) immunotherapy (IO) ± pemetrexed for non-squamous (NSQ) advanced/metastatic non-small cell lung cancer (a/mNSCLC) lacking targetable mutations, prior to and during the COVID-19 pandemic

93P Real-world analysis of first-line maintenance (1LM) immunotherapy (IO) ± pemetrexed for non-squamous (NSQ) advanced/metastatic non-small cell lung cancer (a/mNSCLC) lacking targetable mutations, prior to and during the COVID-19 pandemic

59P Datopotamab deruxtecan (Dato-DXd) in patients with previously treated advanced non-small cell lung cancer (NSCLC): Nonsquamous (NSQ) histology in the phase III TROPION-Lung01 trial

59P Datopotamab deruxtecan (Dato-DXd) in patients with previously treated advanced non-small cell lung cancer (NSCLC): Nonsquamous (NSQ) histology in the phase III TROPION-Lung01 trial

Epidemiology and Outcomes of Non–Small Cell Lung Cancer in South Korea

Valuable evidence regarding clinical characteristics, treatments, and outcomes for non-small cell lung cancer (NSCLC) is limited to individual hospital databases or national-level registries. The common data and federated analysis framework developed through the Extensible Platform for Observational Research in Lung Cancer (EXPLORE-LC) initiative allows for research across multiple high-quality data sources, which may provide a deeper understanding of the NSCLC landscape and identification of unmet needs of subpopulations. To describe clinical characteristics, initial treatment patterns, subsequent treatment, and overall survival (OS) of patients with NSCLC in South Korea. This multicenter cohort study included patients aged 18 years and older who were diagnosed with NSCLC between 2014 and 2019 and followed up until March 2020 at 3 tertiary hospitals in South Korea. Clinical data were collected using a common data model and clinical data warehouse. Patients who had an initial diagnosis of nonsquamous (NSQ) or squamous (SQ) NSCLC and who had received at least 1 treatment for NSCLC were included in the study. Data were analyzed from June through November 2022. The primary outcome was clinical OS for patients with NSCLC. Secondary outcomes were clinical characteristics and treatment patterns subsequent to the diagnosis of NSCLC. Among 22 101 patients with NSCLC who received anticancer treatment analyzed in this study, 17 350 patients (78.5%) had NSQ and 4751 patients (21.5%) had SQ NSCLC. Clinical characteristics and outcomes and treatment patterns were assessed for 13 084 patients with NSQ cancer who had known EGFR and ALK status (75.4%; mean [SD] 62.2 [10.5] years; 6552 males [50.1%]) and all 4751 patients with SQ cancer (mean [SD] age, 67.1 [8.6] years; 4427 males [93.2%]). More than half of patients with NSQ cancer were never smokers (7399 patients [56.6%]). Patients with SQ cancer were mostly males and former or current smokers (4235 patients [89.1%]) and were diagnosed at a later clinical stage than patients with NSQ cancer (eg, stage I: 1165 patients [24.5%] vs 5388 patients [41.2%]). Patients with EGFR-positive and ALK-positive NSQ cancer diagnosed between 2017 and 2019 had better median OS than similar patients diagnosed between 2014 and 2016 (EGFR-positive: not reached [95% CI, 35.9 months to not reached] vs 28.4 months [95% CI, 25.8 to 30.0 months]; P < .001; ALK-positive: not reached [95% CI, not reached] vs 49.5 months [95% CI, 35.1 months to not reached]; P < .001). No significant difference was observed in OS from first-line treatment for patients with SQ cancer. This study, which pooled medical data from multiple clinical data warehouses to produce a large study cohort, may provide meaningful insights into the clinical practice of NSCLC and underscores the value of a common data model approach. The analyzable dataset may hold great promise for future comprehensive identification of subpopulations and unmet needs.

Comparison of molecular testing rates and biomarker positivity by histology among patients (pts) with stage IV non-small cell lung cancer (NSCLC): A quality initiative by Integra Connect PrecisionQ.

582 Background: National Comprehensive Cancer Network guidelines for NSCLC recommend biomarker testing for EGFR, ALK, ROS1, BRAF, NTRK1/2/3, METex14 skipping, KRAS, RET, and ERBB2 (HER2) in advanced or metastatic NSCLC regardless of histology. We sought to understand the testing rates for these markers among pts with a squamous (S) histology compared to pts with a non-squamous (NS) histology, while also assessing positivity rates among pts based on histology by the respective biomarkers for pts with stage IV NSCLC. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 2 million cancer pts across 500 sites of care to assess testing rates and biomarker positivity rates based on histology among adult NSCLC patients. We included 3,889 Stage IV NSCLC pts, where we conducted chart reviews, investigating testing rates across each of the biomarkers based on patient histology (group 1). In addition, we evaluated 6,303 stage IV NSCLC pts, regardless of whether we conducted chart reviews, to assess rates of positivity among the respective biomarkers (group 2). Pts included in the analysis were diagnosed on or after 1/1/2019. We assessed rates of biomarker testing in group 1 and biomarker positivity (irrespective of the type of mutation) in group 2 stratified by histology. Descriptive analyses were used and proportions were compared using a two-tailed two-sample z-test. Results: Among the Group 1 stage IV pts in the comparison of tested vs. not-testedbased on histology (N= 3889), the average age was 72.9 (median = 75), 49% were female, 81.6% were NS. We found the testing rates among S pts (N=714) vs. NS (N=3175) as follows: EGFR-S 76% vs. EGFR-NS 92%, ALK-S 77% vs. ALK-NS 92%, BRAF-S 75% vs. BRAF-NS 87%, KRAS-S 71% vs. KRAS-NS 81%, MET-S 72% vs. MET-NS 80%, RET-S 72% vs. RET-NS 79%, ROS1-S 72% vs. ROS1-NS 79%, ERBB2-S 69% vs. ERBB2-NS 76%, and NTRK-S 62% vs. NTRK-NS 68%. All comparisons were statistically significant at P &lt; .01. Among the Group 2 stage IV pts who were tested(N = 6303), the average age was 72.6 (median = 73), 50.8% were female, 86.0% were NS. We found the positivity rates among S pts vs. NS pts as follows: EGFR-S 7.5% (N = 827) vs. EGFR-NS 19.5% (N = 4650), ALK -S 1.3% (N =837) vs. ALK-NS 3.6% (N = 5099), BRAF-S 2.8% (N = 742) vs. BRAF-NS 6.0% (N = 4399), KRAS-S 10.4% (N = 694) vs. KRAS-NS 31.1% (N=3763), MET-S 4.3 (N=645) vs. MET-NS 7.5% (N = 3537), RET-S 0.5% (N = 635) vs. RET-NS 1.4% (N= 3397), ROS1-S 0.6% (N = 629) vs. ROS1-NS 1.4% (N = 3346), ERBB2-S 2.2% (N = 504) vs. ERBB2-NS 3.8% (N = 2510), and NTRK-S 1.0% (N = 486) vs. NTRK-NS 1.5% (N = 2444). Conclusions: Our results indicate a need to increase biomarker testing among pts with S histology to be equivalent to those who were tested with a NS histology, as biomarker positivity rates present in pts with S histology warrant a molecular evaluation regardless of histology.

573P LUMINATE-103: Real-world treatment patterns and outcomes of patients (pts) with epidermal growth factor receptor mutant (EGFR MU), non-squamous (NSQ) locally advanced/metastatic non-small cell lung cancer (a/mNSCLC): Pooled analysis of large US electronic health record (EHR) datasets

573P LUMINATE-103: Real-world treatment patterns and outcomes of patients (pts) with epidermal growth factor receptor mutant (EGFR MU), non-squamous (NSQ) locally advanced/metastatic non-small cell lung cancer (a/mNSCLC): Pooled analysis of large US electronic health record (EHR) datasets

A Phase Ⅱ Study of Ubenimex Combined With Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non–Small-Cell Lung Cancer: TORG2241 (UBE-Q)

BackgroundAccording to the results of the KEYNOTE-407 trial, pembrolizumab plus platinum-based chemotherapy is the standard of care for patients with previously untreated advanced squamous non–small-cell lung cancer (NSCLC). Ubenimex, a potent aminopeptidase inhibitor, is an oral drug with immunostimulatory and antitumor activities. We aim to assess the safety and efficacy of ubenimex in combination with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. Patients and MethodsThis prospective, single-arm, multicenter, phase II clinical trial is conducted to confirm the tolerability and efficacy of the tested drugs. Patients with previously untreated advanced squamous NSCLC will receive a predetermined daily dose of ubenimex orally plus 4 cycles of pembrolizumab, nab-paclitaxel, and carboplatin, followed by continuous administration of ubenimex and pembrolizumab for a maximum of 2 years. To confirm tolerability, the daily dose of ubenimex will begin at level 1 (30 mg), which will be increased to levels 2 (60 mg) and 3 (120 mg) according to the escalation criteria, with a standard 3 + 3 design for achieving the target dose-limiting toxicity rate of 33%. The efficacy, safety, and tolerability of ubenimex at the determined dose level will be analyzed. The primary endpoint of the efficacy evaluation will be the objective response rate assessed by an independent review committee. ConclusionsThis is the first study to evaluate the efficacy and safety of ubenimex combined with pembrolizumab, nab-paclitaxel, and carboplatin in patients with previously untreated advanced squamous NSCLC. The results will help devise future treatment strategies.

Nivolumab after Induction Chemotherapy in Previously Treated Non-Small-Cell Lung Cancer Patients with Low PD-L1 Expression.

This study aimed to investigate whether cyclophosphamide (C) and adriamycin (A) induction therapy (IT) prior to nivolumab could enhance the efficacy of nivolumab in previously treated patients with non-squamous (NSQ) non-small-cell lung cancer (NSCLC) with less than 10% programmed death-ligand 1 (PD-L1) expression. Twenty-two enrolled patients received four cycles of CA-IT every 3 weeks. Nivolumab was given 360 mg every 3 weeks from the second cycle and 480 mg every 4 weeks after four cycles of CA-IT. The median progression-free survival (PFS) and overall survival (OS) were 2.4 months and 11.6 months, respectively. Fluorescence-activated cell sorting revealed the lowest ratio of myeloid-derived suppressor cells (MDSCs) to CD8+T-cells in the responders. Proteomic analysis identified a consistent upregulation of extracellular matrix-receptor interactions and phagosome pathways in the responders. Among the differentially expressed proteins, the transferrin receptor protein (TFRC) was higher in the responders before treatment (fold change > 1.2). TFRC validation with an independent cohort showed the prognostic significance of either OS or PFS in patients with low PD-L1 expression. In summary, CA-IT did not improve nivolumab efficacy in NSQ-NSCLCs with low PD-L1 expression; however, it induced decreasing MDSC, resulting in a durable response. Higher baseline TFRC levels predicted a favorable response to nivolumab in NSCLC with low PD-L1 expression.

Prevalence of actionable oncogenic alterations (AGA) among patients with advanced (adv) non-squamous (NSQ) non-small cell lung cancer (NSCLC) by age, sex, and race in the United States (US).

e21206 Background: Identification of AGA in NSCLC has improved the understanding of lung cancer pathogenesis and introduced targeted therapies directed against specific genomic alterations. Given the limited data on the prevalence of AGA by demographics, we evaluated prevalence of AGA by age at diagnosis (dx), sex, and race. Methods: A descriptive study used the US nationwide de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database. Eligible patients were adults with a dx of adv NSQ NSCLC from Jan-2016 to Sep-2020 who initiated a first line therapy. The prevalence of AGA for each age, sex, or race stratum was calculated. Results: The cohort included 3938 patients; 67.9% White, 52.9% female, and median age at dx was 68 y. Table 1 presents the prevalence of AGA. The prevalence of EGFR and BRAF V600E mutations increased with age at dx. ALK rearrangement and ROS1 fusion were more prevalent among patients &lt; 50 y vs ≥50 y while MET exon 14 skipping mutation was more prevalent among patients ≥75 y vs &lt; 75 y. EGFR and KRAS G12C mutations were more prevalent in female vs male. Compared to White or Black, Asians had a higher prevalence of EGFR mutations and lower prevalence of KRAS G12C. Conclusions: The prevalence of certain AGA among patients with adv NSCLC vary by demographics, which may contribute to disproportionate disease burden in certain strata. These results highlight the need to enhance diversity of clinical trial populations and ensure the disease burden across demographics in the general population are represented in clinical trials. [Table: see text]

Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non-Small Cell Lung Cancer: The Piedmont Study.

The Piedmont study is a prospectively designed retrospective evaluation of a new 48-gene antifolate response signature (AF-PRS) in patients with locally advanced/metastatic nonsquamous (NS) non-small cell lung cancer (NSCLC) treated with pemetrexed-containing platinum doublet chemotherapy (PMX-PDC). The study tested the hypothesis that AF-PRS identifies patients with NS-NSCLC who have a higher likelihood of responding positively to PMX-PDC. The goal was to gather clinical evidence supporting AF-PRS as a potential diagnostic test. Residual pretreatment FFPE tumor samples and clinical data were analyzed from 105 patients treated with first-line (1L) PMX-PDC. Ninety-five patients had sufficient RNA sequencing (RNA-seq) data quality and clinical annotation for inclusion in the analysis. Associations between AF-PRS status and associate genes and outcome measures including progression-free survival (PFS) and clinical response were evaluated. Overall, 53% of patients were AF-PRS(+), which was associated with extended PFS, but not overall survival, versus AF-PRS(-) (16.6 months vs. 6.6 months; P = 0.025). In patients who were stage I to III patients at the time of treatment, PFS was further extended in AF-PRS(+) versus AF-PRS(-) (36.2 months vs. 9.3 months; P = 0.03). Complete response (CR) to therapy was noted in 14 of 95 patients. AF-PRS(+) preferentially selected a majority (79%) of CRs, which were evenly split between patients stage I to III (six of seven) and stage IV (five of seven) at the time of treatment. AF-PRS identified a significant population of patients with extended PFS and/or clinical response following PMX-PDC treatment. AF-PRS may be a useful diagnostic test for patients indicated for systemic chemotherapy, especially when determining the optimal PDC regimen for locally advanced disease.

A Phase I/II Study of Necitumumab Plus Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non–Small Cell Lung Cancer Study: (NEJ048A/NEXUS)

BackgroundPlatinum-based combination therapy plus a programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitor is a standard treatment for patients with stage IV non–small cell lung cancer. However, necitumumab is used with gemcitabine and cisplatin as a first-line treatment option for squamous cell lung cancer (SqCLC). Furthermore, the combination of necitumumab with immune checkpoint inhibitors has the potential to enhance tumor immunity and improve the therapeutic effect. Thus, we planned and initiated this phase I/II study to evaluate the safety and efficacy of necitumumab plus pembrolizumab, nanoparticle albumin–bound (nab)-paclitaxel), and carboplatin therapy for patients with previously untreated SqCLC. Patients and MethodsIn phase I, the primary endpoint is the tolerability and recommended dose of necitumumab combined with pembrolizumab plus nab-paclitaxel and carboplatin. In phase II, the primary endpoint is the overall response rate. Secondary endpoints are disease control rate, progression-free survival, overall survival, and safety. Forty-two patients will be enrolled in phase II. ConclusionThis is the first study to investigate the efficacy and safety of necitumumab plus pembrolizumab combined with platinum-based chemotherapy in patients with previously untreated SqCLC.