Targeted Agent And Profiling Utilization Registry Research Articles

Abstract CT268: Palbociclib (P) in patients (pts) with solid tumors with CCND1 amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Abstract Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with CCND1 amp or mut treated with P are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Recommended dosing was one 125 mg capsule taken orally once daily for 21 days followed by 7 days off, until disease progression. Low accruing histology-specific cohorts with CCND1 amp or mut were collapsed into a histology-pooled cohort for analysis. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial response (PR) or stable disease (SD) of at least 16 weeks (wks) duration (SD16+) per RECIST v1.1. The hypothesized null DC rate of 15% was rejected if the lower limit of a 1-sided 90% CI was >15%. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response (OR), duration of response (DOR) and SD, and safety. Results: 38 pts with 16 tumor types with CCND1 amp (n=36), mut (n=1) or both (n=1) were enrolled. 2 pts left before the 8-wk post-baseline tumor evaluation and were unevaluable for efficacy. Table shows demographics, outcomes and toxicity. 1 pt with CR (melanoma, PTEN Y155fs comutation, DOR= 111 wks), 1 with PR (melanoma, DOR= 9 wks) and 4 with SD16+ (prostate [2], bladder, bile duct) were observed for DC rate of 17% (1-sided 90% CI: 9 to 100) and OR rate of 6% (95% CI: <1 to 19). The null DC rate was not rejected. All pts with DC had CCND1 amp. 14 pts had ≥1 grade 3-4 tx-related adverse event (AE) or serious AE (SAE). Conclusions: P did not meet prespecified criteria for demonstrating activity in pts with solid tumors with CCND1 amp or mut. Table 1. Demographics (N=38); Efficacy Outcomes (n=36); Toxicity Outcomes (N=38) Median (Med) age, years (range) 66 (38-83) Female, No. (%) 15 (40) ECOG PS, No. (%) 0 9 (24) 1 23 (61) 2 6 (16) Prior systemic regimens, No. (%) 1 3 (8) 2 11 (29) ≥3 24 (63) Most common tumor types, No. (%) Head and neck 7 (18) Melanoma 5 (13) Esophageal 4 (11) Prostate 4 (11) Endometrial 4 (11) DC rate, % (OR and SD16+) (1-sided 90% CI) 17 (9, 100) OR rate, % (95% CI) 6 (<1, 19) Med PFS, wks (95% CI) 8 (6, 8) Med OS, wks (95% CI) 20 (15, 31) Med DOR (range), wks, n=2 9 and 111 Med duration of SD for pts with SD16+ (range), wks, n=4 33 (28, 48) Number of pts2 (%) with tx-related AE or SAEs AE3 14 (37) SAE4 4 (11) 1 Percentages may be >100% due to rounding2 Patients may have experienced one or more events3 Anemia, AST increase, lymphopenia, neutropenia, thrombocytopenia, leukopenia4 Febrile neutropenia, hyponatremia, neutropenia, thrombocytopenia Citation Format: Ramya Thota, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Tareq Al Baghdadi, Evan Pisick, Olatunji B. Alese, Herbert L. Duvivier, Ajjai S. Alva, Apar Kishor Ganti, Raghava R. Induru, Apostolia M. Tsimberidou, Mehmet Akce, Navid Hafez, Evthokia Hobbs, Andrew Riddle, Margaret von Mehren, Gina N. Grantham, Abigail Gregory, Dominique C. Hinshaw, Susan Halabi, Richard L. Schilsky. Palbociclib (P) in patients (pts) with solid tumors with CCND1 amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT268.

Abstract CT267: Temsirolimus (T) in patients (pts) with solid tumors with AKT1/3 amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Abstract Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with AKT1/3 amp or mut treated with T are reported. Methods: Eligible pts had solid tumors, measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. After antihistamine pretreatment, 25 mg T was infused over 30-60 minutes once weekly until disease progression. Low accruing histology-specific cohorts with AKT1/3 amp or mut were collapsed into 1 histology-pooled cohort for analysis. Primary endpoint was disease control (DC) per investigator defined as complete or partial response or stable disease (SD) of at least 16 weeks (wks) duration (SD16+) per RECIST v1.1. The hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test with α= 0.10. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response (OR), duration of SD, and safety. Results: 28 pts with solid tumors (14 tumor types; 13 pts had breast, ovarian or endometrial tumors) with AKT1 mut (n=25), AKT1 amp (n=1), both AKT1 amp and mut (n=1), or AKT3 amp (n=1) were enrolled. All pts were evaluable for efficacy. Table shows demographics, outcomes and toxicity. 4 pts with SD16+ (lung, breast, endometrial and ossifying fibromyxoid tumor) were observed for a DC rate of 14% (1-sided 90% CI: 6 to 100) and an OR rate of 0% (95% CI: 0 to 12). The null DC rate was not rejected (p=0.62). All 4 pts with DC had an AKT1 E17K mut. 5 pts had ≥1 grade 3 adverse events (AE) or serious AEs (SAE) at least possibly related to T. Conclusions: T did not meet TAPUR’s prespecified criteria to declare a signal of activity in pts with solid tumors with AKT1/3 mut or amp. Table 1. Demographics, Efficacy Outcomes, and Toxicity Outcomes (N=28) Median (Med) age, years (range) 66 (39-83) Female, No. (%) 22 (79) ECOG PS, No. (%) 0 12 (43) 1 12 (43) 2 4 (14) Prior systemic regimens, No. (%) 1 2 (7) 2 6 (21) ≥3 20 (71) DC rate, % (OR and SD16+) (1-sided 90% CI) 14 (6, 100) OR rate, % (95% CI) 0 (0, 12) Med PFS, wks (95% CI) 8 (6, 8) Med OS, wks (95% CI) 25 (14, 31) Med duration SD for patients with SD16+ (range), wks (n=4) 26 (18, 40) Number of pts2 (%) with tx-related AE or SAE (all grade 3) AE3 5 (18) SAE4 3 (11) 1 Percentages may be >100% due to rounding2 Pts may have experienced one or more events3 Lymphocyte count decrease and oral mucositis4 Anorexia, fatigue, pericardial effusion, thromboembolic event Citation Format: Deepti Behl, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Niklas Mackler, Herbert L. Duvivier, Philip J. Gold, Sapna R. Patel, Regan M. Duffy, Lauren A. Mauro, Eugene R. Ahn, Maria Bell, Carmen J. Calfa, Jean L. Grem, Jens Rueter, Margaret von Mehren, Gina N. Grantham, Abigail Gregory, Dominique C. Hinshaw, Susan Halabi, Richard L. Schilsky. Temsirolimus (T) in patients (pts) with solid tumors with AKT1/3 amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT267.

Regorafenib in Patients With Solid Tumors With BRAF Alterations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

PURPOSE Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with BRAF alterations treated with regorafenib are reported. METHODS Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-1, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as investigator assessment of patients with complete or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low accruing histology-specific cohorts with BRAF alterations treated with regorafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, 0.84; α, .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS Twenty-eight patients with 12 tumor types with BRAF alterations were enrolled from June 2016 to June 2021. All patients were evaluable for efficacy. Two patients with PR and four with SD16+ were observed for DC and OR rates of 21% (90% CI, 12 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected ( P = .24). Eight patients had at least one grade 3 adverse event or serious adverse event at least possibly related to regorafenib. CONCLUSION Regorafenib did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with BRAF alterations.

Concordance in Molecular Tumor Board Case Reviews in the ASCO TAPUR Study.

With the advent of precision medicine, molecular tumor boards (MTBs) were established to interpret genomic results and guide decision making for targeted therapy in oncology patients. There are currently no universal guidelines for how MTBs should operate and thus variance can be seen depending on which MTB is reviewing the case. This study assesses the concordance of MTB recommendations when a participant case is reviewed by two different MTBs, establishes potential reasons for discordance, and advocates for the establishment of standard MTB operating guidelines. Participants with advanced cancer, who had exhausted all standard treatment options were screened for the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. Cases were submitted for MTB review if the treatment proposal was outside the protocol genomic matching rules, or if multiple treatment options were identified. Of the 306 cases submitted for review by the TAPUR MTB from 2016 to 2018, 107 were randomly selected for secondary review by a different MTB group. Recommendations from the original review were not disclosed. Concordance between MTB group recommendations was assessed. Concordance was defined as agreement between MTB reviews on the genomic alteration and study drug match proposed by the clinical site. Thematic qualitative analysis was conducted for the discordant cases to assess reasons for discordance. Complete or partial concordance was observed in 79% of cases (95% CI, 70 to 86; one-sided P = .25). Most discordant analyses were due to disagreements on the strength of evidence regarding efficacy of the proposed treatment (32%). When presented with identical participant cases, different MTB review groups make the same or similar treatment recommendations approximately 80% of the time.

Olaparib in Patients With Pancreatic Cancer With BRCA1/2 Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study

PURPOSE Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with advanced pancreatic cancer with BRCA1/ 2 mutations treated with olaparib are reported. METHODS Eligible patients had advanced pancreatic cancer, measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options available. Genomic testing was performed in Clinical Laboratory Improvement Amendments–certified, College of American Pathologists-accredited site selected laboratories. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16 weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of stable disease, and safety. RESULTS Thirty patients with BRCA1/ 2 mutations were enrolled from November 2016 to August 2019. The median number of reported previous therapies was 3 (range, 1-10). Two patients were not evaluable and excluded from efficacy analyses. Two patients with complete response, three with partial response and three with SD16+, were observed for DC and OR rates of 31% (90% CI, 18 to 40; P = .04) and 18% (95% CI, 6 to 37), respectively. The median PFS was 8 (95% CI, 8 to 15) weeks, and the median OS was 38 (95% CI, 21 to 65) weeks. Three patients had at least one drug-related grade 3 adverse event or serious adverse event of anemia, fever, or oral mucositis. CONCLUSION Olaparib showed antitumor activity in patients with advanced pancreatic cancer with BRCA1/ 2 mutations extending findings of recent studies of olaparib in patients with this disease.

Talazoparib (Tala) in patients (pts) with colorectal cancer (CRC) with BRCA1/2 mutations (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

106 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with CRC with BRCA1/2 mut treated with Tala are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received 1 mg of Tala orally daily until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete or partial response or stable disease of at least 16 weeks (wks) duration (SD16+) per RECIST v 1.1. Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled; otherwise, the cohort is closed. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), and safety. Results: 10 pts with advanced CRC and BRCA1 mut (n=3), BRCA2 mut (n=5), or both (n=2) were enrolled from February 2020 to June 2021. Germline or somatic status was not reported in 7 of 10 pts, 2 pts had somatic BRCA2 muts and 1 pt had a germline BRCA2 mut. 2 pts had left sided tumors, 2 had right sided, 3 had rectal tumors, and 3 pts had tumors that were site undetermined. All pts were evaluable for efficacy and toxicity. Table summarizes pt demographics and outcomes. No pts experienced DC, median PFS was 8 wks (95% CI, 6 to 8) and median OS was 24 wks (95% CI, 7 to 43). Co-alterations were observed in the following genes: KRAS (3 pts) and BRAF (2 pts). 2 pts had 3 separate grade 3 adverse events of anemia or fatigue at least possibly related to Tala. Conclusions: Monotherapy Tala did not demonstrate sufficient clinical activity in pts with advanced CRC with BRCA1/2 mut. Other tx should be considered for these pts, including tx offered in clinical trials. Clinical trial information: NCT02693535 . [Table: see text]

Abemaciclib in patients (pts) with esophageal cancer (EC) with CDKN2A loss or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

308 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with EC with CDKN2A loss or mut treated with abemaciclib are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received 200 mg (four 50 mg tablets) of abemaciclib twice daily for a total daily dose of 400 mg until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete or partial (PR) response per RECIST v. 1.1, or stable disease of at least 16 weeks (wks) duration (SD16+). Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled; otherwise, the cohort is closed. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. DOR is defined as time from pt’s first documented OR to progressive disease. Results: 10 pts with EC (8 adenocarcinoma, 2 squamous) and CDKN2A loss (n=5) or CDKN2A mut (n=5) were enrolled from Dec 2019 to June 2022. 6 pts had HER2 negative EC, 1 pt had HER2 low EC, 1 pt had HER2 positive EC, and 2 pts were not tested for HER2. All pts were evaluable for efficacy and toxicity. Table summarizes pt demographics and outcomes. 1 pt with CDKN2A loss had a 27-wk PR for a DC rate of 10% (1-sided 90% CI, 1% to 100%) and OR rate of 10% (95% CI, <1% to 45%). The null DC rate was not rejected (p=0.80). Median PFS was 8 wks (95% CI, 2 to 13) and median OS was 17 wks (95% CI, 9 to 35). The pt with PR had HER2 negative adenocarcinoma, ECOG PS of 1 and 2 prior lines of therapy. 4 pts had 12 serious adverse events at least possibly related to tx, including anemia, atrial fibrillation, increased creatinine, dehydration, dyspnea, generalized muscle weakness, heart failure, lung infection, pericardial effusion and thrombocytopenia. 4 pts had a drug-related grade 3 AEs including anemia, increased bilirubin and thrombocytopenia. Conclusions: Abemaciclib monotherapy did not demonstrate sufficient clinical activity in pts with advanced EC with CDKN2A loss or mut for continued evaluation in this pt population. Other tx should be considered for these pts, including tx offered in clinical trials. Clinical trial information: NCT02693535 . [Table: see text]

207P Palbociclib (P) in patients (pts) with solid tumors with CDK4 or CDK6 amplification (amp): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study

207P Palbociclib (P) in patients (pts) with solid tumors with CDK4 or CDK6 amplification (amp): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study

Nivolumab Plus Ipilimumab in Patients With Solid Tumors With ATM Mutations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with ATM mutations treated with nivolumab plus ipilimumab are reported. Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Primary end point was disease control (DC), defined as complete (CR) or partial (PR) response or stable disease (SD) of at least 16 weeks duration (SD16+). Low-accruing histology-specific cohorts with ATM mutations treated with nivolumab plus ipilimumab were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated based on a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = .84; α = .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of SD, and safety. Twenty-nine patients with 10 tumor types with ATM mutations were enrolled from January 2018 to May 2020. One patient was not evaluable for efficacy. One CR, three PR, and three SD16+ were observed for DC and OR rates of 24% (P = .13; one-sided 90% CI: 14 to 100) and 14% (95% CI: 4 to 32), respectively. The null hypothesis of 15% DC rate was not rejected. Eleven patients had one treatment-related grade 3 adverse event (AE) or serious AE. There were two treatment-related patient deaths including immune-related encephalitis and respiratory failure. Nivolumab plus ipilimumab did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with ATM mutations.

Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study.

The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a pragmatic basket trial evaluating antitumor activity of approved targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from cohorts of patients with high tumor mutational burden (HTMB, defined as ≥9 mutations per megabase) with advanced colorectal cancer (CRC) and other advanced cancers treated with pembrolizumab are reported. Eligible patients were 18 years and older with measurable tumors and a lack of standard treatment options, an Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. The primary end point was disease control (DC), defined as complete or partial response or stable disease (SD) of at least 16-weeks duration. For the CRC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. Low accruing histology-specific cohorts were collapsed into one histology-pooled (HP) cohort. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included objective response (OR), safety, progression-free survival, overall survival, duration of response, and duration of SD. Seventy-seven patients with HTMB with CRC (n = 28) or advanced cancers (n = 49) were treated with pembrolizumab. For the CRC cohort, the DC rate was 31% (P = .04) and the OR rate was 11%. For the HP cohort, the DC rate was 45% (one-sided 90% CI, 35 to 100) and the OR rate was 26%. The null hypothesis of a 15% DC rate was rejected for both cohorts. Twelve of 77 patients experienced treatment-related grade 3 adverse events (AEs) or serious AEs, including two deaths. Pembrolizumab demonstrated antitumor activity in pretreated patients with advanced cancers and HTMB.

Talazoparib (Tala) in patients (pts) with solid tumors with BRCA1/2 mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

3115 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with BRCA1/2 mut treated with Tala are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received 1 mg of Tala orally daily until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial (PR) response or stable disease (SD) of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. The hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test (alpha 0.10; 82% power). Secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR) and SD, and safety. DOR is defined as time from pt’s first documented objective response (OR) to progressive disease (PD). Duration of SD is defined as time from tx start to PD. Results: 28 pts with 16 solid tumors (6/28 pts had lung cancer) with BRCA1 (n=9) , BRCA2 (n=16) , or BRCA1/2 (n=3) mut were enrolled from Dec 2019 to Sept 2021. All pts were included in efficacy analyses. Demographics and outcomes are shown. 1 CR, 9 PR and 6 SD16+ were observed for a DC rate of 57% (1-sided 90% CI: 43% to 100%) and an OR rate of 36% (95% CI: 19% to 56%); the null hypothesis of a 15% DC rate was rejected (p<0.001). 11/16 pts with OR or SD16+ had a BRCA2 mut, 4 had BRCA1 mut, and 1 had both. The pt with a CR (duration of 93 wks) had non-melanoma skin cancer, with BRCA2 and ATM muts, and was microsatellite instability high with 41 muts per megabase. Pts with PR had various solid tumors; 6/9 pts had BRCA2 mut, 2 had BRCA1 mut , 1 had both. Of pts with DC, 11 had tumor types for which PARP inhibitors are not yet FDA approved. Median duration of PR was 20 wks (range, 11-80). 10/16 pts with DC had a co-alteration in the 24 homologous recombination-related genes examined, mainly ATM (3) or ARID1A (2). 13 pts had ≥1 grade 3 tx-related adverse or serious adverse events including: anemia, AST or bilirubin increase, hyponatremia, nausea, vomiting, neutrophil, platelet, or white blood cell decrease. Conclusions: Tala demonstrated antitumor activity in heavily pretreated pts with advanced solid tumors with BRCA1/2 mut. Additional study is warranted to confirm the efficacy of Tala in non-breast, non-ovarian cancer pts with BRCA1/2 mut. Clinical trial information: NCT02693535 . [Table: see text]

Nivolumab plus ipilimumab (N+I) in patients (pts) with ovarian cancer (OC) with BRCA1/2 mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

5548 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pts with OC with BRCA1/2 mut treated with N+I are reported. Methods: Eligible pts had advanced OC, measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was done in CLIA-certified, CAP-accredited labs. PD-L1 status was not routinely reported. Pts received I at 3 mg/kg every 3 wks for 4 doses with N at 1 mg/kg IV every 3 weeks (wks) for 4 doses. N alone was then continued at 240 mg every 2 wks or 480 mg every 4 wks until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete or partial (PR) response per RECIST v. 1.1, or stable disease of at least 16+ wks duration (SD16+). CA-125 levels were not routinely reported. Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled; otherwise, the cohort is closed. If ≥7 of 28 pts have DC, the null DC rate is rejected. P-value calculated based on 2-stage design. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: 33 pts with OC and BRCA1 (n=20), BRCA2 (n=10), or both mut (n=3) were enrolled from Sept 2017 to Oct 2019. 6 pts were not evaluable for efficacy analysis; 1 pt was found to be ineligible after enrolling, 5 pts discontinued tx before the post-baseline tumor evaluation due to an adverse or serious adverse event (SAE). Table shows demographics and efficacy outcomes. 6 pts with PR were observed for an OR rate of 22% (95% CI: 9% to 42%) and a DC rate of 27% (90% CI: 13% to 36%); the null hypothesis of a 15% DC rate was not rejected (p=0.17). 3 pts with PR had BRCA1 mut only, 2 pts had BRCA2 mut only and 1 pt had both BRCA1 and BRCA2 mut. Of the 6 pts with PR, 4 had microsatellite (MS) stable (MSS) tumors and MS status was not reported in 2. Of the 4 with MSS, 3 had a tumor mutational burden (TMB) ≤ 10 mutations per megabase and 1 had TMB of 11. 11 pts had at least 1 tx-related SAE, including acute kidney injury, ALT/AST increase, colitis, dehydration, diarrhea, E. coli, electrolyte disorder, fever, nausea/vomiting and pneumonitis. Conclusions: N+I did not meet prespecified criteria to declare a signal of activity in pts with OC and BRCA1/2 mut. However, given 22% of pts had PR (2 with >1 year duration) in this heavily pretreated cohort, additional study may be warranted to further evaluate efficacy. Clinical trial information: NCT02693535 . [Table: see text]

Temsirolimus (T) in patients (pts) with solid tumors with PIK3CA mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

3117 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in cohorts of pts with breast cancer (BC) and other solid tumors with PIK3CA mut treated with T are reported. Methods: Eligible pts had BC or other solid tumors, measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. After antihistamine pre-tx, 25 mg of T was infused over 30-60 minutes once weekly until disease progression. Primary endpoint was disease control (DC), defined as complete or partial (PR) response, or stable disease of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. For the BC cohort, Simon’s optimal 2-stage design with null DC rate of 15% vs. 35% (power=0.85, α=0.10) was used with stage 1 (n=10) stopping for futility if < 2/10 pts had DC. Low accruing histology-specific cohorts with PIK3CA and T tx were collapsed into 1 histology-pooled (HP) cohort. For the HP cohort, the hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test with α=0.10. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: 12 pts with PIK3CA mut with BC and 29 pts with PIK3CA mut in other solid tumors (across 9 tumor types) were enrolled. 2 pts (1 in each cohort) were found to be ineligible after enrolling and were not included in efficacy analyses. Demographics and outcomes for each cohort are shown. At the end of stage 1 in the BC cohort, 1 PR was observed for DC and OR rates of 9%; the cohort was closed for futility (p=0.83). For the HP cohort, 3 PR and 5 SD16+ were observed for DC rate of 29% (p=0.049) and OR rate of 11%; the null hypothesis was rejected. Cancer types in pts with OR or SD16+ included cervical, ovarian and head/neck; most common muts were H1047R/L (3), E545K (2) and E542K (2). 1 pt with ovarian and H1047R has ongoing PR at 86 wks. 11/41 pts had ≥1 tx-related grade 3-4 adverse or serious adverse event, including anemia, headache, hyperglycemia, hypertension, hypertriglyceridemia, mucositis oral, lymphocyte, neutrophil or platelet count decrease, pneumonitis, and sepsis. Conclusions: Although T does not appear to have antitumor activity in pts with BC with PIK3CA mut, it does show antitumor activity in pts with other solid tumors with PIK3CA mut and warrants further study. Clinical trial information: NCT02693535 . [Table: see text]

Abstract CT226: Crizotinib (C) in patients (pts) with solid tumors with MET amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Abstract Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors and MET amp or mut treated with C are reported. Methods: Eligible pts had no standard treatment (tx) options, had measurable disease, ECOG performance status (PS) 0-2, and adequate organ function. Pts with non-small cell lung cancer were excluded. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received C at 250 mg orally BID until disease progression. Low accruing histology-specific cohorts with MET amp or mut were collapsed into 1 histology-pooled cohort for analysis. Primary end point was disease control (DC) per investigator, defined as complete or partial response (PR) or stable disease (SD) of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. The primary end point was summarized as a proportion and the hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test with α= 0.10. Other end points were progression-free survival (PFS), overall survival (OS), duration of response and SD, and safety. Results: 31 pts with solid tumors (12 tumor types) and MET mut only (n=10), amp only (n=19), or mut and amp (n=1) were enrolled; 1 pt with overexpression was ineligible. 3 additional pts were unevaluable for efficacy. Table shows demographics and outcomes. 2 PR (both esophageal adenocarcinoma with MET amp) and 4 SD16+ (2 renal cell carcinoma, 1 with mut, 1 with amp; colorectal with amp; small intestine with amp) were observed for DC rate of 21% (1-sided 90% CI: 12%, 100%) and objective response rate of 7% (95% CI: 1%, 24%). The null DC rate was not rejected. 5 pts had ≥1 grade 3 tx-related adverse or serious adverse event. Conclusions: C did not meet prespecified criteria to declare a signal of activity in pts with solid tumors with MET amp or mut. Table: Baseline Characteristics (N=31); Efficacy Outcomes (n=28); Toxicity Outcomes (N=31) Median (Med) age, years (range) 61 (30, 82) Female, % 16 (52) ECOG PS, % 0 15 (48) 1 12 (39) 2 4 (13) Prior systemic regimens, % 1 3 (10) 2 5 (16) ≥3 23 (74) DC rate, % (OR and SD16+) (1-sided 90% CI) 21 (12, 100) Objective response rate, % (95% CI) 7 (1, 24) Med PFS, wks (95% CI) 8 (8, 13) Med OS, wks (95% CI) 37 (26, 68) Duration of response, wks (n=2) 14 and 20 Med duration SD, wks (n=4) 27 (26, 28) Number of pts1 with tx-related grade 3 adverse or any grade serious adverse event AE2 5 (16) SAE3 3 (10) 1Pts may have experienced one or more events 2ALT increase, diarrhea and all SAEs 3Acute kidney injury, ALT increase, AST increase, blood bilirubin increase, creatinine increase, dehydration, fatigue, GGT increase, hyperkalemia, nausea, sinus bradycardia Citation Format: Kathryn F. Mileham, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Herbert L. Duvivier, Carmen J. Calfa, Carrie L. Dul, Alissa S. Marr, Eugene R. Ahn, Deepti Behl, Michael J. Hall, Inderjit Mehmi, Anu Gaba, Rom Leidner, Mark M. Zalupski, Gina N. Grantham, Abigail Gregory, Susan Halabi, Richard L. Schilsky. Crizotinib (C) in patients (pts) with solid tumors with MET amplification (amp) or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT226.

Abstract CT231: Temsirolimus (T) in patients (pts) with solid tumors with PTEN mutation (mut): results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Abstract Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with PTEN mut treated with T are reported. Methods: Eligible pts had no standard treatment (tx) options, measurable disease, ECOG performance status (PS) 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. After antihistamine pre-tx, 25 mg T was infused over 30-60 minutes once weekly until disease progression. Low accruing histology-specific cohorts with PTEN mut were collapsed into 1 histology-pooled cohort for analysis. Primary end point was disease control (DC), defined as complete or partial response (PR) or stable disease (SD) of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. The primary end point was summarized as a proportion and the hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test with alpha 0.10. Other end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), duration of SD and safety. DOR is defined as time from pt’s first documented objective response (OR) until progressive disease (PD). Duration of SD is defined as time from tx start to PD. Results: 34 pts with solid tumors (10 tumor types; 20/34 pts had prostate, soft tissue sarcoma [STS] or lung) with PTEN mut were enrolled. 6 pts were unevaluable for efficacy, 1 was ineligible. Table shows demographics, outcomes and toxicity. 2 pts obtained PR (prostate and STS) and 5 had SD16+ (lung, head and neck, breast, uterine, and site unspecified) for DC rate of 26% (1-sided 90% CI: 15.1%, 100%) and OR rate of 7% (95% CI: 1%, 24%). The null DC rate was rejected. Median PFS was 10 wks and median OS was 32 wks. Conclusions: T met prespecified criteria to declare a signal of activity in pts with solid tumors with PTEN mut. Table: Baseline Characteristics (N=34); Efficacy Outcomes (n=27); Toxicity Outcomes (N=34) Median (Med) age, years (range) 65 (42, 84) Female, % 14 (41) ECOG PS, % 0 13 (38) 1 18 (53) 2 3 (9) Prior systemic regimens, % 1 3 (9) 2 5 (15) ≥3 26 (77) DC rate, % (OR and SD16+) (1-sided 90% CI) 26 (15.1, 100) OR rate, % (95% CI) 7 (1, 24) Med PFS, wks (95% CI) 10 (7, 17) Med OS, wks (95% CI) 32 (13, 42) DOR, wks (n=2) 11 and 55 Med duration SD, wks (n=5) 27 (24, 36) Number of pts1 with tx-related grade 3-4 AE or SAE AE2 12 (35) SAE3 6 (18) 1Pts may have experienced one or more events 2alkaline phosphatase increase, anemia, chronic kidney disease, diarrhea, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, lung infection, oral pain and all SAEs 3acute kidney injury, dyspnea, generalized muscle weakness, hypophosphatemia, lung infection, oral mucositis, pericardial effusion Citation Format: Kristopher Wentzel, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Li Ding, Evan Pisick, Mridula Krishnan, Deepti Behl, Olatunji B. Alese, Carmen J. Calfa, Kathrine A. Cooper, Herbert L. Duvivier, Raghava Reddy Induru, Janet C. Ruzich, Song Zhao, Gina N. Grantham, Abigail Gregory, Susan Halabi, Richard L. Schilsky. Temsirolimus (T) in patients (pts) with solid tumors with PTEN mutation (mut): results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT231.

Pertuzumab plus trastuzumab (P+T) in patients (pts) with biliary tract cancer (BTC) with ERBB2/3 amplification (amp), overexpression (oe), or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

546 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pts with BTC with ERBB2/3 amp, oe, or mut treated with P+T are reported. Methods: Eligible pts had advanced BTC, no standard treatment (tx) options, measurable disease, ECOG Performance Status (PS) 0-2, and adequate organ function. Genomic testing was done in CLIA-certified, CAP-accredited labs. Dosing of P was 840 mg IV over 60 minutes (m), then 420 mg IV over 30-60 m Q3 weeks (wks); T was 8 mg/kg IV over 90 m, then 6 mg/kg IV over 30-60 m Q3 wks until disease progression. Primary end point was disease control (DC), defined as complete (CR) or partial (PR) response per RECIST v. 1.1, or stable disease (SD) at 16+ wks (SD16+). Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 has DC, 18 more pts are enrolled; otherwise, cohort is closed for futility. If ≥7 of 28 pts has DC, the null DC rate is rejected. Secondary end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), duration of SD and safety. DOR is defined as time from pt’s first documented objective response (OR) to progressive disease (PD). Duration of SD is defined as time from start of tx to PD. Results: 29 pts with BTC (15 gallbladder (GB), 11 biliary duct (BD), 3 ampulla of Vater) and ERBB2/3 amp, oe, or mut were enrolled from Feb 2017 to Jan 2022. Median (med) age was 66 years (yrs) (range, 34-83 yrs). 66% of pts were female; 52% were White, 21% were Black/African American, 10% were Asian/Asian American; 83% were not Hispanic or Latino. 83% of pts had ECOG PS 0-1 and 48% had ≥3 prior systemic regimens. 1 pt was not evaluable and excluded from efficacy analysis. The table shows efficacy outcomes. 1 pt had CR (GB; ERBB2 amp; DOR: 71.1 wks), 8 pts had PR (6 GB/2 BD; 5 ERBB2 amp; 2 ERBB2 mut; 1 ERBB3 mut/ ERBB2 amp; med DOR: 30.4 wks (4.4 to 68.9 wks)) and 2 pts had SD16+. 4 pts with a KRAS mut did not achieve OR or SD16+. 4 pts had a Grade 3 drug-related adverse or serious adverse event (SAE): anemia, diarrhea, infusion related reaction (SAE), and fatigue. Conclusions: P+T demonstrated antitumor activity in pts with advanced BTC with ERBB2/3 alterations. These data, along with results previously reported by other studies, support continued study of P+T in pts with ERBB2 amplified BTC tumors. Clinical trial information: NCT02693535 . [Table: see text]

Olaparib (O) in patients (pts) with colorectal cancer (CRC) with ATM mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

122 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of pts with CRC with ATM mut treated with O are reported. Methods: Eligible pts had advanced CRC with ATM mut, no standard treatment (tx) options, measurable disease, ECOG Performance Status (PS) 0-2, and adequate organ function. Genomic testing was done in CLIA-certified, CAP-accredited labs. Recommended dosing for O was 300 mg twice daily (tablets) or 400 mg twice daily (capsules) until disease progression. Primary end point was disease control (DC), defined as complete or partial (PR) response per RECIST v. 1.1, or stable disease (SD) at 16+ weeks (wks) (SD16+). Simon 2-stage design tested the null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 has DC, 18 more pts are enrolled; otherwise, cohort is closed for futility. If ≥7 of 28 pts has DC, the null DC rate is rejected. Secondary end points were progression-free survival (PFS), overall survival (OS), duration of response (DOR), duration of SD, and safety. DOR is defined as time from the pt’s first documented objective response (OR) until progressive disease (PD). Duration of SD is defined as time from start of tx to PD. Results: 30 pts with CRC and ATM mut were enrolled from Sept 2016 to Aug 2019. 3 pts were not included in efficacy outcomes: 2 pts had no post-baseline tumor evaluation; 1 pt was found to be ineligible after receiving 1 dose. 1 PR ( ATM P938fs*11 and RAD50 variant of unknown significance (VUS); DOR was 18.6 wks) and 3 SD16+ ( ATM R1875*, splice site 4237-11_4241del16, E522*; duration of SD was 19.7, 25.3 and 27.0 wks, respectively) were observed for DC rate of 23% (95% CI, 6% to 39%) and OR rate of 4% (95% CI, 0.1% to 19%). The null DC rate was not rejected (p=0.38). 6/30 pts had a BRCA2 co-alteration, but none of these pts achieved OR or SD16+; no pts had a BRCA1 co-alteration; aside from the pt with PR and RAD50 VUS, only 1 other pt who achieved OR or SD16+ had a co-alteration among the other homologous recombination-related genes examined ( ATR VUS). 7 pts had ≥1 Grade 3 adverse or serious adverse event (SAE) at least possibly related to O, including urinary tract infection, white blood cell decreased, febrile neutropenia (SAE), anemia (1 SAE), lung infection (SAE), fatigue (SAE), and nausea (SAE). Conclusions: Monotherapy O does not show sufficient antitumor activity in pts with advanced CRC with ATM mut to warrant further study. Clinical trial information: NCT02693535 . [Table: see text]

Cobimetinib Plus Vemurafenib in Patients With Colorectal Cancer With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. The results of a cohort of patients with colorectal cancer (CRC) with BRAF mutations treated with cobimetinib (C) plus vemurafenib (V) are reported. Eligible patients had advanced CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with BRAF V600E/D/K/R mutations, and no MAP2K1/2, MEK1/2, or NRAS mutations. C was taken 60 mg orally once daily for 21 days followed by seven days off, and V was taken 960 mg orally twice daily. Simon's two-stage design was used with a primary study end point of objective response or stable disease of at least 16 weeks duration. Secondary end points were progression-free survival, overall survival, and safety. Thirty patients were enrolled from August 2016 to August 2018; all had CRC with a BRAF V600E mutation except one patient with a BRAF K601E mutation. Three patients were not evaluable for efficacy. Eight patients with partial responses and six patients with stable disease of at least 16 weeks duration were observed for disease control and objective response rates of 52% (95% CI, 35 to 65) and 30% (95% CI, 14 to 50), respectively. The null hypothesis of 15% disease control rate was rejected (P < .0001). Thirteen patients had at least one grade 3 adverse event or serious adverse event at least possibly related to C + V: anemia, decreased lymphocytes, dyspnea, diarrhea, elevated liver enzymes, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, and upper gastrointestinal hemorrhage. The combination of C + V has antitumor activity in heavily pretreated patients with CRC with BRAF mutations.

98P Olaparib (O) in patients (pts) with solid tumors with BRCA1/2 mutation (mut): Results from the targeted agent and profiling utilization registry (TAPUR) study

TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with BRCA1/2 mut treated with O are reported.

978P Pertuzumab plus trastuzumab (P+T) in patients (pts) with lung cancer (LC) with ERBB2 mutation (mut) or amplification (amp): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study

TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers and specific genomic alterations. Results in a cohort of pts with LC and ERBB2 mut or amp treated with P+T are reported.