Abstract 98P
Background
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.
Methods
Eligible pts had solid tumors, 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 labs. Recommended dosing was O orally twice daily for total daily dose of 600 mg (tablets) or 800 mg (capsules) until disease progression. Low accruing histology (Hs)-specific cohorts with the same genomic alteration were collapsed into a Hs-pooled cohort for this analysis. Primary endpoint was disease control (DC) defined as complete (CR) or partial (PR) response or stable disease at 16+ wks (SD16+) per RECIST v1.1. For Hs-pooled cohorts with sample size >28, if the lower limit of a 1-sided 90% CI is >15%, the null hypothesis of DC rate of 15% is rejected. 2-sided 95% CIs were used for other efficacy endpoint estimates. Secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety.
Results
32 pts with solid tumors with BRCA1 (N=13) or BRCA2 (N=19) mut were enrolled from July 2016 to December 2018. All pts were evaluable for efficacy and toxicity. The table shows demographics and outcomes. 2 CR (1 BRCA1, stomach cancer; 1 BRCA2, unknown primary), 6 PR (2 BRCA1; 4 BRCA2; all had unique primary tumors) and 5 SD16+ (1 BRCA1; 4 BRCA2; 2/5 pts colorectal cancer, 3/5 had unique primary tumors) were observed for DC rate of 41% (90% CI, 29% to 100%) and OR rate of 25% (95% CI, 11% to 43%). The null DC rate was rejected. 12 pts had ≥1 Grade 3/4 adverse or serious adverse event at least possibly related to O.
Conclusions
O monotherapy demonstrated evidence of anti-tumor activity in pts with various solid tumors with BRCA1/2 mut. Table: 98P
Baseline characteristics and efficacy outcomes (N=32)
| Median (Med) age, years (range) | 65 (34-89) | |
| Female, % | 9 (28) | |
| ECOG PS, %1 | 0 | 13 (41) |
| 1 | 12 (38) | |
| 2 | 7 (22) | |
| Prior systemic regimens, % | 1 | 10 (31) |
| 2 | 6 (19) | |
| ≥3 | 16 (50) | |
| DC rate, % (OR, SD16+) (1-sided 90%CI) | 41 (29, 100) | |
| OR rate, % (95% CI) | 25 (11, 43) | |
| Med PFS, wks (95% CI) | 15.7 (8.3, 27.3) | |
| Med OS, wks (95% CI) | 45.0 (17.7, 81.4) | |
| Duration of CR, wks (N=2) | 24.3 and 84.1 | |
| Med duration PR (range), wks (N=6) | 16.0 (8.1, 24.7) |
1Percentages total greater than 100% due to rounding
Clinical trial identification
NCT02693535 Study launched on 14 March, 2016.
Editorial acknowledgement
The authors thank the patients who participated as well as the clinical center and staff, and Abby Gregory, ASCO, for manuscript preparation assistance.
Legal entity responsible for the study
American Society of Clinical Oncology, Inc. (ASCO).
Funding
AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Genentech, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer and Seagen.
Disclosure
E. Ahn: Financial Interests, Personal, Full or part-time Employment, I work for CTCA Chicago which is a for-profit institution but will become not for profit within the next year. I am including this in case that counts as a potential conflict of interest: Cancer Treatment Centers of America; Financial Interests, Personal, Invited Speaker, I serve as Deputy Medical Director of Research and I am compensated with a set salary for my efforts working for CTCA-Chicago which currently is for-profit. However I do not make any additional salary based on research metrics: Cancer Treatment Centers of America. M. Rothe: Financial Interests, Institutional, Full or part-time Employment: ASCO. P.K. Mangat: Financial Interests, Institutional, Full or part-time Employment: American Society of Clinical Oncology. E. Garrett-Mayer: Financial Interests, Institutional, Full or part-time Employment: American Society of Clinical Oncology; Financial Interests, Personal, Royalties, Book: Principles of Anticancer Drug Development: Humana Press. T. Al Baghdadi: Financial Interests, Personal, Advisory Board: Cardinal health, Amgen, Bristol Myer Squibb; Financial Interests, Personal, Other, ABIM oncology board member: ABIM; Financial Interests, Personal, Stocks/Shares: BMY, EPZM, HRTX; Financial Interests, Personal, Stocks/Shares, Sold less than 2 years ago: AZN. A.D. Baron: Financial Interests, Personal, Invited Speaker, Speaker's Bureau: Bristol Myers Squib, Eli Lilly, Bayer, Janssen. J.C. Krauss: Financial Interests, Institutional, Invited Speaker, Site PI for clinical trial: Sumitomo Dainippon Pharma Oncology, Inc., Novartis Pharmaceuticals Corporation, Amgen, Inc., Merck Sharp & Dohme Res. Labs TO Nsabp Foundation; Financial Interests, Institutional, Invited Speaker, Site PI for clinical Trial: Hutchison MediPharma Limited TO Syneos Health, LLC, Ignyta, Inc. TO Quintiles, Inc.; Financial Interests, Institutional, Invited Speaker, Site PI for Clinical Trial: Isofol Medical AB; Financial Interests, Institutional, Invited Speaker, Site PI for a clinical trial: AbbVie, Inc., Bristol Myers Squibb, MedImmune, Pfizer, Daiichi Sankyo Company, Ltd. TO Syneos Health, LLC. A.S. Balmanoukian: Financial Interests, Personal, Other, on the Speakers Bureau: BMS, Genentech, AstraZeneca; Financial Interests, Institutional, Other, Sub-investigator on the industry sponsored trial at our institution: BMS; Financial Interests, Institutional, Other, Sub-investigator on the industry sponsored trial at our site. No direct compensation: MedImmune; Financial Interests, Institutional, Other, Sub investigator on the industry sponsored trial at our site: Regeneron; Financial Interests, Institutional, Other, Both PI and Sub-I on Seattle Genetics trials at our site: Seattle Genetics; Financial Interests, Institutional, Other, sub-I on industry sponsored trial at our site: Pfizer; Financial Interests, Institutional, Other, sub-I on industry sponsored trial at out site: Nextcure; Financial Interests, Institutional, Other, Sub-I on industry sponsored trial at our site: Incyte, Rubius Therapeutics; Financial Interests, Institutional, Other, Sub-I on industry sponsored study at our site: TAIGA Therapeutics, Treadwell Therapeutics, Tyrnovo, Mereo Biopharma, Surface Therapeutics, Tmunity; Financial Interests, Institutional, Invited Speaker, Both PI and sub-I on GSK sponsored trials at our site: GSK; Financial Interests, Institutional, Other, sub-I on industry sponsored trials at our site: Epizyme; Financial Interests, Institutional, Invited Speaker, Both PI and sub-I on Arcus sponsored trials at our site: Arcus; Financial Interests, Institutional, Other, Sub-I on industry sponsored trials at our site: Amgen. J.R. Bauman: Financial Interests, Personal, Advisory Board: Kura, Janssen, Pfizer, Blueprint Medicine, Lilly, Merck, Mirati, Turning Point Therapeutics, Beigene. M.K. Hameed: Non-Financial Interests, Member: ASCO. K.F. Mileham: Financial Interests, Personal, Advisory Board: Regeneron, AstraZeneca, Mirati, BMS, G1Therapeutics; Financial Interests, Personal, Invited Speaker: ACCC, Chest, OncLive, Merck. F. Meric-Bernstam: Financial Interests, Personal, Other, Consultant: AstraZeneca, Debiopharm, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd., Tyra Biosciences, Xencor, Zymeworks, OnCusp Therapeutics; Financial Interests, Personal, Advisory Board, Advisory Board/Consultant: Seagen; Financial Interests, Personal, Advisory Board: Silverback Therapeutics, Zentalis, Karyopharm, Biovica, Eisai; Financial Interests, Personal, Other, Consulting: Tallac Therapeutics, Lengo Therapeutics, Loxo-Oncology, Black Diamond, Infinity Pharmaceuticals, AbbVie; Financial Interests, Institutional, Other, Local PI / Research Grant: Aileron Therapeutics, Bayer Healthcare, CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., eFFECTOR Therapeutics, Taiho Pharmaceutical Co.; Financial Interests, Institutional, Other, Local PI / Research Grant / Coordinating PI: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Calithera Biosciences, Curis Inc., Debiopharm International, Guardant Health Inc., Klus Pharma, Novartis, PPD Investigator Services; Financial Interests, Institutional, Other, Local PI / Steering Committee Member: Genentech Inc.; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical Co., Puma Biotechnology Inc., Repare. S.F. Powell: Financial Interests, Institutional, Invited Speaker: Alkermes, Merck, Bristol Myers Squibb, Pfizer, Actuate, Vyriad, Genentech, AstraZeneca, Incyte, Seattle Genetics, Sorrento; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb. E.S. Yang: Financial Interests, Personal, Advisory Board: Strata Oncology, Clovis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer; Financial Interests, Institutional, Research Grant: Eli Lilly, Puma; Financial Interests, Institutional, Invited Speaker: ASCO TAPUR; Non-Financial Interests, Member: AACR, ASCO, ASTRO, RSNA. R. O'Lone: Financial Interests, Institutional, Full or part-time Employment: ASCO. G.N. Grantham: Financial Interests, Institutional, Full or part-time Employment: ASCO. S. Halabi: Financial Interests, Personal, Other, Member of DSMB: Sanofi, Aveo Oncology; Financial Interests, Institutional, Funding: ASCO. R.L. Schilsky: Financial Interests, Personal, Advisory Board, Member, Clinical Advisory Board: Cellworks; Financial Interests, Personal, Advisory Board, Member, Mission Advisory Board: EQRx; Financial Interests, Personal, Advisory Board, Consultant: Illumina, Scandion Oncology, Clarified Precision Medicine, Bryologyx; Financial Interests, Personal, Stocks/Shares, Stock options: Cellworks, Clarified Precision Medicine, Bryologyx; Financial Interests, Personal, Stocks/Shares, Stock: EQRx; Financial Interests, Institutional, Invited Speaker, Research grant to ASCO to support TAPUR clinical trial: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Genentech, Lilly, Merck, Pfizer, Seagen; Non-Financial Interests, Leadership Role, Chairman: WIN Consortium; Non-Financial Interests, Invited Speaker, Board member: Friends of Cancer Research, Reagan Udall Foundation for FDA, EORTC, Alliance Clinical Trials Group; Non-Financial Interests, Advisory Role, Member, Strategic Executive Advisory Committee: Canadian Cancer Trials Group; Non-Financial Interests, Advisory Role, Co-chair, Scientific Advisory Board: Ontario Institute for Cancer Research. All other authors have declared no conflicts of interest.