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

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 from 2 cohorts of pts with solid tumors with CDK4 or CDK6 amp 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 labs. Amp cut-offs were defined per NGS providers. Recommended dosing was 125 mg P orally once daily for 21 days on followed by 7 days off, until disease progression. Low accruing histology-specific cohorts with CDK4 or CDK6 amp were collapsed into 2 histology-pooled cohorts for analysis. Primary endpoint was disease control (DC) defined as investigator assessment of complete 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 evaluated by a 1-sided exact binomial test (α= 0.10; power 65% and 58%, respectively). Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response (OR), duration of response (DOR) and SD, and safety.

Results

Pts with solid tumors with CDK4 amp (N=16) or CDK6 amp (N=15) were enrolled. 1 pt from each cohort was not evaluable for efficacy. Table shows demographics and outcomes. For the CDK4 cohort, 2 pts had SD16+ for a DC rate of 13% (p=0.72); the null DC rate was not rejected. Of pts with SD16+, duration of SD was 28 (ovarian) and 52 (adrenal) wks. For the CDK6 cohort, 1 pt had a PR (pancreatic, DOR = 8 wks) for a DC rate of 7% (p=0.897) and OR rate of 7%; the null DC rate was not rejected. 6/31 pts had ≥1 tx-related grade 3-4 adverse or serious adverse event of neutropenia or thrombocytopenia.

Conclusions

P did not show antitumor activity in heavily pretreated pts with advanced solid tumors with CDK4 or CDK6 amp. Table: 207P

Demographics and efficacy outcomes

Clinical trial identification

NCT02693535 Study launched 14 March, 2016.

Editorial acknowledgement

The authors thank the patients who participated, the clinical centers and staff, and the TAPUR Study team.

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, Seagen and Taiho Oncology.

Disclosure

M. Rothe: Financial Interests, Institutional, Full or part-time Employment, I work as the Senior Biostatistician on the TAPUR Study at ASCO.: American Society of Clinical Oncology. 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. K.F. Mileham: Financial Interests, Personal, Advisory Board: Regeneron, AstraZeneca, Mirati, Takeda, Genentech; Financial Interests, Personal, Invited Speaker: ACCC, Chest, OncLive, Merck. H.L. Duvivier: Financial Interests, Personal, Invited Speaker, Speakers Bureau: Guardant Health; Non-Financial Interests, Member: ASCO. M. Akce: Financial Interests, Personal, Advisory Board: Eisai, Ipsen, GSK, QED Therapeutics, Exelixis, AstraZeneca, Curio Science, Genentech, Isofol, Taiho, Incyte; Financial Interests, Institutional, Local PI: Tesaro, RedHill Biopharma, Polaris, Bristol Myers Squibb-Ono Pharmaceutical, Xencor, Merck Sharp & Dohme, Eisai, Pfizer, Bellicum Pharmaceuticals, Boehringer Ingelheim, Syros Pharmaceuticals, IMPAC Medical Systems, AstraZeneca; Financial Interests, Institutional, Trial Chair: Bayer; Financial Interests, Personal and Institutional, Steering Committee Member: AstraZeneca. D. behl: Financial Interests, Personal, Advisory Board, Member of invited advisory board on Adaura, Caspian and Poseidon trials: AstraZeneca; Financial Interests, Personal, Invited Speaker, Speaker for Tagrisso and Durva: AstraZeneca; Financial Interests, Personal, Advisory Board, Invited advisor discussion on IO: Lilly; Financial Interests, Personal, Advisory Board, Lonsurf: Taiho; Financial Interests, Personal, Invited Speaker, Panel discussion: Guardant; Financial Interests, Personal, Advisory Board, ad board member: Amgen; Financial Interests, Personal, Advisory Board, Amivantamab ad board: Janssen; Financial Interests, Personal, Advisory Board: BMS; Non-Financial Interests, Member of Board of Directors, Not a paid position: SCOPe ( phase 1 partnership with UCD). N. Vijayvergia: Financial Interests, Personal, Financially compensated role, Participated in a few market research interviews - blinded and no connection to any health care firm: Guidepoint Global; Financial Interests, Personal and Institutional, Advisory Role, Participated in Ad board: Novartis; Financial Interests, Personal and Institutional, Advisory Board, Participated in Ad board: AstraZeneca/Daiichi Sankyo ; Financial Interests, Personal and Institutional, Advisory Board, Peer review through NCCN: Taiho Oncology ; Financial Interests, Personal and Institutional, Advisory Board, Participated in pharma sponsored Case discussion session: Tersera therapeutics ; Financial Interests, Personal and Institutional, Advisory Board, Ad board participation: Ipsen ; Financial Interests, Personal and Institutional, Advisory Board: ITM Isotope Technologies Munich ; Non-Financial Interests, Personal and Institutional, Advisory Board, DSMB member: RayzeBio ; Financial Interests, Personal and Institutional, Research Funding, research funding: Zymeworks , Bristol Myers Squibb/Medarex ; Financial Interests, Personal and Institutional, Research Funding, NCCN sponsored grant for clinical trial with Neratinib: Puma Biotechnology ; Financial Interests, Personal and Institutional, Research Funding, Research funding: Oryzon Genomics . A. Gaba: Financial Interests, Institutional, Local PI, Clincial trial. Payment to my institution: GSK; Non-Financial Interests, Member, Advocacy: Association of Clinical Oncology. F. Meric-Bernstam: Financial Interests, Personal, Other, Consultant: AstraZeneca, F. Hoffman-La Roche Ltd., Zymeworks, OnCusp Therapeutics; Financial Interests, Personal, Advisory Board, Advisory Board/Consultant: Seagen; Financial Interests, Personal, Advisory Board: Zentalis, Karyopharm, Biovica, Eisai, Protai, TheraTechnologies; Financial Interests, Personal, Other, Consulting: Tallac Therapeutics, Lengo Therapeutics, LOXO-Oncology, Black Diamond, Infinity Pharmaceuticals, AbbVie, GT Aperion, Ecor1; Financial Interests, Personal, Other, Consutling: Menarini Group; 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, Local PI: Calithera Biosciences, Curis Inc., Debiopharm International, Guardant Health Inc., Klus Pharma, Novartis; Financial Interests, Institutional, Other, Local PI / Steering Committee Member: Genentech Inc.; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical Co., Puma Biotechnology Inc., Repare; Other, Travel Support: Cholangiocarcinoma Foundation; Other, Travel support: European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO). S.M. Schuetze: Financial Interests, Personal, Other, DSMC member: BioAtla; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Local PI: Tracon, Adaptimmune, Boehringer Ingelheim, Shanghai Pharmaceuticals, Rain Therapeutics. A. Gregory: Financial Interests, Institutional, Full or part-time Employment: American Society of Clinical Oncology; Other, Family member works for Pfizer: Pfizer. S. Halabi: Financial Interests, Personal, Other, Member of DSMB: Sanofi, Aveo Oncology, BMS, Janssen; 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, Advisory Board, Clinical advisory board: Syapse; Financial Interests, Personal, Advisory Board, Scientific advisory board: ZephyrAI; Financial Interests, Personal, Member of Board of Directors: Leap Therapeutics; Financial Interests, Personal, Stocks/Shares, Stock options: Cellworks, Clarified Precision Medicine, Bryologyx; Financial Interests, Personal, Stocks/Shares, Stock: EQRx; Financial Interests, Personal, Stocks/Shares, Stock ownership/Member, Board of Directors: Leap Therapeutics; Financial Interests, Institutional, Coordinating PI, Research grant to ASCO to support TAPUR clinical trial: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Genentech, Lilly, Merck, Pfizer, Seagen; Financial Interests, Institutional, Coordinating PI, Research grant to ASCO to support TAPUR trial: Taiho; Non-Financial Interests, Leadership Role, Chairman: WIN Consortium; Non-Financial Interests, Member of Board of Directors, Board member: Alliance Clinical Trials Group, Friends of Cancer Research, Reagan Udall Foundation for FDA, EORTC; Non-Financial Interests, Advisory Role, Member, Strategic Executive Advisory Committee: Canadian Cancer Trials Group; Non-Financial Interests, Advisory Role, Chair, Scientific Advisory Board: Ontario Institute for Cancer Research. All other authors have declared no conflicts of interest.