Abstract 978P
Background
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.
Methods
Eligible pts had advanced LC of any histology, 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. Pts matched to P+T had LC with ERBB2 mut or amp. Recommended dosing was P at an initial dose of 840 mg intravenously (IV) over 60 minutes (m), then 420 mg IV over 30-60 m every 3 weeks (wks) and T at an initial dose of 8 mg/kg IV over 90 m, then 6 mg/kg IV over 30-60 m every 3 wks until disease progression. Primary endpoint was disease control (DC), defined as complete or partial (PR) response per RECIST v. 1.1, or stable disease at 16+ wks (SD16+). Simon 2-stage design tested 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 have DC, the null DC rate is rejected. Secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety.
Results
28 pts with LC (27 non-small cell, 1 small cell) and ERBB2 mut (N=15), ERBB2 amp (N=12), or both (N=1) were enrolled from November 2016 to July 2020. All pts were evaluable for efficacy and toxicity. The table shows demographics and outcomes. 3 PR (2 ERBB2 mut; 1 both mut and amp) and 7 SD16+ (5 ERBB2 mut; 2 amp) were observed for DC rate of 37% (95% CI, 21% to 50%) and OR rate of 11% (95% CI, 2% to 29%). The null DC rate was rejected (p=0.005). 5 pts had ≥1 Grade 3/4 adverse or serious adverse event at least possibly related to P+T. Table: 978P
Baseline characteristics and efficacy outcomes (N=28)
| Median (Med) age, years (range) | 64 (41-84) | |
| Female, % | 15 (54) | |
| ECOG PS, % | 0 | 9 (32) |
| 1 | 17 (61) | |
| 2 | 2 (7) | |
| Prior systemic regimens, % | 0 | 1 (4) |
| 1 | 9 (32) | |
| 2 | 5 (18) | |
| ≥3 | 13 (46) | |
| DC rate, % (OR or SD 16+) (95% CI) | 37 (21, 50) | |
| OR rate, % (95% CI) | 11 (2, 29) | |
| Med PFS, wks (95% CI) | 16.1 (8.6, 23.4) | |
| Med OS, wks (95% CI) | 54.4 (36.6, 101.4) | |
| Duration of PR, wks (N=3) | 13.1, 19.1, 56.3 |
Conclusions
Combination P+T showed evidence of anti-tumor activity in heavily pre-treated pts with LC and ERBB2 mut or amp.
Clinical trial identification
NCT02693535. Study launched on 14 March 2016.
Editorial acknowledgement
Abby Gregory, ASCO, for abstract preparation assistance.
Legal entity responsible for the study
American Society of Clinical Oncology, Inc. (ASCO).
Funding
Genentech, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Merck Sharp & Dohme Corp., a subsidiary of Merck &Co., Inc., Rahway, NJ, USA, Pfizer and Seagen.
Disclosure
A.K. Ganti: Financial Interests, Personal, Advisory Board, SCLC consultant: AstraZeneca; Financial Interests, Personal, Other, DSMC Chair: YMAbs Therapeutics; Financial Interests, Personal, Advisory Board: Cardinal Health, Mirati Therapeutics, BeiGene Therapeutics, Sanofi Genzyme; Financial Interests, Personal, Advisory Board, Scientific Advisor: Flagship Biosciences; Financial Interests, Personal, Invited Speaker, CME speaker: Plexus Communications; Financial Interests, Personal, Other, Associate Editor of JCO-OP: American Society of Clinical Oncology; Financial Interests, Personal, Other, DSMB member: Hoosier Cancer Research Network; Financial Interests, Personal, Royalties, Lung cancer Book Editor: Oxford University Press; Financial Interests, Institutional, Invited Speaker: Merck, TAB Biosciences, NEKTAR Therapeutics, Mirati Therapeutics; Non-Financial Interests, Other, Clinical Advisor on a current project: Jazz Pharmaceuticals; Non-Financial Interests, Institutional, Product Samples, Drug supply for a research project: Takeda Pharmaceuticals; Non-Financial Interests, Leadership Role, Board of Directors: Academic and Community Cancer Research United. 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. H. Duvivier: Financial Interests, Personal, Invited Speaker, Speakers Bureau: Guardant Health; Non-Financial Interests, Member: ASCO. 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. 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, Lutathera: AAA; 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, Invited Speaker, Amivantamab speaker: Janssen; Non-Financial Interests, Invited Speaker, Not a paid position: SCOPe (phase I partnership with UCD). H. Borghaei: Financial Interests, Personal, Advisory Board: BMS, Genentech, Eli-Lilly, Merck, EMD-Serono, AstraZeneca, Novartis, Genmab, Regeneron, Amgen, Takeda, PharmaMar, Jazz Pharma, Mirati, Daiichi, Guardant, Natera, Oncocyte, BeiGene, iTeo, Boehringer Ingelheim; Financial Interests, Personal, Other, Training discussion: Pfizer; Financial Interests, Personal, Other, DSMB: Novartis; Financial Interests, Institutional, Other, Clinical trial support: BMS, Amgen; Financial Interests, Personal, Stocks/Shares, Options for scientific advisory role: Sonnetbio; Financial Interests, Personal, Stocks/Shares, Options for scientific advisory board: Nucleai, Inspira (Rgenix); Financial Interests, Institutional, Invited Speaker, Investigator initiated trial support: BMS, Amgen, Lilly; Financial Interests, Personal and Institutional, Invited Speaker, Chair steering committee: Miratti; Financial Interests, Personal and Institutional, Invited Speaker: Amgen, AstraZeneca; Other, DSMB: Novartis, Takeda, Incyte. 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. A. Gaba: Financial Interests, Institutional, Invited Speaker, my institute gets paid for taking enrolling patients in the clinical trial: GSK. 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.