Abstract 436P
Background
Adenosine A2a receptor (A2AR) blockade in combination with anti-programmed death-1 (PD-1) antibody (Ab) may alleviate immune-suppression, reduce tumor growth, and increase antitumor activity of anti-PD-1 Ab. Taminadenant (A2AR antagonist) +/- spartalizumab (anti-PD-1 Ab) has preliminary antitumor activity in a Ph Ib study in non-small cell lung carcinoma. We present results of taminadenant + spartalizumab in a Ph II study in MSS CRC (NCT03207867).
Methods
In Part I of the study, pts with MSS CRC were treated with 160 mg oral taminadenant twice daily continuously + 400 mg intravenous spartalizumab every 4 weeks. The primary objective was to evaluate efficacy, using overall response rate (ORR by RECIST v1.1). Disease control rate (DCR) is the proportion of complete response, partial response (PR), or stable disease (SD). Following an interim analysis after the initial 14 evaluable pts with MSS CRC, 40 additional pts were enrolled in two groups: RAS-wildtype (WT) and RAS-mutant (Mt). Tumor biopsies were taken pre- and on-treatment.
Results
As of 20 Nov 2020, 58 pts with MSS CRC were enrolled (RAS-WT: n=27; RAS-Mt: n=29; RAS-Unknown [Uk]: n=2); demographics were similar across cohorts. The majority (69%) of pts had received ≥3 lines of prior therapy. Of 58 pts, 1 (2%) had a PR (Mt: n=1), 11 (19%) SD (WT: n=7; Mt: n=4), 34 (59%) progressive disease (WT: n=16; Mt: n=16; Uk: n=2), and 12 (21%) response unknown (WT: n=4; Mt: n=8). Of the pts with SD, 5 showed tumor shrinkage (WT: n=4; Mt: n=1); 4 had response for >6 months and 1 discontinued treatment due to an adverse event (AE). ORR was 2% (95% CI: 0.0–9.2), and DCR was 21% (95% CI: 11.2–33.4). Of 58 pts, common all-grade (G) treatment-related AEs ([TRAEs]; ≥15% pts) were fatigue (21%) and decreased appetite (16%); ≥G3 TRAEs (≥5% pts) were aspartate/alanine aminotransferase (5/9%) or lipase (5%) increase. Pharmacokinetics and biomarker data will be presented.
Conclusions
Efficacy results of taminadenant + spartalizumab showed 5 pts obtained clinical benefit (1 PR and 4 sustained SD with tumor shrinkage), with no difference in response between RAS-WT and RAS-Mt. Taminadenant + spartalizumab was well tolerated in pts with MSS CRC.
Clinical trial identification
NCT03207867: Protocol number: CNIR178X2201; release date: October 22, 2020.
Editorial acknowledgement
Writing and editorial assistance was provided by Heather Latimer of ArticulateScience, UK.
Legal entity responsible for the study
Novartis Pharmaceutical Corporation.
Funding
Novartis Pharmaceutical Corporation.
Disclosure
O. Saavedra Santa Gadea: Financial Interests, Personal, Other, Travel, accommodations, expenses: MSD, Kyowa Kirin. R. Greil: Financial Interests, Personal, Advisory Role, Honoraria, research funding, travel and expenses: Celegne, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, Janssen. M.J.A. de Jonge: Financial Interests, Personal, Advisory Board: Faron Pharmaceuticals Ltf. D. Tan: Financial Interests, Personal, Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer; Financial Interests, Personal, Other, Travel, Accomodation, Expenses: Pfizer, Boehringer Ingelheim, Roche; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb, Takeda, Novartis, Roche, Pfizer; Financial Interests, Institutional, Funding, Research Funding: Novartis, GlaxoSmithKline, AstraZeneca. G. Jerusalem: Financial Interests, Personal, Other, outside the submitted work: Novartis; Roche; Pfizer; Lilly; Amgen; BMS; AstraZeneca; Daiichi Sankyo; AbbVie; Financial Interests, Institutional, Research Grant, outside the submitted work: Roche; Novartis; Pfizer; Non-Financial Interests, Other, outside the submitted work: Novartis; Roche; Pfizer; Lilly; Amgen; BMS; AstraZeneca; Medimmune; MerckKGaA. P. Grell: Financial Interests, Personal, Advisory Role, Consulting fees: Roche, Servier; Financial Interests, Personal, Other, Travel, Accomodation, Expenses: Roche, Servier; Financial Interests, Institutional, Funding, Research Funding: Novartis. Z. Wainberg: Other, Personal, Other, Honoraria: Amgen; AstraZeneca; Daiichi; Bayer; BMS; Merck; Ipsen; Five Prime; Gilead; Arcus; Astellas; Molecular Templates; Array; Other, Advisory Role: Amgen; AstraZeneca; Daiichi; Bayer; BMS; Merck; Ipsen; Five Prime; Gilead; Arcus; Astellas; Molecular Templates; Array; Financial Interests, Institutional, Research Grant: Amgen; AstraZeneca; Daiichi; Bayer; BMS; Merck; Ipsen; Five Prime; Gilead; Arcus; Astellas; Molecular Templates; Roche/Genentech; Array/Pfizer. J. Wolf: Financial Interests, Personal, Advisory Board, Advisory Board and Lecture Fees: Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer-Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Institutional, Funding: BMS, Janssen Pharmaceutica, Novartis, Pfizer. M.S. Carlino: Financial Interests, Personal, Advisory Role: Amgen; BMS; Eisai; Ideaya; MSD; Nektar; Novartis; Oncosec; Pierre-Fabre; Qbiotics; Regeneron; Roche; Sanofi; Financial Interests, Personal, Other, Honoraria: MSD; BMS; Novartis. S. Kasper: Other, Personal, For conducting studies: Novartis; Other, Personal, For conducting clinical trials: BMS; Roche; Financial Interests, Personal and Institutional, Research Grant, For conducting clinical trials: BMS; Roche; Financial Interests, Personal, Other: Amgen; Sanofi Aventis; Financial Interests, Personal and Institutional, Research Grant, For ISTs: Lilly; Merck Serono; Servier. T.A. Yap: Financial Interests, Institutional, Research Grant: Artios, AstraZeneca, Bayer, Clovis, Constellation, Cyteir, Eli Lilly, EMD Serono, Forbius, F-Star, GlaxoSmithKline, Genentech, ImmuneSensor, Ipsen, Jounce, Karyopharm, Kyowa, Merck, Novartis, Pfizer, Ribon Therapeutics, Regeneron, Repare, Sanofi, Scholar. J. Otero: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares, Employee of Novartis: Novartis. X. Yang: Financial Interests, Personal, Full or part-time Employment, Employee of Novartis: Novartis. V. Nesbitt: Financial Interests, Personal, Full or part-time Employment, Employee of Novartis: Novartis; Financial Interests, Personal, Stocks/Shares, RSUs: Novartis. J. Kim: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. L. Ho Lee: Financial Interests, Personal, Full or part-time Employment: Novartis. S. Choudhury: Financial Interests, Personal, Full or part-time Employment, Employee of Novartis: Novartis. T.A. Leal: Financial Interests, Personal, Advisory Board: Takeda, Blueprint, Janssen; Financial Interests, Personal, Advisory Board: BMS, Jazz Pharmaceuticals, EMD Serono; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BeyondSpring, InvisionFirst; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Bayer, Merck; Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Board: Novocure, Daiichi Sankyo, Lilly. All other authors have declared no conflicts of interest.