Abstract 709P
Background
NccRCC encompasses a heterogenous group of histologies comprising ∼25% of all RCC diagnoses with worse outcomes than ccRCC. Both C monotherapy and immune checkpoint inhibitors (ICIs) have shown preliminary activity in nccRCC, and several phase 2 trials are evaluating C in nccRCC. C promotes an immune-permissive environment which may enhance response to ICIs and has shown encouraging activity in combination with ICIs in tumor types including ccRCC, UC, mCRPC , and HCC. COSMIC-021, a multicenter phase 1b study, is evaluating the combination of C with A in various solid tumors (NCT03170960). We report initial results from cohort 10 in nccRCC.
Methods
Eligible patients (pts) had ECOG PS 0-1 and had received ≤1 prior VEGFR-TKI therapy for advanced nccRCC. Prior ICI or C therapy was not allowed. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. The primary endpoint is objective response rate (ORR) per RECIST v1.1 by investigator. Other endpoints include safety, duration of response (DOR), PFS, and OS.
Results
As of Mar 27, 2020, 30 pts were enrolled with a median follow-up of 9.2 mo (range 4, 16); histological subtypes were papillary, n=15; chromophobe, n=7; and other, n=8. Median age was 61 y, 87% were male, 70% had ECOG PS 0, 80% had prior nephrectomy, and 57% had ≥3 sites of disease. Five pts (17%) had received prior VEGFR-TKI therapy (two in combination with everolimus). 37% were favorable, 50% were intermediate, and 13% were poor risk by IMDC criteria. Grade 3/4 TRAEs occurred in 30%, with no grade 5 TRAEs. Hypophosphatemia was the most common grade 3/4 TRAE (4 [13%]). Confirmed ORR per RECIST v1.1 was 33%; ten pts had PRs (papillary, n=6; chromophobe, n=1; ccRCC, n=1; translocation, n=1; and unclassified, n=1). Responses occurred in all IMDC risk groups. DCR (CR+PR+SD) was 93%. Median DOR was 7.9 mo (range 1.0+, 8.3+). Increased median levels of activated peripheral cytotoxic T (+13%) and NK (+34%) cells were observed at day 21 with a concomitant decrease in immunosuppressive cells.
Conclusions
C + A demonstrated encouraging clinical activity in pts with nccRCC with an acceptable safety profile. Responses were observed in multiple histologies. Antitumor immunomodulatory effects were observed in peripheral blood with C + A.
Clinical trial identification
NCT03170960.
Editorial acknowledgement
Julie Lougheed, Exelixis.
Legal entity responsible for the study
Exelixis.
Funding
Exelixis.
Disclosure
B.A. McGregor: Honoraria (self), Advisory/Consultancy: Bayer, Astellas, AstraZeneca, Seattle Genetics, Exelixis, Nektar, Pfizer, Janssen, Genentech and EMD Serono; Research grant/Funding (institution): BMS, Exelixis, Genentech, Seattle Genetics, Calithera . N. Agarwal: Advisory/Consultancy: Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Janssen, Merck, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics.; Research grant/Funding (institution): AstraZeneca, Bavarian Nordic , Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Glaxo Smith Kline, Immunomedics, Janssen, Medivation, Merck, Nektar, New Link Genetics, Novartis, Pfizer, Prometh. C. Suarez: Advisory/Consultancy: Astellas, AstraZeneca, Bayer, BMS, Eusa, Ipsen, Novartis, Pfizer, Sanofi-Aventis, Roche, Merck Sharp & Dohme Corp; Speaker Bureau/Expert testimony: Bristol-Myers Squibb (Inst), Astellas, Ipsen, Pfizer; Travel/Accommodation/Expenses: Bristol-Myers Squibb (Inst), Pfizer, Roche. C-K. Tsao: Shareholder/Stockholder/Stock options: Gilead; Advisory/Consultancy: Pfizer, Clovis, Eisai, Boehringer-Ingelheim. L. Pagliaro: Research grant/Funding (institution): Pfizer, Exelixis, Merck, Roche; Travel/Accommodation/Expenses: Merck. U.N. Vaishampayan: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Exeixis. D. Castellano: Advisory/Consultancy: Janssen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, Bristol-Myers Squibb, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre, Boehringer Ingelheim; Research grant/Funding (institution): Janssen Oncology; Travel/Accommodation/Expenses: Pfizer, Roche, Bristol-Myers Squibb, AstraZeneca. Y. Loriot: Honoraria (self): Roche, Astellas, Janssen, Seattle Genetics, AstraZeneca, BMS, MSD, Pfizer, Sanofi, Ipsen; Research grant/Funding (institution), Clinical trial: Roche, BMS, AstraZeneca, MSD, Pfizer, Seattle Genetics, Astellas, Janssen, Clovis, Incyte, Sanofi; Research grant/Funding (institution), Research grant: MSD, Sanofi, Janssen. S. Werneke: Shareholder/Stockholder/Stock options, Full/Part-time employment: Exelixis, Inc., Genentech. D. Curran: Shareholder/Stockholder/Stock options, Full/Part-time employment: Exelixis. T.K. Choueiri: Full/Part-time employment: Dana Farber Cancer Hospital; Leadership role: ASCO; Dana Farber Cancer Hospital; Kidney Cancer Association; KidneyCan; NCCN; Shareholder/Stockholder/Stock options: Pionyr; TEMPEST; Honoraria (self): Alexion Pharmaceuticals; alligent; Analysis Group; ASCO; AstraZeneca; Bayer; Bristol-Myers Squibb; Cerulean Pharma; Clinical Care Options; Corvus Pharmaceuticals; Eisai; EMD Serono; Exelixis; Foundation Medicine; Genentech/Roche; GlaxoSmithKline; Harborsi; Advisory/Consultancy: Alexion Pharmaceuticals; alligent; Analysis Group; ASCO; AstraZeneca; Bayer; Bristol-Myers Squibb; Cerulean Pharma; Clinical Care Options; Corvus Pharmaceuticals; Eisai; EMD Serono; ESMO; Exelixis; Foundation Medicine; GlaxoSmithKline; Harborside Press; H; Research grant/Funding (institution): - Agensys (Inst); Analysis Group (Inst); AstraZeneca (Inst); Bayer (Inst); Bristol-Myers Squibb (Inst); Calithera Biosciences (Inst); Celldex (Inst); Cerulean Pharma (Inst); Congressionally Directed Medical Research Programs (DOD) (Inst); Corvus Pharmaceu; Licensing/Royalties: International Patent Application No. PCT/US2018/058430, entitled “Biomarkers of Clinical Response and Benefit to Immune Checkpoint Inhibitor Therapy; International Patent Application No. PCT/US2018/12209, entitled “PBRM1 Biomarkers Predictive of Anti-Immu; Travel/Accommodation/Expenses: Alexion Pharmaceuticals; alligent; Analysis Group; AstraZeneca; Bayer; Bristol-Myers Squibb; Cerulean Pharma; Clinical Care Options; Corvus Pharmaceuticals; Eisai; EMD Serono; ESMO; Exelixis; Foundation Medicine; GlaxoSmithKline; Harborside Press; Heron; Non-remunerated activity/ies, Medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies such as ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies, Parexel: Medical writing and editorial assistance support may have been funded by Communications companies funded by pharmaceutical companies such as ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies, Parexel. S. Pal: Advisory/Consultancy: Astellas Pharma; Aveo; Bristol-Myers Squibb; Eisai; Exelixis; Genentech; Ipsen; Myriad Pharmaceuticals; Novartis; Pfizer; Research grant/Funding (self): Medivation. All other authors have declared no conflicts of interest.