LBA24 - Cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results of expanded cohort 6 of the COSMIC-021 study

Background

C may enhance response to immune checkpoint inhibitors by promoting an immune-permissive microenvironment. COSMIC-021 (NCT03170960), a multinational phase 1b study, is evaluating C + A in solid tumors, including mCRPC, which has limited treatment options after failure of novel hormonal therapy (NHT). We report efficacy and safety results of expanded cohort 6 in mCRPC.

Methods

Eligible pts had measurable disease, radiographic progression in soft tissue after enzalutamide and/or abiraterone, and ECOG PS of 0 or 1. Prior chemotherapy for metastatic castration-sensitive prostate cancer (mCSPC) was permitted. Pts received C 40 mg PO QD and A 1200 mg IV Q3W. CT/MRI scans were performed Q6W for 52W and Q12W thereafter. The primary endpoint was ORR by investigator (INV) per RECIST 1.1. Other endpoints included safety, PFS, and OS.

Results

As of the data cutoff of 19 Feb 2021, 132 mCRPC pts were enrolled with a median (range) follow-up of 15.2 mo (5.7, 33.9). Median age was 70 y, 68 (52%) had ECOG PS 0, and 101 (77%) had measurable visceral metastases (mets) and/or extrapelvic lymphadenopathy (EPLN); 42 (32%) had visceral mets and 79 (60%) had EPLN; 33 (25%) had prior docetaxel for mCSPC, and 59 (45%) had received ≥2 prior NHT. Frequent treatment-related adverse events (TRAEs) were diarrhea (55%), nausea (42%), fatigue (43%) and decreased appetite (34%). Grade 3/4 TRAEs occurred in 55%; one grade 5 TRAE of dehydration was reported in a 90 y/o. ORR by INV among all pts per RECIST 1.1 was 23% with 3 CRs; ORR by independent review (BIRC) was 15% (all PRs); DCR (CR + PR + SD) was 84% by INV and 81% by BIRC. In pts with visceral mets and/or EPLN, ORR by INV was 27% with 2 CRs and 18% by BIRC (all PRs); DCR was 88% by INV and 84% by BIRC. Median PFS per RECIST 1.1 by BIRC was 5.7 mo in all pts and 6.8 mo in pts with visceral mets and/or EPLN; median OS was 18.4 mo in both groups. Preliminary data do not suggest an association between tumor PD-L1 status (known for 75 pts) and anti-tumor activity.

Conclusions

C + A demonstrated clinically meaningful activity with a manageable safety profile in mCRPC, supporting a phase 3 study of C + A versus second NHT (CONTACT-02; NCT04446117).

Clinical trial identification

XL184-021; NCT03170960.

Editorial acknowledgement

Medical writing assistance provided by Julie Lougheed, PhD (Exelixis, Inc.).

Legal entity responsible for the study

Exelixis.

Funding

Exelixis.

Disclosure

N. Agarwal: Financial Interests, Personal, Other, Advisory Board, Honoraria: Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Advisory Board, Honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: Bavarian Nordic; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Other, Advisory Board, Honoraria: Bayer; Financial Interests, Institutional, Research Grant: BN immunotherapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Other, Advisory Board, Honoraria: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Calithera; Financial Interests, Institutional, Other, Advisory Board, Honoraria: Calithera; Financial Interests, Research Grant: Celldex; Financial Interests, Institutional, Research Grant: Clovis; Financial Interests, Personal, Other, Advisory Board, Honoraria: Clovis; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Other, Advisory Board, Honoraria: Eisai; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Personal, Other, Advisory Board, Honoraria: Eli Lilly; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Personal, Other, Advisory Board, Honoraria: EMD Serono; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Personal, Other, Advisory Board, Honoraria: Exelixis; Financial Interests, Personal, Other, Advisory Board, Honoraria: Foundation Medicine; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Personal, Other, Advisory Board, Honoraria: Genentech; Financial Interests, Institutional, Research Grant: Glaxo Smith Kline; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Personal, Other, Advisory Board, Honoraria: Janssen; Financial Interests, Institutional, Research Grant: Medivation; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Other, Advisory Board, Honoraria: Merck; Financial Interests, Institutional, Research Grant: Nektar; Financial Interests, Personal, Other, Advisory Board, Honoraria: Nektar; Financial Interests, Institutional, Research Grant: New Link Genetics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Other, Advisory Board, Honoraria: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Advisory Board, Honoraria: Pfizer; Financial Interests, Personal, Other, Advisory Board, Honoraria: Pharmacyclics; Financial Interests, Institutional, Research Grant: Prometheus; Financial Interests, Institutional, Research Grant: Rexahn; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Personal, Other, Advisory Board, Honoraria: Seattle Genetics; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Tracon; Financial Interests, Personal, Other, Advisory Board, Honoraria: Aveo; Financial Interests, Personal, Other, Advisory Board, Honoraria: MEI Pharma. B.A. McGregor: Financial Interests, Personal, Advisory Role: Pfizer, Exelixis, Astellas, Seattle Genetics, EMD Serono, Eisai, Dendreon, BMS, Calithera; Financial Interests, Personal and Institutional, Sponsor/Funding: Exelixis, BMS, Seattle Genetics, Calithera, Pfizer. B.L. Maughan: Financial Interests, Personal, Advisory Role: AVEO oncology, Janssen, Astellas, Bristol Myers Squibb, Clovis, Tempus, Merck, Exelixis, Bayer Oncology and Peloton Therapeutics; Financial Interests, Institutional, Research Grant: Exelixis, Bavarian-Nordic, Clovis, Genentech and Bristol Myers Squibb. T. Dorff: Financial Interests, Personal, Advisory Role: AstraZeneca; Bayer; Bristol Myers Squibb; Janssen Oncology; Noxopharm; Roche; Seattle Genetics; Financial Interests, Personal, Speaker’s Bureau: Exelixis; Prometheus; Financial Interests, Personal and Institutional, Research Grant: Bayer; Bristol Myers Squibb. B. Fang: Financial Interests, Institutional, Full or part-time Employment: NYU School of Medicine; Financial Interests, Personal, Full or part-time Employment: Regional Cancer Care Associates; Financial Interests, Personal, Stocks/Shares: Regional Cancer Care Associates. R. McKay: Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Dendreon, Exelixis, Janssen, Merck, Novartis, Pfizer, Sanofi, and Tempus; Financial Interests, Personal, Advisory Role: Myovant, Vividion; Financial Interests, Personal, Other, Honoraria: Bayer, BMS, Exelixis, Merck; Financial Interests, Personal, Research Grant: Pfizer, Tempus, Bayer; Financial Interests, Personal, Other, Molecular tumor board member: Caris. P. Singh: Financial Interests, Personal, Advisory Role: EMD soreno. R. Dreicer: Financial Interests, Personal, Advisory Role: Astellas, Bayer, Exelixis, EMD Serono Gilead, Hinova, Infinity, Janssen, Merck, Myovant, Pfizer, Propella, Tavanta, Veru; Financial Interests, Personal, Funding: BMS, Seagen, Arvinas. S. Srinivas: Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Speaker’s Bureau: Genentech; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb (Inst); Exelixis (Inst); Genentech (Inst); Merck . Y. Loriot: Financial Interests, Personal and Institutional, Advisory Role: Astellas Pharma; AstraZeneca; Bristol Myers Squibb; Clovis Oncology; Janssen; Janssen (Inst); MSD Oncology; MSD Oncology (Inst); Roche; Seattle Genetics; Financial Interests, Institutional, Funding: AstraZeneca (Inst); Boehringer Ingelheim (Inst); Clovis Oncology (Inst); CureVac (Inst); Exelixis (Inst); Incyte (Inst); Janssen Oncology (Inst); Medivation (Inst); MSD Oncology (Inst); Nektar (Inst); Oncogenex (Inst); Pfizer (Inst); Sanofi (Inst); Financial Interests, Personal, Other, Travel, Accommodations, and/or Expenses: Astellas Pharma; AstraZeneca; Janssen Oncology; MSD Oncology; Roche; Seattle Genetics. U.N. Vaishampayan: Financial Interests, Personal, Advisory Role: Exelixis, Merck, BMS, Bayer; Financial Interests, Personal, Other, Honoraria: Exelixis, Bayer, Merck, BMS; Financial Interests, Personal and Institutional, Research Grant: BMS, Merck, Astellas. S. Goel: Financial Interests, Institutional, Research Grant: BeiGene (Inst); Oncolytics (Inst); Financial Interests, Personal, Other, a patent with a co-inventor, John Mariadason, Ph.D, entitled: See notes. D. Curran: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc. A. Panneerselvam: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc. L. Liu: Financial Interests, Personal, Full or part-time Employment: Exelixis, Inc.; Financial Interests, Personal, Stocks/Shares: Exelixis, Inc. T.K. Choueiri: Financial Interests, Personal, Full or part-time Employment: - Dana Farber Cancer Hospital; Financial Interests, Personal, Leadership Role: ASCO; Dana Farber Cancer Hospital; KidneyCan; NCCN; Financial Interests, Personal, Other, Honoraria: 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; Financial Interests, Personal, Advisory Role: 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; Financial Interests, Institutional, Funding: - 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; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: 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; Financial Interests, Personal, Other, Travel, Accommodations, 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; Financial Interests, Personal, Other, Medical writing and editorial assistance support: ClinicalThinking, Health Interactions, Envision Pharma Group, Fishawack Group of Companies, Parexel. S.K. Pal: Financial Interests, Personal, Advisory Role: Astellas Pharma; Aveo; Bristol Myers Squibb; Eisai; Exelixis; Genentech; Ipsen; Myriad Pharmaceuticals; Novartis; Pfizer. All other authors have declared no conflicts of interest.