LBA67 - Cabozantinib (C) plus atezolizumab (A) versus 2nd novel hormonal therapy (NHT) in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC): Final overall survival (OS) results of the phase III, randomized, CONTACT-02 study

Background

Pts with mCRPC whose disease progressed on NHT have a poor prognosis and limited treatments. C+A significantly prolonged progression-free survival (PFS) vs NHT in CONTACT-02 (HR 0.65; 95% CI 0.50, 0.84; P=0.0007), meeting 1 of the study’s 2 primary endpoints. Presented here is the final analysis of the 2nd primary endpoint, OS.

Methods

Pts with mCRPC whose disease progressed on one prior NHT and who had measurable extrapelvic nodal or visceral disease were randomized 1:1 to C+A or NHT (abiraterone + prednisone or enzalutamide). Dual primary endpoints were BIRC-assessed PFS (first 400 pts; PFS ITT) and OS (all randomized pts; ITT).

Results

At the data cutoff (median follow-up 24.0 mo), 575 pts were randomized to C+A (n=289) or NHT (n=286). Baseline characteristics were balanced between treatment arms: 79%/76% had bone metastasis (BM), 23%/23% had liver metastases (LM), and 22%/22% had received prior docetaxel. Follow-on systemic therapy was received in 49% and 56% (36% and 49% received a post-study taxane). Efficacy data are shown, below. Treatment-related grade 3-4 AEs occurred in 40% of the C+A study arm and in 8% of the NHT arm. There were no grade 5 treatment-related AEs. TEAEs led to discontinuation of all treatment components in 17% (C+A) and 15% (NHT). Table: LBA67

Conclusions

CONTACT-02 was a positive study meeting one of the dual primary endpoints of PFS; the combination of cabozantinib and atezolizumab was superior to NHT (HR 0.65). Final OS, the 2nd dual primary endpoint, favored C + A (HR 0.89), but did not achieve statistical significance. A survival advantage was seen in some subgroups (e.g. liver metastasis, bone metastasis) The tolerability profile of C+A was similar to other approved TKI/ICI combinations in pts with advanced cancers.

Clinical trial identification

NCT04446117.

Editorial acknowledgement

Writing and editorial assistance were provided by Stuart Wakelin, PhD of Twist Medical and funded by Exelixis, Inc.

Legal entity responsible for the study

Exelixis, Inc.

Funding

Exelixis, Inc.

Disclosure

N. Agarwal: Financial Interests, Personal, Invited Speaker, Invited speaker: Medscape; Financial Interests, Personal, Invited Speaker, Invited Speaker: Onclive, Research to Practice, Clinical Care Options; Financial Interests, Institutional, Other, I serve in the leadership of my cancer center (Huntsman Cancer Institute, University of Utah. Salt Lake City, UT, USA). There are multiple research projects sponsored by these companies which pay money to my institution: Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GSK, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, Telix, Tracon.; Financial Interests, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharmas with no personal honorarium: AstraZeneca, Calithera, Crispr, Eli Lilly, Exelixis, Immunomedics, Merck, Pfizer,; Financial Interests, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharma companies with no personal honorarium: Merck, Nektar, New Link Genetics, Oric, Pfizer, Prometheus, Rexahn, Takeda, Telix,Tracon; Financial Interests, Trial Chair, One of the two co-chairs of the clinical trials sponsored by these pharma companies. I have not received any honorarium for these roles: Pfizer, Exelixis, Janssen, Telix.; Non-Financial Interests, Member, I am a long-standing member of ASCO and a volunteer. I was awarded the fellow of ASCO in 2023. I also act as the editor of the ASCO Daily News as a volunteer: American Society of Clinical Oncology; Non-Financial Interests, Member, I am a member of this NCI and NCTN-sponsored cooperative clinical trial network group: SWOG; Non-Financial Interests, Member, I am a member of these professional organizations: AACR, AUA, PCF. A.A. Azad: Financial Interests, Personal, Advisory Board: Astellas, Novartis, Sanofi, AstraZeneca, Tolmar, Telix, Merck Serono, Janssen, Bristol Myers Squibb, Ipsen, Bayer, Pfizer, Amgen, Noxopharm, Merck Sharpe Dohme, Daiichi Sankyo, Arvinas; Financial Interests, Personal, Other, Consultant: Aculeus Therapeutics; Financial Interests, Personal, Invited Speaker: Astellas, Janssen, Novartis, Amgen, Ipsen, Bristol Myers Squibb, Merck Serono, Bayer; Financial Interests, Personal, Other, Travel + Accommodation: Astellas, Merck Serono, Amgen, Novartis, Janssen, Tolmar, Pfizer, Bayer; Financial Interests, Personal, Research Grant: Astellas, Merck Serono, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Astellas, Pfizer, Exelixis; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Aptevo Therapeutics, AstraZeneca, GSK, Pfizer, Astellas, SYNthorx, Bionomics, Sanofi, Ipsen, Exelixis, Merck Sharpe Dohme, Janssen, Eli Lilly, Gilead Sciences, Merck Serono, Hinova; Financial Interests, Institutional, Trial Chair: Bayer; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Hinova; Financial Interests, Personal, Trial Chair: Janssen, AstraZeneca; Non-Financial Interests, Leadership Role, Chair, Translational Research Committee: ANZUP Cancer Trials Group; Non-Financial Interests, Leadership Role, Member, Scientific Advisory Committee: ANZUP Cancer Trials Group; Non-Financial Interests, Leadership Role, Chair, Urologic Oncology Committee: Clinical Oncology Society of Australia; Non-Financial Interests, Other, Editorial Board Member: BMC Urology; Non-Financial Interests, Other, Associate Editor: Cancer Research Communications, Frontiers in Oncology. J.C. Galceran: Financial Interests, Personal, Advisory Board: Astellas Pharma, AstraZeneca, Bayer, Johnson & Johnson, MSD Oncology, Novartis (AAA), Roche, Sanofi; Financial Interests, Institutional, Local PI: Janssen-Cilag International NV, Lilly, S.A, Medimmune, Novartis Farmacéutica, S.A, Sanofi-Aventis, S.A; Other, Member of the Commission: Catalan Program of Ambulatory Medication Comission (CAHMDA). N. Matsubara: Financial Interests, Institutional, Research Funding: Janssen, AstraZeneca, Bayer, Roche, MSD, Taiho, Astellas, Amgen, Eisai, Eli Lilly, PRA Health Science, Takeda; Financial Interests, Personal, Financially compensated role, Honoraria: Sanofi. S. Oudard: Financial Interests, Personal, Advisory Board, consultancy, advisory role: Sanofi; Financial Interests, Personal, Invited Speaker, public speaking and advisory role: Janssen; Financial Interests, Personal, Advisory Board, advisory role and public speaking: AstraZeneca, MSD, Merck, Astellas, Ipsen, Pfizer, Roche, Genetech; Financial Interests, Personal, Advisory Board, Advirory board and public speaking: BMS, bayer, Novartis. F. Saad: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Janssen, Pfizer, Myovant, Novartis, AstraZeneca, Merck; Financial Interests, Institutional, Local PI: Novartis, Astellas, bayer, janssen, sanofi, bms, amgen, pfizer, Merck; Financial Interests, Institutional, Coordinating PI: AstraZeneca. A.S. Merseburger: Financial Interests, Personal, Advisory Board, Speaker: Janssen; Financial Interests, Personal, Advisory Board, Speaker, Advisor: Astellas; Financial Interests, Personal, Advisory Board, Advisor: Bayer, Seagen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Member of Board of Directors, Travel costs: EAU. A. Soares: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, Janssen, Roche, Bayer, AstraZeneca, MSD, Bristol Myers Squibb, Adium, Ipsen; Financial Interests, Personal, Other, Honoraria: Janssen, Pfizer, Bayer, AstraZeneca, Merck Serono, Sanofi, Ipsen, Adium; Financial Interests, Personal, Other, Travel Accommodations/Expenses: Bayer, Janssen, Adium, MSD, Merck Serono; Financial Interests, Personal, Officer, Travel Accommodations/Expenses: Ipsen. 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Tsiatas: Financial Interests, Personal and Institutional, Research Funding: AZ, BMS, Daiichi, Exelixis, Gilead, Janssen, Merck, MSD, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas, Bayer, Gilead, Janssen, Ipsen, Merck, MSD, Novartis, Pfizer; Financial Interests, Personal, Financially compensated role, Honoraria: AZ, Astellas, Bayer, Janssen, Ipsen, Merck, MSD; Financial Interests, Personal, Expert Testimony: Astellas, Ipsen; Financial Interests, Personal, Other, Travel Accommodations/Expenses: Janssen, Ipsen, Merck, MSD, Pfizer. S. North: Financial Interests, Personal, Advisory Board, honoraria: Astellas, BMS, Janssen, Merck, Roche, Sanofi, Bayer, AstraZeneca; Financial Interests, Institutional, Local PI, per case funding: Sanofi, AstraZeneca, Ipsen, Astellas. E. Bournakis: Financial Interests, Personal, Invited Speaker: Astellas, Ipsen, Janssen, Sanofi; Financial Interests, Personal, Advisory Board: Astellas, Ipsen, Janssen, Sanofi, Bayer. L. Antonuzzo: Financial Interests, Personal and Institutional, Research Funding: Novartis, AstraZeneca. D.S. Williamson, L. Evilevitch, A. Simmons: Financial Interests, Personal, Full or part-time Employment: Exelixis; Financial Interests, Personal, Stocks or ownership: Exelixis. R. Ferraldeschi: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Stocks/Shares: Roche. P. Nandoskar: Financial Interests, Personal, Full or part-time Employment: Exelixis Inc; Financial Interests, Institutional, Research Funding: Exelixis Inc; Financial Interests, Personal, Other, Travel Accommodations/Expenses: Exelixis Inc; Financial Interests, Personal, Stocks or ownership: Exelixis, BMS. S.K. Pal: Financial Interests, Institutional, Local PI: Eisai, Genentech, Roche, Exelixis, Pfizer, CRISPR Therapeutics, Allogene Therapeutics, Xencor, Novartis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Leadership Role: SWOG; Other, Travel reimbursement: CRISPR, Roche.