1883MO - MEDI5752 (volrustomig), a novel PD-1/CTLA-4 bispecific antibody, in the first-line (1L) treatment of 65 patients (pts) with advanced clear cell renal cell carcinoma (aRCC)

Background

PD-1/CTLA-4 inhibition has improved survival in aRCC but maximizing the potential benefit of CTLA-4 inhibition is limited by toxicity. MEDI5752 (volrustomig) is designed to fully inhibit PD-1 while preferentially inhibiting CTLA-4 on activated PD-1+ T cells. This first-time-in-human trial showed encouraging activity with volrustomig 1500 mg in 1L aRCC. We present data from the 750 mg and 500 mg cohorts (M750 and M500).

Methods

Treatment-naïve pts with aRCC received M750 mg or M500 mg every 3 weeks until disease progression or unacceptable toxicity. The primary objective was objective response rate (ORR).

Results

In M750 (n=32)/M500 (n=33), 75.0/63.6% had IMDC I/P risk. Median duration of follow-up in M750/M500 was 15.9 (range, 2.2-20.4)/8.6 (1.6-14.7) months. ORR was similar in M750/M500 (46.9%/45.5%), with higher CR rate/DCR and longer mPFS in M750 (Table). The median duration of response (DOR) was 13.2/8.4 months; mDOR in pts who discontinued due to AE was not reached in M750. Grade 3-4 immune-related adverse events (irAEs) were higher at M750 (46.9% vs 24.2%), although nearly half of events did not require steroids and nearly all non-endocrine irAEs resolved. There was increased T cell proliferation at both doses and greater T cell activation in M750 vs M500.

Conclusions

Volrustomig is a novel bispecific antibody with high degree of efficacy in 1L aRCC and across IMDC risk groups, with a low rate of upfront treatment failure. The safety profile is consistent with dual checkpoint inhibition. Volrustomig with lenvatinib is also being evaluated in 1L aRCC (NCT04522323).

Table: 1883MO

Per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. CI, confidence interval; CR, complete response; DCR, disease control rate; F, favorable; IMDC, International Metastatic RCC Database Consortium; I/P, intermediate/poor; mPFS, median progression free survival; NE, not estimable.

Clinical trial identification

NCT03530397.

Editorial acknowledgement

Medical editing support for the development of this abstract, under the direction of the authors, was provided by Steve Hill, PhD, of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M.H. Voss: Financial Interests, Personal, Invited Speaker: Ideology Health, WebMD, MedNet, Talemhealth, Onclive, Axiom, Clinical Care Options; Financial Interests, Personal, Advisory Board: Eisai, Exelixis, Merck, Calithera, Aveo, Genentech, Oncorena, Affimed, MICU Rx; Non-Financial Interests, Principal Investigator: AstraZeneca, Pfizer, Merck, Genentech; Financial Interests, Funding: Pfizer; Financial Interests, Personal, Advisory Role: Affimed, Aravive, onQuality, mmunitybio, AstraZeneca, Mertelsmann Foundation , Genentech, Merck. B. Garmezy: Financial Interests, Institutional, Research Grant: AbbVie, AstraZeneca, CRISPR Therapeutics, Exelixis, Genentech, Janssen, Loxo Oncology, Arcus Biosciences, Xencore, Aveo, Zenshire, Accutar Biotechnology, Kinnate Biopharma, Jubilant Therapeutics, Janux Therapeutics, Mix Therapeutics, Nuvation Bio, Profound Bio, Kineta; Financial Interests, Institutional, Other, Consulting: Amgen, Arvinas, Aveo, Bayer, Exelixis, Janssen, Merck, Sanofi-Aventis. J.P. Maroto Rey: Financial Interests, Personal, Advisory Role: Astellas, Ipsen, BMS, Merck/Pfizer, Bayer, Janssen; Financial Interests, Personal, Other, Travel: Merck/Pfizer. A. Rodriguez-Vida: Financial Interests, Personal, Invited Speaker: Roche, BMS, Janssen, AstraZeneca Ipsen; Financial Interests, Personal, Advisory Board: MSD, Pfizer, Astellas, Bayer, Merck. J. Oliveira: Financial Interests, Personal, Other, Advisory board, Invited speaker: AstraZeneca, Roche, Novartis, Janssen; Financial Interests, Personal, Invited Speaker: GSK, BMS, MSD, Bayer; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Funding, Investigator Initiated Clinical Trial funding: AstraZeneca. S. Negrier: Financial Interests, Personal, Advisory Board: Pfizer, BMS, Ipsen, MSD, Eisai; Financial Interests, Institutional, Research Grant: Pfizer, Ipsen; Other, Other, Reimbursement of travel costs + Congress registration: Pfizer, Ipsen, MSD; Other, Other, Reimbursement of travel costs: BMS, Eisai. B. Tran: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Astellas, Bayer, BMS, Ipsen, IQVIA, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, Tolmar, Sanofi Ammunix; Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, Bayer, BMS, Merck, Pfizer; Financial Interests, Institutional, Research Grant: Amgen, Astellas, AstraZeneca, Bayer, BMS, Genentech, Ipsen, Janssen, Pfizer, MSD; Financial Interests, Personal, Steering Committee Member: CG Oncology, Janssen, MSD. B.A. Carneiro: Financial Interests, Institutional, Research Grant: AstraZeneca, AbbVie, Actuate Therapeutics, Astellas, Bayer, Dragonfly Therapeutics, Pfizer, Repare Therapeutics; Financial Interests, Personal, Advisory Board: Foundation Medicine, Seattle Genetics. E. Castanon Alvarez: Financial Interests, Personal, Advisory Board: MSD, Roche, BMS; Financial Interests, Personal, Invited Speaker: GSK; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Roche, MSD, GSK, ARC. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Daiichi Sankyo; Financial Interests, Personal, Steering Committee Member: Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Indivumed, AstraZeneca; Financial Interests, Other, Durg supply for clinical trial: Merck; Financial Interests, Institutional, Coordinating PI, Drug supply for clinical trial: MSD; Financial Interests, Institutional, Local PI, drug supply for clinical trial: zy,meworks; Financial Interests, Institutional, Local PI, drug supply for clinical trial: Beigine; Financial Interests, Coordinating PI, Drug supply for clinical trial: Incyte. Y. Wang, S.D. Gainer, J.M. Asare: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. Z. Tang, I. Achour: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, BMS, Eisai, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche; Non-Financial Interests, Principal Investigator, Clinical trial steering committee: Pfizer, BMS, AVEO, AstraZeneca, MSD; Non-Financial Interests, Principal Investigator: Ipsen; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU). All other authors have declared no conflicts of interest.