1994P - Updated efficacy profile of the double antibody drug conjugate (DAD) phase I trial: Sacituzumab govitecan (SG) plus enfortumab vedotin (EV) in ≥ second line in metastatic urothelial carcinoma (mUC)

Background

SG and EV are both approved for treatment-resistant mUC. We previously reported the safety and efficacy for combination of SG+EV in a phase I trial. Here, we present updated efficacy outcomes with a nearly 2 years of follow-up.

Methods

Patients (pts) with mUC and ECOG performance status ≤1 who progressed on platinum and immune checkpoint inhibitor (ICI) or were cisplatin ineligible and received one line of therapy were enrolled using a Bayesian Optimal Interval approach. SG and EV were dosed on D1,8 of a 21-day cycle until progression of unacceptable toxicity at 3 dose levels (DLs). The primary endpoint was safety and secondary endpoints included objective response rate (ORR), progression free survival (PFS) and overall survival (OS).

Results

Between May 2021 and April 2023, 24 pts were enrolled (9 DL1, 9 DL2, 6 DL3. 22/23 pts received prior platinum and ICI, 11 pts received ≥ 3 lines of therapy. DL2 (SG 8 mg/kg + EV 1.25 mg/kg) was the recommended phase 2 dose. At time of data cutoff on April 8 2024, median follow-up was 22 months (range up to 34 months). Median number of cycles administered for SG+EV was 11 (range 1-22+). ORR was 70% (16/23, 95% Confidence interval (CI) 47-87%); 3 pts experienced progressive disease as best response. 7 pts had >70% shrinkage of which 4 were complete responses. Median duration of response was 10 months (range 3-33+) with ongoing responses in 6 pts. Median PFS was 8.9 months (95% CI: 4.8-11.8). 12-month OS rate was 78% (95% CI: 55-90). There were no new safety signals or unexpected delayed toxicities. Table: 1994P

Conclusions

With 22 month median follow-up, SG+EV continues to show encouraging activity with an ORR of 70% with no new safety signals in ps with treatment resistant mUC. This data supports the ongoing expansion cohorts of SG 7.5 mg/kg + EV 1.25 mg/kg D1,8 every 21 days in the treatment-resistant setting and in combination with pembrolizumab as first-line therapy for mUC (NCT04724018).

Clinical trial identification

NCT04724018.

Editorial acknowledgement

Legal entity responsible for the study

Dana-Farber Cancer Institute.

Funding

Gilead.

Disclosure

B.A. McGregor: Financial Interests, Personal, Advisory Board: Exelixis, BMS, Dendreon, Seagen, Astellas, Eisai, Pfizer, Gilead, Arcus, Loxo/Lily; Financial Interests, Personal, Invited Speaker: EMD Serono, Seagen; Financial Interests, Institutional, Trial Chair: Pfizer, Exelixis, Exelixis, BMS, Gilead; Financial Interests, Institutional, Local PI: Calithera, Seagen, Aveo; Non-Financial Interests, Member: ASCO. G.P. Sonpavde: Financial Interests, Personal, Advisory Board: EMD Serono, Bristol Myers Squibb, Genentech, Merck, Seattle Genetics, Exelixis, Janssen, Bicycle Therapeutics, Gilead, Scholar Rock, G1 Therapeutics, Loxo Oncology, Lucence, Tempus, Syapse, Astellas, Pfizer, Atkis, Kura, Syncorp, Vial, PrecisCa; Financial Interests, Personal, Advisory Board, Editor of Bladder cancer virtual center of excellence for Practice Update: Elsevier; Financial Interests, Personal, Other, Member of data safety monitoring board: Mereo; Financial Interests, Personal, Other, Author of chapter: Uptodate; Financial Interests, Personal, Invited Speaker: Research to practice, Seattle Genetics, Gilead, Exelixis, Janssen, Astellas, Merck, Aveo, Pfizer, Natera, Bayer, PeerView, Ideology Health, Grand Rounds in Urology, Onviv; Financial Interests, Personal, Advisory Board, to develop a trial in bladder cancer: Servier Pharmaceuticals; Financial Interests, Personal, Advisory Board, Investigational drug development for HER2+ cancers: Daiichi Sankyo/AstraZeneca; Financial Interests, Institutional, Research Grant: Gilead, EMD Serono, Jazz Pharma; Financial Interests, Institutional, Local PI: BMS; Non-Financial Interests, Principal Investigator, Steering committee of trial: Bristol Myers Squibb; Non-Financial Interests, steering committee of trial: Merck; Other, Spouse employment: Myriad Genetics; Other, Travel: BMS, Astellas. X. Gao: Financial Interests, Personal, Advisory Board: Bayer, Flare Therapeutics, Silverback Therapeutics, PureTech, PathAI, Arvinas, Loxo Oncology; Financial Interests, Institutional, Local PI: Arvinas, Exelixis, Harpoon Therapeutics, Aprea Therapeutics, Takeda, Aravive, Merck, Poseida Therapeutics, TopAlliance BioSciences, Novartis, Regeneron, ALX Oncology, Flare Therapeutics, Nuvation Bio, Loxo Oncology; Financial Interests, Institutional, Coordinating PI: Bayer. S. Berg: Financial Interests, Personal, Advisory Board: Pfizer, Exelixis. C. Mantia: Financial Interests, Personal, Advisory Board, I participated in a one-time advisory board: Aadi Bioscience; Financial Interests, Personal, Advisory Board, One time advisory board: Synthekine; Financial Interests, Personal, Other, One time consulting: Nextech; Financial Interests, Personal, Other, Consulting: Cogent; Financial Interests, Institutional, Coordinating PI, Institutional funding for research: Bristol Myers Squibb. X.X. 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Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; 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All other authors have declared no conflicts of interest.