938TiP - Phase II TROPHY-IO-HN study of pembrolizumab ±sacituzumab govitecan in first-line recurrent /metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients

Background

Sacituzumab govitecan (SG) is an antibody-drug conjugate of an anti-Trop-2 antibody linked to the cytotoxic SN-38 payload through a proprietary, hydrolyzable linker. Combining SG with pembrolizumab may improve outcomes for patients with (R/M) HNSCC.

Trial design

TROPHY-IO-HN is a randomized non-comparative phase II study evaluating SG plus pembrolizumab in 1^st line PD-L1 + (CPS≥1) R/M HNSCC. The null hypothesis was that 19% of patients will be alive and progression-free at 1 year. The sample size was calculated under the alternative of an at least 40% rate of patients alive and progression-free at 1 year. Under such assumptions, to account for a power of 90% and a one sided Type I error of 10%, this design will require 33 eligible and evaluable patients allocated to Arm B. Assuming that ∼10 %of patients will be lost to follow up prior to 12 months, 36 patients will be enrolled in Arm B. With a randomization ratio 2:1, 18 patients will be recruited in the pembrolizumab arm A as control for translational research. No formal comparison will be performed between arms. SG will be administered intravenously (IV) at 10 mg/kg on day 1 and 8 until disease progression or unacceptable toxicity, pembrolizumab 200 mg IV on day 1 for up to 35 cycles. The primary endpoint is the progression-free survival (PFS) rate at one year. Key secondary endpoints include overall survival (OS), objective response rate (ORR), and safety. Exploratory endpoints include the association between TROP-2 levels and ctDNA kinetics with outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Gilead, Merck, Hecog.

Disclosure

A. Psyrri: Financial Interests, Personal, Invited Speaker: MSD, Merck Serono, EPICS; Financial Interests, Personal, Advisory Board: Pfizer, Sanofi, MSD, AstraZeneca, BMS, LEO, Rakuten, eTheRNA immunotherapies, Merck Serono, Seagen, Merus, Merus Pharmaceuticals, GSK; Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Pfizer, GSK, Genesis, Incyte, Amgen, Debiopharm, MSD, Janssen, Lilly, Regeneron, Sanofi, BI, Roche, Peregrine, Oncolytics Biotech; Financial Interests, Coordinating PI: AstraZeneca; Financial Interests, Personal and Institutional, Steering Committee Member: Iovance, Pfizer, Roche; Financial Interests, Institutional, Steering Committee Member: Kura Oncology; Financial Interests, Steering Committee Member: Kura Oncology; Financial Interests, Personal and Institutional, Funding: Kura Oncology, BMS, Roche, DEMO, Amgen, BI, Genesis, BMS, Pfizer, Oncolytics Biotech; Financial Interests, Institutional, Funding: Merck Serono, Pfizer, GSK; Financial Interests, Personal, Other, Educational activity: Medscape, PrimeOncology; Financial Interests, Institutional, Local PI: Novartis, Replimmune; Financial Interests, Personal, Steering Committee Member: GSK, Merus pharmaceuticals. All other authors have declared no conflicts of interest.