Abstract 1029TiP
Background
Intratumoral regulatory T-cells (Tregs) contribute to resistance to checkpoint inhibitors through various mechanisms (Saleh 2019). Intratumoral Tregs have a unique phenotype expressing higher levels of CD30 than other T-cells and non-tumor infiltrating Tregs in several malignancies including non-small cell lung cancer (NSCLC; De Simone 2016, Vasanthakumar 2017). BV (ADCETRIS®), a CD30-directed antibody-drug conjugate, has been shown to reduce Tregs in clinical trials of classical Hodgkin’s lymphoma and cutaneous T-cell lymphoma, to be uniquely toxic to CD30-expressing Tregs, and to allow for expansion of co-cultured CD8 T-cells in vitro (Romano 2019, Heister 2018 [AACR]). We plan to evaluate pembro with BV (pembro + BV) in pts that have relapsed after, or who are refractory to, PD-1 inhibition.
Trial design
SGN35-033 (NCT04609566) is a multi-cohort, open-label, multicenter, phase II clinical trial evaluating the efficacy and safety of pembro + BV in pts with metastatic NSCLC (EGFR, ALK, ROS1, and BRAF negative) or metastatic cutaneous melanoma after progression on treatment with PD-1 inhibitor therapy. Enrollment will be based on radiographic-confirmed progression on PD-1 inhibitor therapy. Pts must be aged ≥18 years and on PD-1 therapy currently or had their last dose within 90 days prior to enrollment. ∼60 pts will be assigned to 1 of 4 cohorts (15 pts/cohort) based on disease state and diagnosis. Pts will receive 21-day cycles of pembro + BV. Based on antitumor activity and safety data, each cohort may have an expansion phase (up to an additional 40 pts/cohort) to further characterize the safety and antitumor activity. The primary endpoint is objective response rate (ORR) per investigator assessment (RECIST v1.1). Secondary endpoints include duration of response (DOR) and progression-free survival (RECIST), ORR and DOR (iRECIST), and safety. The observed ORR (RECIST v1.1) and 95% confidence interval will be provided for the full analysis set (all pts who are enrolled and received any amount of study drug) using Clopper-Pearson methodology. Enrollment began in January 2021.
Clinical trial identification
NCT04609566.
Editorial acknowledgement
Anastasija Pesevska, Prime Global.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
C.L. Cowey: Financial Interests, Institutional, Research Grant, Research Funding: Seagen. D.M. Waterhouse: Financial Interests, Institutional, Advisory Role, Consulting or Advisory Role: Bristol-Myers Squibb, AZTherapies, Abbvie, Amgen, McGivney Global Advisors, Janssen Oncology, Seattle Genetics, Jazz Pharmaceuticals, Exelixis, Eisai, EMD Serono, Merck, Pfizer, Mirati Therapeutics; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb, Janssen Oncology, Merck, AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol-Myers Squibb. M.F. Chaney: Financial Interests, Institutional, Full or part-time Employment: Merck; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Merck; Financial Interests, Institutional, Stocks/Shares, And other Ownership Interests: Merck. S. Knowles: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Seagen; Financial Interests, Personal, Other, Other relationship: Seagen; Financial Interests, Institutional, Research Grant, Research Funding: Seagen. All other authors have declared no conflicts of interest.