Journal article
Phase 2 Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1 Pretreated Metastatic Non-Small Cell Lung Cancer and Metastatic Cutaneous Melanoma
Clinical cancer research, Vol.31(5), pp.848-859
03/03/2025
DOI: 10.1158/1078-0432.CCR-24-1478
PMCID: PMC11873802
PMID: 39786430
Abstract
Purpose: Brentuximab vedotin (BV) is hypothesized to selectively deplete T regulatory cells (Tregs) that express CD30 and re-sensitize tumors to anti-(PD-1) therapy. This study evaluated responses to BV+pembrolizumab post PD-1 and explored corresponding biomarkers. Methods: 55 patients with metastatic non-small cell lung cancer (NSCLC) and 58 with metastatic cutaneous melanoma received ≥1 dose of BV+pembrolizumab. Patients had received a median of 2.0 prior lines of systemic therapies (range, 1-7). The primary endpoint was confirmed objective response rate (ORR). Exploratory endpoints included overall survival (OS) and biomarker analysis in blood and tumor. Results: For the secondary refractory metastatic NSCLC cohort (RECIST v1.1), ORR was 14%, median progression-free survival (PFS) was 5.85 months, and median OS was 14.4 months. For the secondary refractory metastatic cutaneous melanoma cohort (iRECIST), ORR was 24%, median iPFS was 4.44 months, and median OS was 21.9 months. Overall, median duration of OS follow-up was 17.2 months (95% CI 14.62, 22.87). No new safety signals were identified. No treatment-related grade 5 toxicity was seen. Longitudinal immune phenotyping in peripheral blood demonstrated a transient decrease in Tregs. Paired tumor biopsies from baseline and Cycle 3 Day 1 showed a trend of increased CD8 T cell infiltration, especially in responding patients. Conclusions: BV+pembrolizumab in solid tumor malignancies resulted in clinically meaningful, durable responses with encouraging OS and PFS rates supportive of the immunomodulatory activity of this combination. Stronger antitumor activity was observed in secondary refractory cohorts. The safety profile of this combination was consistent with the individual drug risk profiles.
Details
- Title: Subtitle
- Phase 2 Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1 Pretreated Metastatic Non-Small Cell Lung Cancer and Metastatic Cutaneous Melanoma
- Creators
- Sylvia Lee - University of WashingtonOmid Hamid - Angeles Clinic and Research InstituteRobert Jotte - Rocky Mountain Cancer CentersYousef Zakharia - University of Iowa Hospitals and ClinicsTheresa Medina - University of Colorado Anschutz Medical CampusAmanda Gillespie-Twardy - Mountain Blue Cancer Care CenterInderjit Mehmi - Cedars-Sinai Medical CenterSunandana Chandra - Northwestern UniversityGraham Watson - Virginia Oncology AssociatesPatrick Ward - Oncology Hematology CareMarya Chaney - MerckHailing Lu - Metis Design CorporationJason Berndt - PfizerBrian P. O'ConnorKapil Rathi - PfizerEeman Shaikh - PfizerC. Lance Cowey - Baylor University Medical Center
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.31(5), pp.848-859
- DOI
- 10.1158/1078-0432.CCR-24-1478
- PMID
- 39786430
- PMCID
- PMC11873802
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- Pfizer FoundationSeagen, Inc.Ryan Heiser at PfizerPfizerMerck & Co., Inc., Rahway, New Jersey
Thank you to the patients and their families for their participation in the study and to all research personnel for their support of this important trial. This study was sponsored by Seagen, Inc., which was acquired by Pfizer in December 2023. Translational research support was provided by Ryan Heiser at Pfizer. Medical writing support was provided by Lauren Angotti at BioBridges LLC with funding from Pfizer. Direct funding for this research was issued by Seagen Inc. through the joint financial support of Seagen Inc., Bothell, Washington, and Merck & Co., Inc., Rahway, New Jersey.
- Language
- English
- Electronic publication date
- 12/30/2024
- Date published
- 03/03/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984770891202771
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