Abstract
Phase 2 open-label study of brentuximab vedotin (BV) + pembrolizumab (pembro) in patients (pts) with treatment (tx)-naive metastatic head and neck squamous cell carcinoma (HNSCC)
Journal of clinical oncology, Vol.43(16_suppl), pp.6015-6015
06/2025
DOI: 10.1200/JCO.2025.43.16_suppl.6015
Abstract
6015
Background: BV, an antibody-drug conjugate (ADC) targeting CD30, is hypothesized to deplete T regulatory cells (Tregs) that express CD30 and resensitize tumors to anti–PD-1 therapy. SGN35-033 (NCT04609566) is an ongoing multicohort study evaluating the efficacy and safety of BV + pembro in pts with solid tumors; we report results for cohort 6 in tx-naive HNSCC with PD-L1 combined positive score (CPS) ≥1, where pembro has historically demonstrated ORR of 19% and mPFS of 3.2 months. Methods: Cohort 6 included pts with metastatic HNSCC with PD-L1 CPS ≥1 by local testing and no prior therapy for metastatic disease or exposure to a PD-1/PD-L1 inhibitor. Pts received BV 1.8 mg/kg + pembro 200 mg every 3 wks. The primary endpoint was confirmed ORR assessed by investigator per RECIST 1.1. Secondary endpoints included DOR, PFS, and safety. Exploratory endpoints included OS and biomarker analyses. A genAI tool (01/02/25; Pfizer; GPT-4o) developed the 1st draft; authors assume content responsibility. Results: As of 10/25/24, 32 pts received ≥1 dose of BV + pembro. In all pts, the confirmed ORR was 34% (95% CI, 18.6-53.2), with median follow-up duration of 9.7 mo and median DOR not reached (95% CI, 3.9 mo-not estimable [NE]). BOR is in the Table. Responses were seen regardless of HPV status and across PD-L1 CPS ≥1 subgroups, with responses in 11 of 32 (34%) vs 9 of 25 (36%) in CPS ≥1 vs CPS ≥20, respectively. The KM estimate of DOR ≥6 mo was 89%. Median PFS was 7.2 mo (95% CI, 3.2 mo-NE); 6-mo PFS rate was 56%. Biomarker analyses of peripheral blood showed that Tregs expressed relatively higher CD30 vs other T cells. There was a trend of Treg depletion and increased T-cell proliferation and activation after BV + pembro. Observed PK of BV when combined with pembro in HNSCC was similar to that of BV monotherapy. All pts had ≥1 tx-emergent adverse event (TEAE); 24 pts (75%) had a grade ≥3 TEAE; 10 pts (31%) had tx-related grade ≥3 TEAEs. The most common tx-related grade ≥3 TEAEs were lymphocyte count decreased (13%), ALT increased, fatigue, neutropenia, and neutrophil count decreased (6% each). Tx-related serious TEAEs were reported in 2 pts (6%). No new safety signals were identified. Conclusions: BV + pembro demonstrated promising clinical efficacy with a safety profile consistent with each individual agent in pts with tx-naive metastatic HNSCC with PD-L1 CPS ≥1. Biomarker analyses support the hypothesized immunomodulatory mechanism of action of BV + pembro. These encouraging data are consistent with prior findings in PD-1–refractory NSCLC and melanoma and support continued investigation of CD30-directed ADCs + anti–PD-1 therapy in solid tumors. Clinical trial information: NCT04609566 . n=32 BOR, n (%) a Complete response 1 (3) Partial response (PR) 10 (31) Stable disease 12 (38) PD 5 (16) a 1 pt (3%) had unconfirmed PR at data cutoff; 3 pts (9%) discontinued tx with no postbaseline response assessment.
Details
- Title: Subtitle
- Phase 2 open-label study of brentuximab vedotin (BV) + pembrolizumab (pembro) in patients (pts) with treatment (tx)-naive metastatic head and neck squamous cell carcinoma (HNSCC)
- Creators
- Cristina P. Rodriguez - Fred Hutch Cancer CenterSylvia Lee - Fred Hutch Cancer CenterGraham Watson - The US Oncology NetworkAmanda Lynn Gillespie-Twardy - The US Oncology NetworkDouglas Earl Laux - University of IowaPatrick J. Ward - The US Oncology NetworkJeffrey Yorio - The US Oncology NetworkOmar Khaled Abughanimeh - University of Nebraska Medical CenterJ. Thaddeus Beck - Highlands Oncology GroupKevin Kim - PfizerHailing Lu - PfizerJason Berndt - PfizerMarya F. Chaney - MerckEeman Shaikh - PfizerErin R. Alesi - Virginia Commonwealth University
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.43(16_suppl), pp.6015-6015
- DOI
- 10.1200/JCO.2025.43.16_suppl.6015
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 06/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984843586502771
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