1979P - phase I trial of pembrolizumab in HIV-associated Kaposi sarcoma (KS)

Background

Cancer Immunotherapy Trials Network 12, a phase 1 multicenter study of pembrolizumab (pembro) in advanced HIV-associated cancers showed safety across a range of cancers in patients (pts) with controlled HIV (Uldrick et al. JAMA Oncology 2019 ). We report results from the expanded KS cohort.

Methods

Pts with HIV+ KS, CD4 count (CD4) ≥50 cells/μL, antiretroviral therapy (ART) for ≥4 weeks, HIV viral load ≤200 copies/mL with or without prior KS therapy were eligible. Pts received pembro 200 mg q3 weeks for up to 35 cycles. The primary objective was safety by NCI Common Terminology Criteria for Adverse Events; the secondary objective was KS response rate by AIDS Clinical Trials Group Criteria. Progression-free survival (PFS) and duration of response (DOR) were evaluated by Kaplan-Meier (KM) methodology.

Results

32 men [median (med) age 45 years; 16 White, 15 Black, 7 Latino] with HIV+ KS were enrolled. Baseline med CD4 was 274 cells/μL. 9 pts had no prior systemic KS therapy. Pts received a med of 10 cycles of pembro. 2 pts completed 35 cycles and/or 2 years of treatment, 6 have ongoing treatment, and 24 stopped treatment before 35 cycles [progressive disease (9), unacceptable toxicity (5), declined further treatment (3), death (1), other reasons (6)]. Med CD4 increase at end-of-treatment was 50 cells/μL (p=0.046). 13 pts (41%) had grade (G) ≥2 pembro-related treatment-emergent adverse events (AE), including 1 previously reported pt who died of polyclonal HHV8-related B cell lymphoproliferation. 10 (31%) pts had ≥1 immune-mediated AE (imAE) [G1 (1), G2 (5), G3 (4)] with 7 (22%) requiring systemic steroids. Of the 28 evaluable pts, 17 had a partial response (including 6 with CD4 <200 cells/μL), 8 had stable disease, and 3 had progressive disease as best response to pembro. The overall response rate (ORR) was 60.7% (95% CI: 40.6-78.5) and did not differ by CD4. Notably, the ORR was 85.7% (95% CI: 42.1-99.6) in pts without prior KS therapy. Med PFS was 28.2 mo (95% CI: 4.2-non-calcuable). The KM probability estimate of a DOR ≥ 12 months was 91.7% (95% CI: 53.9-98.7).

Conclusions

Pembro leads to a durable, high response rate, particularly as first systemic KS therapy, and is associated with CD4 immune reconstitution. Although 31% of pts had imAEs, they were successfully managed following standard guidelines.

Clinical trial identification

NCT02595866.

Editorial acknowledgement

Legal entity responsible for the study

Fred Hutchinson Cancer Center.

Funding

National Cancer Institute of the National Institutes of Health and Merck Sharp & Dohme Corp.

Disclosure

K. Lurain: Financial Interests, Institutional, Other, Financial support to NCI for clinical trial: BMS, CTI BioPharma, EMD Serrono; Financial Interests, Institutional, Other, Drug supplied for clinical trial: Merck, Eli Lily; Financial Interests, Institutional, Other, Drug supplied for preclinical studies: Lentigen; Financial Interests, Institutional, Other, Financial support to NCI for preclinical studies: Janssen. R. Ramaswami: Financial Interests, Institutional, Other, Collaborative agreement for funding of clinical trial: BMS-Celgene; Financial Interests, Institutional, Other, Collaborative agreement for supply of study drug for clinical trial: CTI Biopharma; Financial Interests, Institutional, Other, Collaborative research agreement for funding of study to institution.: EMD-Serono. G. Goyal: Financial Interests, Personal, Advisory Board: Opna Bio LLC; Financial Interests, Personal, Other, Consultancy: 2nd.MD; Financial Interests, Institutional, Local PI: Sutro Biopharma, Viracta therapeutics, SeaGen. M. Menon: Financial Interests, Institutional, Coordinating PI, Research funds to my institution: Cepheid, Roche; Financial Interests, Institutional, Coordinating PI, Research Funds to my institution: GSK; Non-Financial Interests, Member: American Society of Clinical Oncology (ASCO). M. Wagner: Financial Interests, Personal, Advisory Board, Scientific advisory board: Adaptimmune, Deciphera, Epizyme, Aadi. N. Bhardwaj: Financial Interests, Personal, Advisory Board: Novartis, curevac, Breakbio, Genotwin, carisma, ATP; Financial Interests, Institutional, Full or part-time Employment, Professor of Hematology and Oncology: Icahn School of Medicine; Financial Interests, Personal, Full or part-time Employment, extramural member: Parker Institute for Cancer therapy; Financial Interests, Personal, Stocks/Shares: Apricity, Primevax, Vaccitech, Rome therapeutics; Financial Interests, Personal, Other, licensed technology: CellBioengines; Financial Interests, Institutional, Coordinating PI: Merck; Non-Financial Interests, Principal Investigator, grants: NIH; Other, Other, Board of Directors: AACR; Other, Other, Boards of Scientific Councillors: Cancer Research Institute. M. Abdul-Hay: Financial Interests, Personal, Advisory Board: Takeda, Incyte, Kite, Jazz, Daiichi Sankyo, Rigel; Financial Interests, Institutional, Coordinating PI: Janssen; Financial Interests, Institutional, Local PI: servier, Janssen. R. Yarchoan: Financial Interests, Institutional, Other, CRADA with NCI to do preclinical and clinical research. Funds, drug, and proprietary information provided.: BMS; Financial Interests, Institutional, Other, Drug to NCI for clinical trial.: Merck and Co.; Financial Interests, Institutional, Other, Drug and proprietary information to NCI under CRADA in support of clinical trial.: EMD Serono; Financial Interests, Institutional, Other, Drug and proprietary information to NCI in support of clinical trial: Eli Lilly; Financial Interests, Institutional, Other, CRADA with NCI providing funds, proprietary information, and drug to support preclinical and clinical research.: CTI Biopharma; Financial Interests, Institutional, Other, Drug and proprietary information to conduct preclinical research.: Janssen Pharmaceutical; Other, Other, R. Yarchoan is a co-inventor on US Patent 10,001,483 entitled: NIH. S.P. Fling: Financial Interests, Institutional, Funding, Industry provided funds in salary support and research for CITN clinical trials.: Merck, Revimmune. Q. Lu: Financial Interests, Institutional, Full or part-time Employment, I am the employee of the above company which was compensated for the works I did (including statistical analysis and review of abstract) for this submitted abstract: Cytel Singapore Pte. Ltd., Singapore. T.S. Uldrick: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron; Financial Interests, Institutional, Coordinating PI, Supported clinical trial.: Merck, Roche; Financial Interests, Institutional, Other, Supported clinical trial: Celgene/BMS. All other authors have declared no conflicts of interest.