A phase 2 study of GVAX colon vaccine with cyclophosphamide and pembrolizumab in patients with mismatch repair proficient advanced colorectal cancer

Cancer Medicine

Dwayne L. Thomas II¹  Jennifer N. Durham¹  Noah S. Rozich¹  Robert A. Anders¹  Anna K. Ferguson¹  Nilofer S. Azad¹  Lei Zheng¹  Daniel Laheru¹  Arsen Osipov¹  Elizabeth D. Thompson¹  Ross C. Donehower¹  Elizabeth M. Jaffee¹  Ana De Jesus‐Acosta¹  Adrian G. Murphy¹  Julie M. Nauroth¹  Dung T. Le¹  Christina Rodriguez¹  Qingfeng Zhu¹  Chiung‐Yu Huang¹  Mark Yarchoan¹ 

[1] Bloomberg–Kimmel Institute for Cancer Immunotherapy Johns Hopkins University School of Medicine Baltimore MD USA;

关键词: checkpoint inhibitor;    colorectal cancer;    immunotherapy;    PD-1;    vaccine;   

DOI  :  10.1002/cam4.2763

来源: DOAJ

【 摘 要 】

Abstract Background Mismatch repair proficient (MMRp) colorectal cancer (CRC) has been refractory to single‐agent programmed cell death protein 1 (PD1) inhibitor therapy. Colon GVAX is an allogeneic, whole‐cell, granulocyte‐macrophage colony‐stimulating factor ‐secreting cellular immunotherapy that induces T‐cell immunity against tumor‐associated antigens and has previously been studied in combination with low‐dose cyclophosphamide (Cy) to inhibit regulatory T cells. Methods We conducted a single‐arm study of GVAX/Cy in combination with the PD1 inhibitor pembrolizumab in patients with advanced MMRp CRC. Patients received pembrolizumab plus Cy on day 1, GVAX on day 2, of a 21‐day cycle. The primary endpoint was the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary objectives included safety, overall survival, progression‐free survival, changes in carcinoembryonic antigen (CEA) levels, and immune‐related correlates. Results Seventeen patients were enrolled. There were no objective responses, and the disease control rate was 18% by RECIST 1.1. The median progression‐free survival was 82 days (95% confidence interval [CI], 48‐97 days) and the median overall survival was 213 days (95% CI 179‐441 days). Biochemical responses (≥30% decline in CEA) were observed in 7/17 (41%) of patients. Grade ≥ 3 treatment‐related adverse events were observed in two patients (hemolytic anemia and corneal transplant rejection). Paired pre‐ and on‐treatment biopsy specimens showed increases in programmed death‐ligand 1 expression and tumor necrosis in a subset of patients. Conclusions GVAX/Cy plus pembrolizumab failed to meet its primary objective in MMRp CRC. Biochemical responses were observed in a subset of patients and have not previously been observed with pembrolizumab monotherapy in MMRp CRC, indicating that GVAX may modulate the antitumor immune response.

【 授权许可】

Unknown