Safety and Activity of PolyPEPI1018 Combined with Maintenance Therapy in Metastatic Colorectal Cancer: an Open-Label, Multicenter, Phase Ib Study

Joleen M. Hubbard, Eniko R. Toke, Roberto Moretto, Rondell P. Graham, Hagop Youssoufian, Orsolya Lorincz, Levente Molnár, Zsolt Csiszovszki, Jessica L. Mitchell, Jaclynn Wessling, József Tóth, Chiara Cremolini

Research output: Contribution to journalArticlepeer-review


Purpose: Although chemotherapy is standard of care for metastatic colorectal cancer (mCRC), immunotherapy has no role in microsatellite stable (MSS) mCRC, a "cold"tumor. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine derived from 7 tumorassociated antigens (TAA) frequently expressed in mCRC. This study assessed PolyPEPI1018 combined with first-line maintenance therapy in patients with MSS mCRC. Patients and Methods: Eleven patients with MSS mCRC received PolyPEPI1018 and Montanide ISA51VG adjuvant subcutaneously, combined with fluoropyrimidine/biologic following first-line induction with chemotherapy and a biologic (NCT03391232). In Part A of the study, 5 patients received a single dose; in Part B, 6 patients received up to three doses of Poly- PEPI1018 every 12 weeks. The primary objective was safety; secondary objectives were preliminary efficacy, immunogenicity at peripheral and tumor level, and immune correlates. Results: PolyPEPI1018 vaccination was safe and well tolerated. No vaccine-related serious adverse event occurred. Eighty percent of patients had CD8+ T-cell responses against ≥3 TAAs. Increased density of tumor-infiltrating lymphocytes were detected posttreatment for 3 of 4 patients' liver biopsies, combined with increased expression of immune-related gene signatures. Three patients had objective response according to RECISTv1.1, and 2 patients qualified for curative surgery. Longer median progression-free survival for patients receiving multiple doses compared with a single dose (12.5 vs. 4.6 months; P = 0.017) suggested a dose-efficacy correlation. The host HLA genotype predicted multi-antigen- specific T-cell responses (P = 0.01) indicative of clinical outcome. Conclusions: PolyPEPI1018 added to maintenance chemotherapy for patients with unresectable, MSS mCRC was safe and associated with specific immune responses and antitumor activity warranting further confirmation in a randomized, controlled setting.

Original languageEnglish (US)
Pages (from-to)2818-2829
Number of pages12
JournalClinical Cancer Research
Issue number13
StatePublished - Jul 1 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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