Phase 1 study of OCV‐C02, a peptide vaccine consisting of two peptide epitopes for refractory metastatic colorectal cancer

Abstract

Summary OCV‐C02 is a peptide vaccine consisting of two peptide epitopes derived from ring finger protein 43 (RNF43) and translocase of outer mitochondrial membrane 34 (TOMM34). This Phase 1 study assessed the safety, preliminary efficacy and immunological responses following OCV‐C02 administration in patients with advanced or relapsed colorectal cancer who were intolerant or refractory to standard chemotherapy. Primary endpoint was any occurrence of dose‐limiting toxicity (DLT) during cycle 1. Secondary endpoints were treatment‐emergent adverse events, efficacy and immunological responses. Efficacy was evaluated based on overall response rate, disease control rate, time to treatment failure and overall survival. Immunological responses were evaluated by measuring CTL, delayed‐type hypersensitivity (DTH) and regulatory T cells (Tregs). Twenty‐four patients who were HLA‐A*24:02‐positive were enrolled and grouped into four cohorts of six patients each: cohorts 1, 2, 3, and 4 which received s.c. OCV‐C02 (emulsifying agent: Montanide™ ISA 51 VG) 0.3, 1, 3, and 6 mg/body, respectively. After cycle 1, patients who were eligible and willing to continue vaccination proceeded to the extended treatment period. No DLT occurred in cycle 1 and no major safety problems were reported throughout the trial. One patient in cohort 2, three patients in cohort 3 and two patients in cohort 4 achieved stable disease. CTL and DTH responses following vaccination were also observed across the four cohorts. OCV‐C02 at 0.3 to 6 mg/body was found to be safe and well tolerated. Trial registrations: JAPIC clinical trials registry (ID: JapicCTI‐132075) and ClinicalTrials.Gov (ID: NCT01801930).

Colorectal cancer vaccines: Tumor-associated antigensvsneoantigens

“…At first Okuno et al[29] combined chemotherapy with a RNF43 and a 34-kDa translocase of the outer mitochondrial membrane (TOMM34) peptide in a phase I clinical trial which resulted in 83 % stable disease and a mean survival time of 24 mo, but no reduction in tumor burden was observed. The efficiency of inducing specific CTLs by RNF43 and TOMM34 was also proven by additional studies[30,31].…”

Recent Advances on Immune Targeted Therapy of Colorectal Cancer Using bi-Specific Antibodies and Therapeutic Vaccines

“… [ 17 ] melanoma associated antigen (MAGE) only expressed in cancer cells and testis including CRC MAGE-A4 induces an [ 21 ] immune response of CD4+ and CD8+ [ 22 ] mucin 1 (MUC1) Plays roles in self-renewal proliferation and self-renewal, drug-resistance, and anti-apoptosis and also invasion and metastasis of colorectal cancer stem cells [ 23 ] ring finger protein 43 (RNF43) CTL-inducing peptide [ 24 – 26 ] outer mitochondrial membrane (TOMM34) Combined chemotherapy of a RNF43 and TOMM34 peptide showed considerable result in a phase II study. [ 27 , 28 ] …”

Breakthrough concepts in immune-oncology: Cancer vaccines at the bedside

“…Based on these encouraging results, multiple trials have employed this combinatorial strategy but have failed to show any significant clinical effect. For example, a phase II clinical study for patients with resected pancreatic cancer determined that gemcitabine plus OCV‐C02, a 3‐peptide cocktail, had no significant effect on DFS compared to gemcitabine alone 214 . Another strategy explored is the combination of peptide vaccines and ICB because of ICB's ability to intensify immunogenic responses.…”

“…For example, a phase II clinical study for patients with resected pancreatic cancer determined that gemcitabine plus OCV-C02, a 3-peptide cocktail, had no significant effect on DFS compared to gemcitabine alone. 214 Another strategy explored is the combination of peptide vaccines and ICB because of ICB's ability to intensify immunogenic responses. This combination strategy is still in its infancy, and these clinical trials are still ongoing.…”