4344 - Phase 1 Trial of CV301 in Combination with Anti-PD-1 Therapy in Non-squamous NSCLC

Background

CV301 is an MVA-based vaccine encoding human transgenes MUC1, CEA and TRICOM. A phase I dose-escalation trial (Gatti-Mays E, et al. CCR 2019) concluded that CV301 is safe in advanced cancer patients and generated specific T cell responses against the encoded antigens. Preclinical data supports the rational for combining CV301 with PD-1 inhibitors. The primary objective of this trial was to evaluate safety and tolerability of this combination.

Methods

Patients with advanced non-squamous-NSCLC without actionable alterations in EGFR, ALK and ROS1 were eligible. Two priming doses of MVA-BN-CV301 (MVA) were administered in 4 separate subcutaneous (SC) injections of 4x10^8 IU, 4 weeks apart, followed by boosting doses of Fowlpox-CV301 (FPV) given as a single injection of 1x10^9 IU SC q2w for weeks 9-15, q4w for weeks 19-51 and q13w up to 17 doses for Cohort 1 (C1), q3w for weeks 7-22, q6w for weeks 28-52 and q12w up to 15 doses for Cohort 2 (C2). C1 included patients pre-treated with platinum-containing chemotherapy, who were considered eligible for nivolumab (N; 240 mg IV q2w). C2 included patients receiving frontline treatment with pembrolizumab (P; 200 mg IV q3w) after a minimum of 11 weeks of SD per RECIST.

Results

Between Oct-2017 and Sep-2018, 12 pts were recruited, 4 in C1 and 8 in C2. Median age was 64, and 9 pts were F. Majority of patients were former-smokers (9, 1 current, 2 never). As of Mar-2019 data cut-off, mean treatment duration was 272 days in C1 and 193 days in C2, with 7 pts continuing and 5 discontinuing treatment. Both doses of MVA were administered to 3/4 pts in C1 and 7/8 pts in C2. Median FPV doses/pt: C1=12 and C2=6. CV301 injection-site reactions and flu-like symptoms were observed in all C1 and 7/8 C2 pts. CTCAE ≥ grade 3 AEs were observed in 3/4 C1 and 3/8 C2 pts with 1 fatal TEAE. IRAEs included 1 autoimmune hepatitis, and 1 pneumonitis fulfilling criteria of DLT. As of data-cut, we observed 1 CR (C1), 10 SD, and 1 discontinuation prior to first scheduled RECIST assessment.

Conclusions

The treatment of NSCLC with CV301 + N or P is feasible and tolerated, with no observed increase in the frequency or severity of expected AEs or IRAEs for each component of the combination.

Clinical trial identification

NCT02840994.

Editorial acknowledgement

Legal entity responsible for the study

Bavarian Nordic Inc.

Funding

Bavarian Nordic Inc.

Disclosure

C. Heery: Honoraria (self), Leadership role: Bavarian Nordic. C. Pico-Navarro: Honoraria (self): Bavarian Nordic. M. Piechatzek: Full / Part-time employment: Bavarian Nordic. E. Wagner: Full / Part-time employment: Bavarian Nordic. E. Menius: Full / Part-time employment: Bavarian Nordic. All other authors have declared no conflicts of interest.