Abstract 4344
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.
Resources from the same session
4506 - Single intravenous preoperative administration of the oncolytic virus Pexa-Vec to prime anti-tumor immunity
Presenter: Adel Samson
Session: Poster Display session 3
Resources:
Abstract
1631 - Randomized phase 2 clinical trial of NY-ESO-1 protein vaccine combined with cholesteryl pullulan (CHP-NY-ESO-1) in resected esophageal cancer patients
Presenter: Shinichi Kageyama
Session: Poster Display session 3
Resources:
Abstract
4244 - T cell repertoire sequencing reveals dynamics of response to dendritic cell vaccine plus dasatinib for checkpoint blockade resistant metastatic melanoma
Presenter: Luca Quagliata
Session: Poster Display session 3
Resources:
Abstract
5791 - Ixovex, a novel oncolytic E1B-mutated adenovirus
Presenter: Mohiemen Anwar
Session: Poster Display session 3
Resources:
Abstract
4170 - Anti-CSPG4 DNA vaccination as a promising strategy for the treatment of CSPG4+ tumors: a comparative oncology trial
Presenter: Federica Riccardo
Session: Poster Display session 3
Resources:
Abstract
5780 - Antitumor activity, immunogenicity and safety of a novel PD-1 vaccine in combination with two chimeric HER-2 peptide vaccine in syngeneic Balb/c, C57Bl/6 models and in beagle dogs
Presenter: Pravin Kaumaya
Session: Poster Display session 3
Resources:
Abstract
5860 - Maternal immunization against ALK as a weapon to fight neuroblastoma
Presenter: Giuseppina Barutello
Session: Poster Display session 3
Resources:
Abstract
4720 - Phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumors
Presenter: Jason Luke
Session: Poster Display session 3
Resources:
Abstract
5717 - Anti-PD-L1/IL-15 fusion protein generates robust adaptive immune gene signatures in tumors leading to tumor inhibition and memory responses
Presenter: Stella Martomo
Session: Poster Display session 3
Resources:
Abstract
1802 - Evaluation of the anti-tumor efficacy and immune effects of N-809, a novel IL-15 superagonist/anti-PD-L1 bispecific agent
Presenter: Kristin Hicks
Session: Poster Display session 3
Resources:
Abstract