TY - JOUR
T1 - Phase 1 trial of CV301 in combination with anti-PD-1 therapy in nonsquamous non-small cell lung cancer
AU - Rajan, Arun
AU - Gray, Jhanelle E.
AU - Devarakonda, Siddhartha
AU - Birhiray, Ruemu
AU - Korchin, Borys
AU - Menius, Erika
AU - Donahue, Renee N.
AU - Schlom, Jeffrey
AU - Gulley, James L.
N1 - Funding Information:
This research was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health and via a Cooperative Research and Development Agreement (CRADA) between the NCI and Bavarian Nordic.
Funding Information:
Jhanelle E. Gray—Dr. Gray reports grants and personal fees from AstraZeneca, Bristol‐Myers Squibb, Merck and Novartis, grants from Boehringer Ingelheim, Genentech, G 1 Therapeutics, Pfizer and the Ludwig Institute of Cancer Research, personal fees from Blueprint Medicines, EMD Serono—Merck KGaA, Inivata and Janssen Scientific Affairs, LLC, and nonfinancial support from Daiichi Sankyo, Inc., outside the submitted work.
Publisher Copyright:
© 2022 UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - CV301, a poxviral-based vaccine, has been evaluated in a phase 1 clinical trial (NCT02840994) and shown to be safe and immunologically active (phase 1a). Preclinical data support a combination of CV301 with programmed death-1 inhibitors, which has been evaluated in the phase 1b part of this trial and is reported here. Patients with advanced nonsquamous non-small cell lung cancer (NSCLC) without actionable genomic alterations received two priming doses of modified vaccinia Ankara-BN-CV301 (MVA) 4 weeks apart, followed by boosting doses of fowlpox-CV301 (FPV) at increasing time intervals for a maximum of 17 doses in combination with nivolumab for cohort 1 (C1) and 15 doses in combination with pembrolizumab for cohort 2 (C2). The primary objective was evaluation of safety and tolerability. Between October 2017 and September 14, 2018, patients were enrolled (C1: 4; median age: 64 years). Mean treatment duration was 332 days in C1 and 289 days in C2. CTCAE ≥grade 3 adverse events (AEs) were observed in four (100%) patients in C1 and three (37.5%) patients in C2. There was one death on trial. Immune-related AEs (irAEs) fulfilling criteria for a dose-limiting toxicity included 1 case of pneumonitis. Among 11 evaluable patients, 1 (9%) had a complete response, 1 (9%) had a partial response and 9 (82%) had stable disease. We conclude that CV301 administered with PD-1 inhibitors is safe and clinically active in patients with advanced NSCLC. The frequency or severity of AEs is not increased, including irAEs for each component of the combination.
AB - CV301, a poxviral-based vaccine, has been evaluated in a phase 1 clinical trial (NCT02840994) and shown to be safe and immunologically active (phase 1a). Preclinical data support a combination of CV301 with programmed death-1 inhibitors, which has been evaluated in the phase 1b part of this trial and is reported here. Patients with advanced nonsquamous non-small cell lung cancer (NSCLC) without actionable genomic alterations received two priming doses of modified vaccinia Ankara-BN-CV301 (MVA) 4 weeks apart, followed by boosting doses of fowlpox-CV301 (FPV) at increasing time intervals for a maximum of 17 doses in combination with nivolumab for cohort 1 (C1) and 15 doses in combination with pembrolizumab for cohort 2 (C2). The primary objective was evaluation of safety and tolerability. Between October 2017 and September 14, 2018, patients were enrolled (C1: 4; median age: 64 years). Mean treatment duration was 332 days in C1 and 289 days in C2. CTCAE ≥grade 3 adverse events (AEs) were observed in four (100%) patients in C1 and three (37.5%) patients in C2. There was one death on trial. Immune-related AEs (irAEs) fulfilling criteria for a dose-limiting toxicity included 1 case of pneumonitis. Among 11 evaluable patients, 1 (9%) had a complete response, 1 (9%) had a partial response and 9 (82%) had stable disease. We conclude that CV301 administered with PD-1 inhibitors is safe and clinically active in patients with advanced NSCLC. The frequency or severity of AEs is not increased, including irAEs for each component of the combination.
KW - immunotherapy
KW - non-small cell lung cancer
KW - programmed cell death 1 receptor
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=85137663689&partnerID=8YFLogxK
U2 - 10.1002/ijc.34267
DO - 10.1002/ijc.34267
M3 - Article
C2 - 36054490
AN - SCOPUS:85137663689
SN - 0020-7136
VL - 152
SP - 447
EP - 457
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 3
ER -