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 - 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 -