PMID- 36054490
OWN - NLM
STAT- MEDLINE
DCOM- 20221220
LR  - 20231205
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 152
IP  - 3
DP  - 2023 Feb 1
TI  - Phase 1 trial of CV301 in combination with anti-PD-1 therapy in nonsquamous 
      non-small cell lung cancer.
PG  - 447-457
LID - 10.1002/ijc.34267 [doi]
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.
CI  - (c) 2022 UICC. This article has been contributed to by U.S. Government employees 
      and their work is in the public domain in the USA.
FAU - Rajan, Arun
AU  - Rajan A
AUID- ORCID: 0000-0003-2776-3385
AD  - Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, 
      National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 
      USA.
FAU - Gray, Jhanelle E
AU  - Gray JE
AD  - Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida, USA.
FAU - Devarakonda, Siddhartha
AU  - Devarakonda S
AD  - Medical Oncology, Washington University School of Medicine, St. Louis, Missouri, 
      USA.
FAU - Birhiray, Ruemu
AU  - Birhiray R
AD  - Medical Oncology, Investigative Clinical Research of Indiana, Indianapolis, 
      Indiana, USA.
FAU - Korchin, Borys
AU  - Korchin B
AD  - Bavarian Nordic, Morrisville, North Carolina, USA.
FAU - Menius, Erika
AU  - Menius E
AD  - Bavarian Nordic, Morrisville, North Carolina, USA.
FAU - Donahue, Renee N
AU  - Donahue RN
AD  - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National 
      Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
FAU - Schlom, Jeffrey
AU  - Schlom J
AD  - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National 
      Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
FAU - Gulley, James L
AU  - Gulley JL
AUID- ORCID: 0000-0002-6569-2912
AD  - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National 
      Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
AD  - Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer 
      Institute, National Institutes of Health, Bethesda, Maryland, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02840994
GR  - ZIA BC011905/ImNIH/Intramural NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220909
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 31YO63LBSN (Nivolumab)
SB  - IM
MH  - Humans
MH  - Middle Aged
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/metabolism
MH  - Drug Therapy, Combination/adverse effects
MH  - *Lung Neoplasms/drug therapy/metabolism
MH  - Nivolumab/therapeutic use
PMC - PMC10690498
MID - NIHMS1941692
OTO - NOTNLM
OT  - immunotherapy
OT  - non-small cell lung cancer
OT  - programmed cell death 1 receptor
OT  - vaccine
COIS- CONFLICT OF INTEREST Arun Rajan-None, other than the CRADA mentioned in the 
      Funding section. 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. Siddhartha Devarakonda-Dr. Devarakonda 
      has nothing to disclose. Ruemu Birhiray-Dr. Birhiray reports grants from Bavarian 
      Nordic during the conduct of the trial and personal fees or grants from 
      Pharmacyclics (an AbbVie Company), Janssen, Morphosys, ER Squibb & Sons, Incyte 
      Corporation, Glaxo Oncology, Puma Biotechnology, Amgen, AbbVie, Sanofi, Genzyme 
      Corporation, Dova/Sobi Pharmaceuticals, Exelixis, AstraZeneca Pharmaceuticals, 
      CTI, Takeda, Daiichi Sankyo, Regeneron, Lilly, Array Biopharma, Seagen, Blue 
      Medicines, Epizyme and TG Therapeutics outside the submitted work. Borys 
      Korchin-Dr. Korchin reports other (Bavarian Nordic employee) from Bavarian 
      Nordic, Morrisville, NC, USA, outside the submitted work. Erika Menius-Ms. Menius 
      reports other (Bavarian Nordic employee) from Bavarian Nordic, Morrisville, NC, 
      USA, outside the submitted work. Renee N. Donahue-None, other than the CRADA 
      mentioned in the Funding section. Jeffrey Schlom-None, other than the CRADA 
      mentioned in the Funding section. James L. Gulley-None, other than the CRADA 
      mentioned in the Funding section.
EDAT- 2022/09/03 06:00
MHDA- 2022/12/17 06:00
PMCR- 2023/12/01
CRDT- 2022/09/02 14:22
PHST- 2022/05/31 00:00 [revised]
PHST- 2022/01/14 00:00 [received]
PHST- 2022/06/28 00:00 [accepted]
PHST- 2022/09/03 06:00 [pubmed]
PHST- 2022/12/17 06:00 [medline]
PHST- 2022/09/02 14:22 [entrez]
PHST- 2023/12/01 00:00 [pmc-release]
AID - 10.1002/ijc.34267 [doi]
PST - ppublish
SO  - Int J Cancer. 2023 Feb 1;152(3):447-457. doi: 10.1002/ijc.34267. Epub 2022 Sep 9.