A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer
Open accessAbstract
Background Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-β2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment.Methods Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival.Results This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p=0.594). There were also no differences in progression-free survival (4.3months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p=0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p=0.002) and that prior radiation was a positive prognostic factor (median survival 28.4months with belagenpumatucel-L versus 16.0months with placebo; HR 0.61, p=0.032).Conclusions Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted.
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TGF-β blockade using the TβRI kinase inhibitor SM16 enhanced the antitumor effects of an immune-activating adenoviral vector encoding IFN-β and an adenoviral HPV E7 vaccine therapy in mesothelioma and lung cancer models.
“TGF-β blockade using a TβRI kinase inhibitor, SM16, enhanced the antitumor effects of an immune-activating adenoviral vector encoding IFN-β, and an adenoviral HPV E7 vaccine therapy in models of mesothelioma and lung cancer372.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [372]
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- Authors
- Giaccone, G., Bazhenova, L. A., Nemunaitis, J., Tan, M., Juhász, E., Ramlau, R., van den Heuvel, M. M., Lal, R., Kloecker, G. H., Eaton, K. D., Chu, Q., Dunlop, D. J., Jain, M., Garon, E. B., Davis, C. S., Carrier, E., Moses, S. C., Shawler, D. L., & Fakhrai, H.
- Affiliations
- National Institutes of Health (US)
- University of California San Diego (US)
- Mary Crowley Cancer Research Center (US)
- Georgetown University (US)
- Országos Korányi Tbc és Pulmonológiai Intézet (HU)
- Poznan University of Medical Sciences (PL)
- Guy's Hospital (GB)
- University of Louisville (US)
- Seattle Cancer Care Alliance (US)
- Cross Cancer Institute (CA)
- Glasgow Royal Infirmary (GB)
- Noble Hospital (IN)
- University of California, Los Angeles (US)
- NovaRx (United States) (US)
- Corresponding author
- Giaccone, G.
- ORCID
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 51
- Issue
- 16
- Pages
- 2321-2329
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W1702502468
- Cited by
- 279
- References
- 40
- Citations by year
- 2026: 12 · 2025: 23 · 2024: 27 · 2023: 16 · 2022: 28 · 2021: 28 · 2020: 27 · 2019: 22 · 2018: 21 · 2017: 26 · 2016: 31 · 2015: 7 · 2014: 8
- FWCI
- 22.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- European Journal of Cancer (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- SBIR (R44 CA096025)
- NovaRx Corporation
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- therapeutic cancer vaccines, non-small cell lung cancer, maintenance therapy, platinum-based chemotherapy, overall survival, progression-free survival, prognostic factors, prior radiotherapy
- MeSH terms
- Adult, Aged, Carcinoma, Non-Small-Cell Lung, Double-Blind Method, Female, Humans, Lung Neoplasms, Male, Middle Aged, Time Factors, Proportional Hazards Models, Treatment Outcome, Disease Progression, Disease-Free Survival, Cancer Vaccines, Kaplan-Meier Estimate, Intention to Treat Analysis, Maintenance Chemotherapy
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