SynthesisClinical cancer research : an official journal of the American Association for Cancer Research2014
Is the "3+3" dose-escalation phase I clinical trial design suitable for therapeutic cancer vaccine development? A recommendation for alternative design.
Synthesis in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand-binding Domain (pTVG-AR, MVI-118) in Patients with Metastatic Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Statistical controversies in clinical research: early-phase adaptive design for combination immunotherapies.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- A Phase I/II adaptive design to determine the optimal treatment regimen from a set of combination immunotherapies in high-risk melanoma.Contemporary clinical trials · 2015Trial
- Colorectal cancer and tumor vaccines (Review).Oncology letters · 2026Review
- Safety and immunogenicity of a tri-antigen vaccine targeting IGFBP-2, HER2, and IGF-IR in participants with non-metastatic breast cancer.Journal for immunotherapy of cancer · 2026Article
- Bright side of the dark genome: antigens for next-gen cancer vaccines.Journal for immunotherapy of cancer · 2026Review
- Cancer vaccines as enablers of immunotherapy.Nature immunology · 2025Review
- Preclinical development and clinical safety assessment of a synthetic peptide conjugate enabling endogenous antibody binding to promote innate receptor engagement.Molecular therapy. Oncology · 2025Article
- Cancer vaccine trial evaluations: immunobridging and potential immunological endpoints.Immunotherapy advances · 2025Review
- Plant-derived EpCAM-Fc fusion proteins induce in vivo immune response to produce IgGs inhibiting invasion and migration of colorectal cancer cells.Plant cell reports · 2024Article
- Advances and applications of RNA vaccines in tumor treatment.Molecular cancer · 2024Review
- Dose optimization of an adjuvanted peptide-based personalized neoantigen melanoma vaccine.PLoS computational biology · 2024Article
- The "Great Debate" at Immunotherapy Bridge 2022, Naples, November 30th-December 1st, 2022.Journal of translational medicine · 2023Article
- Breast cancer vaccines for treatment and prevention.Breast cancer research and treatment · 2022Review
- Colorectal cancer vaccines: The current scenario and future prospects.Frontiers in immunology · 2022Review
- Beyond Sequencing: Prioritizing and Delivering Neoantigens for Cancer Vaccines.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Immunization with a Plasmid DNA Vaccine Encoding the N-Terminus of Insulin-like Growth Factor Binding Protein-2 in Advanced Ovarian Cancer Leads to High-level Type I Immune Responses.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Vaccine-Based Immunotherapy for Head and Neck Cancers.Cancers · 2021Review
- Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Cytotoxic T cells isolated from healthy donors and cancer patients kill TGFβ-expressing cancer cells in a TGFβ-dependent manner.Cellular & molecular immunology · 2021Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
purposePhase I clinical trials are generally conducted to identify the maximum tolerated dose (MTD) or the biologically active dose (BAD) using a traditional dose-escalation design. This design may not be applied to cancer vaccines, given their unique mechanism of action. The FDA recently published "Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines." However, many questions about the design of cancer vaccine studies remain unanswered. EXPERIMENTAL
designWe analyzed the toxicity profile in 239 phase I therapeutic cancer vaccine trials. We addressed the ability of dose escalation to determine the MTD or the BAD in trials that used a dose-escalation design.
resultsThe rate of grade 3/4 vaccine-related systemic toxicities was 1.25 adverse events per 100 patients and 2 per 1,000 vaccines. Only two of the 127 dose-escalation trials reported vaccine-related dose limiting toxicities, both of which used bacterial vector vaccines. Out of the 116 trials analyzed for the dose-immune response relationship, we found a statistically significant dose-immune response correlation only when the immune response was measured by antibodies (P < 0.001) or delayed type hypersensitivity (P < 0.05). However, the increase in cellular immune response did not appear further sustainable with the continued increase in dose.
conclusionsOur analysis suggests that the risks of serious toxicities with therapeutic cancer vaccines are extremely low and that toxicities do not correlate with dose levels. Accordingly, the conventional dose-escalation design is not suitable for cancer vaccines with few exceptions. Here, we propose an alternative design for therapeutic cancer vaccine development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.