ArticleJournal for immunotherapy of cancer2018
Design considerations for early-phase clinical trials of immune-oncology agents.
Article in Journal for immunotherapy of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Pooled it
- Surv-CRM-12: A Bayesian phase I/II survival CRM for right-censored toxicity endpoints with competing disease progression.Statistics in medicine · 2022Trial
- PRO-ADD: Patient-empowered dose-finding trials integrating safety, preliminary efficacy and patient-reported outcomes for optimal dose selection.Statistical methods in medical research · 2026Article
- Kidney-Tonifying, Phlegm-Resolving, and Blood Stasis-Removing Therapy for Multiple Myeloma: Protocol for a Randomized Controlled Trial on Epigenetic and Immune Modulation.JMIR research protocols · 2026Article
- Immune-related adverse events occurring rapidly after a single dose of immune checkpoint blockade.Journal for immunotherapy of cancer · 2025Article
- A model-free phase I/II dose optimization design for immunotherapy trials.Statistical methods in medical research · 2025Article
- Ten challenges and opportunities in computational immuno-oncology.Journal for immunotherapy of cancer · 2024Review
- Adaptive Bayesian information borrowing methods for finding and optimizing subgroup-specific doses.Clinical trials (London, England) · 2024Review
- An overview of statistical methods for biomarkers relevant to early clinical development of cancer immunotherapies.Frontiers in immunology · 2024Review
- Local continual reassessment methods for dose finding and optimization in drug-combination trials.Statistical methods in medical research · 2023Article
- Recent advances and clinical pharmacology aspects of Chimeric Antigen Receptor (CAR) T-cellular therapy development.Clinical and translational science · 2022Review
- Optimizing the future: how mathematical models inform treatment schedules for cancer.Trends in cancer · 2022Review
- Recruitment, outcomes, and toxicity trends in phase I oncology trials: Six-year experience in a large institution.Cancer reports (Hoboken, N.J.) · 2022Article
- Healthy volunteers in first-in-human oncology drug development for small molecules.British journal of clinical pharmacology · 2022Review
- Concentration optimization of combinatorial drugs using Markov chain-based models.BMC bioinformatics · 2021Article
- Seamless phase I/II design for novel anticancer agents with competing disease progression.Statistics in medicine · 2021Article
- Which factors matter the most? Revisiting and dissecting antibody therapeutic doses.Drug discovery today · 2021Review
- Quantifying the limits of CAR T-cell delivery in mice and men.Journal of the Royal Society, Interface · 2021Article
- Immune Biology of Acute Myeloid Leukemia: Implications for Immunotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Review
- Considerations when treating high-grade pediatric glioma patients with immunotherapy.Expert review of neurotherapeutics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWith numerous and fast approvals of different agents including immune checkpoint inhibitors, monoclonal antibodies, or chimeric antigen receptor (CAR) T-cell therapy, immunotherapy is now an established form of cancer treatment. These agents have demonstrated impressive clinical activity across many tumor types, but also revealed different toxicity profiles and mechanisms of action. The classic assumptions imposed by cytotoxic agents may no longer be applicable, requiring new strategies for dose selection and trial design. DESCRIPTION: This main goal of this article is to summarize and highlight main challenges of early-phase study design of immunotherapies from a statistical perspective. We compared the underlying toxicity and efficacy assumptions of cytotoxic versus immune-oncology agents, proposed novel endpoints to be included in the dose-selection process, and reviewed design considerations to be considered for early-phase trials. When available, references to software and/or web-based applications were also provided to ease the implementation. Throughout the paper, concrete examples from completed (pembrolizumab, nivolumab) or ongoing trials were used to motivate the main ideas including recommendation of alternative designs.
conclusionFurther advances in the effectiveness of cancer immunotherapies will require new approaches that include redefining the optimal dose to be carried forward in later phases, incorporating additional endpoints in the dose selection process (PK, PD, immune-based biomarkers), developing personalized biomarker profiles, or testing drug combination therapies to improve efficacy and reduce toxicity.
Indexed as
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What OpenQuestion holds
Registered trials
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.