ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: A Phase I Dose Escalation and Expansion Study.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 81 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Immune checkpoint inhibitors in pancreatic adenocarcinoma: a systematic review and meta analysis of clinical outcomes.Frontiers in oncology · 2025Pooled it
- Review
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Review
- The tumor microenvironment in pancreatic cancer: from composition to therapeutic targeting.Biochemical Society transactions · 2026Review
- Synthesis, molecular modelling and evaluation of (-)-isopulegol-based 2,4-diaminopyrimidines as promising aurora kinase inhibitors.RSC medicinal chemistry · 2026Article
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- Emerging Precision Therapeutic Strategies in Pancreatic Ductal Adenocarcinoma: KRAS Targeting, DDR Vulnerabilities, Immune Redirection, and Tumor Microenvironment Remodeling.Pharmaceutics · 2026Review
- Review
- Mechanobiology of the tumor microenvironment: a review of therapeutic interactions and in vitro elasticity measurement techniques.Journal of biomedical science · 2026Review
- The circadian gene Dec2 promotes pancreatic cancer progression and dormancy through immune evasion.Developmental cell · 2026Article
- Current advances in immunotherapy for KRAS-Mutant pancreatic cancer.Clinical and experimental medicine · 2026Review
- Cancer-associated fibroblast targeting therapies as a tool to enhance responses to radiotherapy and immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Review
- The mechanisms and clinical prospects of combining chemotherapy with immunotherapy for advanced pancreatic cancer.Discover oncology · 2026Review
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- Single-stranded DNA in the bone microenvironment promotes prostate cancer bone metastasis via the ITGA6-FAK pathway.Communications biology · 2026Article
- Natural Isothiocyanates Block Adhesion and Invasion of Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines.Molecules (Basel, Switzerland) · 2026Article
- Article
- Anoikis: To Die or Not to Die?International journal of molecular sciences · 2026Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
24 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTargeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile. PATIENTS AND
methodsWe conducted a multicenter, open-label, phase I study with dose escalation and expansion phases. In dose escalation, patients with refractory solid tumors were treated at five escalating dose levels of defactinib and gemcitabine to identify a recommended phase II dose (RP2D). In expansion phase, patients with metastatic PDAC who progressed on frontline treatment (refractory cohort) or had stable disease (SD) after at least 4 months of standard gemcitabine/nab-paclitaxel (maintenance cohort) were treated at RP2D. Pre- and posttreatment tumor biopsies were performed to evaluate tumor immunity.
resultsThe triple drug combination was well-tolerated, with no dose-limiting toxicities. Among 20 treated patients with refractory PDAC, the disease control rate (DCR) was 80%, with one partial response (PR) and 15 SDs, and the median progression-free survival (PFS) and overall survival (OS) were 3.6 and 7.8 months, respectively. Among 10 evaluable patients in the maintenance cohort, DCR was 70% with one PR and six SDs. Three patients with SD came off study due to treatment- or disease-related complications. The median PFS and OS on study treatment were 5.0 and 8.3 months, respectively.
conclusionsThe combination of defactinib, pembrolizumab, and gemcitabine was well-tolerated and safe, had promising preliminary efficacy, and showed biomarker activity in infiltrative T lymphocytes. Efficacy of this strategy may require incorporation of more potent chemotherapy in future studies.
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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.