Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2025
First-in-Human Phase I/IIa Study of the First-in-Class CDK2/4/6 Inhibitor PF-06873600 Alone or with Endocrine Therapy in Patients with Breast Cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Review of Major Advances in Breast Cancer Therapeutics in 2025: Synthesis of Conference and Published Evidence.International journal of molecular sciences · 2026Pooled it
- Next-generation CDK inhibitors in HR+/HER2- breast cancer.The Journal of clinical investigation · 2026Review
- Current and future therapies for triple-negative breast cancer.Journal of hematology & oncology · 2026Review
- WITHDRAWN: From CDK4/6 to CDK2 and KAT: Evolving therapeutic approaches in HR+/HER2- breast cancer.Breast (Edinburgh, Scotland) · 2026Article
- Beyond CDK4/6 Inhibition: Current Strategies in Hormone Receptor-Positive Metastatic Breast Cancer.Current treatment options in oncology · 2026Review
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- Frontiers in Cell-Cycle-Targeting Therapies: Addressing the Heterogeneity of the Cancer Cell Cycle.Cancers · 2026Article
- Therapeutic advances in HR+/HER2- advanced breast cancer after failure of CDK4/6 inhibitor therapy.Frontiers in oncology · 2026Review
- Targeting CDK2 for cancer therapy.Cell reports · 2025Review
- Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.Expert opinion on therapeutic targets · 2025Review
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- Cell cycle proteins: Linking the cell cycle to tumors.Oncology research · 2025Review
- Seize the engine: Emerging cell cycle targets in breast cancer.Clinical and translational medicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
Abstract
purposeThe discovery that cyclin E overexpression is a key cyclin-dependent kinase (CDK) 4/6 inhibitor resistance mechanism has reinvigorated interest in targeting CDK2 and the simultaneous inhibition of CDK2/4/6 as a novel therapeutic approach. This first-in-human study assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of PF-06873600, the first-in-class inhibitor of CDK2/4/6. PATIENTS AND
methodsDose escalation included 78 patients with advanced breast cancer, triple-negative breast cancer, or ovarian cancer who received oral PF-06873600 at doses ranging from 1 to 50 mg twice daily (part 1A, n = 51) or PF-06873600 with endocrine therapy (part 1B, n = 16; part 1C, n = 11) to determine the recommended dose for expansion (RDE). Dose expansion (part 2A, n = 45; part 2C, n = 28) assessed preliminary antitumor activity, safety, and tolerability at the RDE in combination with fulvestrant in patients with hormone receptor+/HER2- metastatic breast cancer. Pharmacodynamics and translational readouts were assessed by measuring phosphorylated Rb and Ki67 in tumor biopsies and ctDNA.
resultsThe RDE of PF-06873600 was 25 mg twice daily. During dose escalation, 6 of 42 (14.3%) evaluable patients had treatment-related dose-limiting toxicities. The most common all-causality adverse events (N = 151) were nausea (62.9%), anemia (44.4%), and fatigue (43.7%). Reductions in Ki67-positive cells, phosphorylated Rb histo-score, and ctDNA levels were observed. Three RECIST partial responses (PR) were observed in part 1. In part 2A, there were three PRs (objective response rate, 6.7%; 95% confidence interval, 1.4%-18.3%), and in part 2C, there were five PRs (objective response rate, 22.7%; 95% confidence interval, 7.8%-45.4%).
conclusionsPF-06873600 demonstrated a benefit-risk profile consistent with the CDK4/6 inhibitor class of drugs, with preliminary clinical activity in hormone receptor+/HER2- metastatic breast cancer.
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