PF-06873600 is an investigational compound developed by Pfizer. It is an inhibitor of cyclin-dependent kinases (CDK) 2, 4, and 6, not a selective androgen receptor modulator (SARM). This compound is currently undergoing clinical evaluation and has not received approval for general medical use.
Understanding its Mechanism
PF-06873600 functions as a cancer growth blocker by targeting Cyclin-Dependent Kinases 2, 4, and 6 (CDK2/4/6). These proteins stimulate cancer cells to grow and divide. By inhibiting CDK2, CDK4, and CDK6, PF-06873600 aims to inhibit the proliferation of these abnormal cells.
The rationale behind targeting CDK2 is particularly relevant when cancer cells have developed resistance to existing CDK4/6 inhibitors due to overexpression of cyclin E. This simultaneous inhibition of CDK2, CDK4, and CDK6 represents a novel therapeutic approach in oncology. The drug is administered orally as a tablet.
Targeted Conditions
PF-06873600 is being investigated for its potential in treating various types of cancer where CDK activity is implicated in disease progression. This includes hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer.
The compound is also being studied in patients with triple-negative breast cancer (TNBC), a more aggressive form lacking these hormone receptors and HER2 proteins. Additionally, it has been explored for use in advanced platinum-resistant epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.
Current Research Progress
PF-06873600 has undergone a Phase 1/2a clinical study (NCT03519178) to assess its safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity. The study involved 153 participants. It included monotherapy dose escalation and dose finding with PF-06873600 in combination with endocrine therapy.
The recommended dose for expansion (RDE) of PF-06873600 was determined to be 25 mg twice daily. Dose expansion parts further assessed preliminary antitumor activity and safety in patients with HR+/HER2- metastatic breast cancer in combination with fulvestrant. The study was terminated by Pfizer in September 2022 following a review of clinical results within their oncology portfolio.
Observed Effects and Safety Considerations
In clinical studies, PF-06873600 demonstrated preliminary clinical activity in hormone receptor-positive/HER2-negative metastatic breast cancer. Reductions in markers like Ki67-positive cells and phosphorylated Rb histo-score were observed. The study reported partial responses (PR) in some patients.
Regarding safety, the most frequently reported adverse events included nausea, anemia, and fatigue. During dose escalation, some patients experienced treatment-related dose-limiting toxicities. While the drug showed a benefit-risk profile consistent with other CDK4/6 inhibitors, its long-term safety profile remains under investigation. PF-06873600 is not approved for use outside of clinical trials, and individuals should consult healthcare professionals for any medical concerns.