Carrick Therapeutics has announced promising new clinical data for samuraciclib, its first-in-class CDK7 inhibitor, showing significant survival benefits in specific subgroups of hormone receptor positive (HR+) advanced breast cancer patients who had previously received CDK4/6 inhibitor therapy.
The findings, presented at the 2025 ESMO Breast Cancer Annual Congress in Munich, Germany, demonstrate that patients without TP53 mutations or liver metastases experienced substantially extended progression-free survival when treated with samuraciclib in combination with selective estrogen receptor degraders (SERDs).
Biomarker-Driven Patient Selection Shows Promising Results
The analysis combined data from two independent Phase 2 clinical trials: the MORPHEUS trial, which evaluated samuraciclib in combination with giredestrant, and the Module 2A trial, which tested samuraciclib with fulvestrant.
In the MORPHEUS trial, patients without TP53 mutations achieved a median progression-free survival of 14.2 months, compared to just 1.8 months for those with TP53 mutations. Similarly, in the Module 2A trial, patients without TP53 mutations reached 7.4 months of progression-free survival versus 1.8 months for those with mutations.
The absence of liver metastases also emerged as a significant predictor of treatment response. Patients without liver metastases in the MORPHEUS trial achieved 14.2 months of progression-free survival, while those in the Module 2A trial reached 13.8 months. In contrast, patients with liver metastases showed substantially shorter progression-free survival of 1.8 and 2.8 months, respectively.
"Based on the results from these two independent studies, we have identified patient populations showing improved progression-free survival, highlighting the potential of samuraciclib in combination with SERDs as an effective new treatment option for these patients," said Tim Pearson, Chief Executive Officer of Carrick Therapeutics.
Addressing an Unmet Need in HR+ Breast Cancer
HR+, HER2-negative breast cancer patients typically receive CDK4/6 inhibitors combined with endocrine therapy as standard treatment. However, resistance to these therapies inevitably develops, creating a significant unmet medical need.
Dr. Stuart McIntosh, Chief Medical Officer of Carrick Therapeutics, emphasized this challenge: "Patients with HR positive, HER2 negative advanced breast cancer are typically treated with a CDK4/6 inhibitor in combination with an endocrine therapy, but unfortunately almost all patients eventually develop resistance to therapy. Those patients are in need of effective new targeted therapies that are durable and tolerable in combination with endocrine therapy, including oral SERDs."
Mechanism of Action and Therapeutic Potential
Samuraciclib works by inhibiting CDK7, a promising therapeutic target in cancer. CDK7 regulates the transcription of cancer-causing genes, promotes uncontrolled cell cycle progression, and contributes to resistance to anti-hormone therapy.
As the most advanced CDK7 inhibitor in clinical development, samuraciclib has demonstrated a favorable safety profile and encouraging efficacy in early clinical studies. The U.S. Food and Drug Administration has granted Fast Track designation for samuraciclib in combination with fulvestrant for treating CDK4/6 inhibitor-resistant HR+, HER2- advanced breast cancer.
Beyond breast cancer, samuraciclib shows potential for treating prostate, pancreatic, small cell lung, triple negative breast, ovarian, and colorectal cancers due to its CDK7 inhibition mechanism.
Ongoing Clinical Development
Carrick Therapeutics is further validating its patient selection strategy in two ongoing Phase 2 clinical trials. The SUMIT-ELA trial, conducted in collaboration with the Menarini Group, is evaluating samuraciclib in combination with the oral SERD elacestrant. Meanwhile, the randomized SUMIT-BC trial is comparing samuraciclib plus fulvestrant versus fulvestrant alone.
Both trials focus on patients with HR+, HER2- locally advanced or metastatic breast cancer who were previously treated with a CDK4/6 inhibitor and aromatase therapy. With the completion of these multi-center international SUMIT studies, Carrick will have studied CDK7 inhibitor plus SERD combination therapy in over 150 patients.
The company plans to advance to Phase 3 trials in 2026, enriching for either patients without TP53 mutations or those without liver metastases, depending on the results of the ongoing studies expected later this year.
Broader Pipeline Development
In addition to samuraciclib, Carrick is developing CT7439, a novel CDK12/13 inhibitor and Cyclin-K glue-degrader currently in Phase 1 clinical trials. The company continues to focus on developing highly differentiated novel therapies for significant unmet needs in oncology.
Through collaborations with Roche and Menarini Group, Carrick is evaluating novel combinations of samuraciclib with oral SERD endocrine therapies, potentially expanding treatment options for patients with advanced breast cancer who have limited alternatives after developing resistance to standard therapies.
