Samuraciclib Therapy Combo Shows Responses in HR+ Advanced Breast Cancer

Patients without TP53 mutations or liver metastases saw longer progression-free survival with samuraciclib combos after CDK4/6 inhibitor therapy.

Results from two phase 2 trials support treatment with the novel, first-in-class inhibitor samuraciclib for the treatment of patients with hormone receptor positive (HR)–positive advanced breast cancer following prior CDK4/6 inhibitor therapy, according to a news release from Carrick Therapeutics Inc.

The phase 2 MORPHEUS and Module 2A trials evaluated samuraciclib treatment in combination with giredestrant, as well as in combination with fulvestrant, respectively. The results from these two independent clinical trials were shared in a poster presentation at the 2025 ESMO Breast Cancer Annual Congress held in Munich, Germany.

The MORPHEUS and Module 2A trials demonstrated extended progression-free survival in people without TP53 mutations or without liver metastases, according to the news release.

“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 [selective estrogen receptor degraders (SERDs)] as an effective new treatment option for these patients. Carrick is further validating these two selection strategies in two additional phase 2 studies reading out later this year with the intent to advance to phase 3 in 2026, enriching for one of these two patient groups,” said Tim Pearson, CEO of Carrick Therapeutics.

Breaking Down the Findings

The MORPHEUS trial evaluated 15 patients who received combination treatment with samuraciclib and giredestrant. Patients without a TP53 mutation achieved a median progression-free survival (PFS) of 14.2 months. In contrast, those with a TP53 mutation had a median PFS of 1.8 months. Similarly, patients without liver metastases experienced a median PFS of 14.2 months, whereas those with liver metastases had a median PFS of 1.8 months.

In the Module 2A trial, which evaluated 31 patients, investigators studied samuraciclib in combination with fulvestrant. The median PFS was 7.4 months in patients without a TP53 mutation and 1.8 months in those with the mutation. Among patients without liver metastases, the median PFS was 13.8 months, compared with 2.8 months in those with liver metastases.

These data demonstrated longer PFS in patients without a TP53 mutation versus with those who had a mutation, as well as in patients without liver metastases compared with those who had liver involvement. Therefore, these findings further validate a biomarker-driven patient selection.

“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,” said Dr. Stuart McIntosh, chief medical officer of Carrick Therapeutics, in the news release. “Those patients are in need of effective new targeted therapies that are durable and tolerable in combination with endocrine therapy, including oral SERDs. These results from two independent trials of samuraciclib in combination with a SERD are very encouraging.”

Samuraciclib is the most clinically advanced cyclin-dependent kinase 7 (CDK7) inhibitor currently in clinical development, according to the news release. Targeting CDK7 is an often-used strategy in oncology, as it plays a key role in driving the transcription of cancer-causing genes, facilitating uncontrolled cell cycle progression and contributing to resistance against anti-hormone therapies.

As an oral CDK7 inhibitor, the agent has shown a favorable safety profile and encouraging early efficacy in patients with HR-positive breast cancer. Due to its mechanism of action, samuraciclib is also expected to benefit in the treatment of patients with prostate, pancreatic, small cell lung, triple-negative breast, ovarian and colorectal cancers.

Notably, the news release shares that the United States Food and Drug Administration (FDA) has granted fast track designation to samuraciclib in combination with fulvestrant for the treatment of CDK4/6 inhibitor–resistant HR-positive, HER2-negative advanced breast cancer.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.