Imperial drug candidate for breast cancer delivers positive Phase 2 results

A drug candidate discovered at Imperial has shown promise for treating breast cancers that have stopped responding to other therapies in a Phase 2 trial.

The encouraging trial results were announced yesterday by Carrick Therapeutics, a biopharmaceutical company that is clinically developing the candidate, named samuraciclib.

Samuraciclib is designed to treat cases of advanced HER2-negative breast cancer that are no longer responding to fulvestrant, a drug that prevents cancer cells from receiving the oestrogen that many cancers need to grow.

Samuraciclib is the latest example in an extremely exciting pipeline of potential therapies we have coming out of Imperial. Dr Mike Romanos Associate Dean for Enterprise (Medicine)

Cancers sometimes make themselves resistant to fulvestrant by upregulating CDK7, an enzyme that compensates for the low oestrogen and helps the cancer cell to duplicate.

Samuraciclib is the most advanced candidate in a potential new class of drugs that could overcome this resistance by inhibiting CDK7, a therapeutic approach first identified by researchers at Imperial.

One of the co-inventors, Professor Charles Coombes in Imperial’s Department of Surgery and Cancer, said in 2018: “Treatment-resistant tumours represent a significant threat for patients, as once a cancer stops responding to treatments there is increasingly little clinicians can do. Drugs such as these could help to shift the balance back in favour of the patients, potentially providing a new option to patients for whom existing treatments no longer work.”

The Phase 2 trial, designed to test safety and efficacy in patients, aimed to find out how well samuraciclib performs in combination with fulvestrant for breast cancers that lack the HER2 protein and depend on hormones for survival, conditions that are both met for most cases of breast cancer.

The trial was also designed to test the treatment on a specific stratum of patients within the cohort with TP53 wild type cancers, which are free from a mutation in the TP53 gene that if present can make cancers more aggressive.

It found that within this stratum, the combination of samuraciclib and fulvestrant caused the cancer to reduce substantially in size in 55% of patients and yielded a median 14.5 months progression-free survival, compared to 29% and 6.8 months with fulvestrant alone.

While future development is expected to focus on this population, a benefit was also observed in the wider cohort that included cancers with TP53 mutations. The trial also found that the drug candidate was well tolerated by patients.

Carrick now plans to pursue Phase 3 development of the drug. It will be aided by its fast track designation from the US Food and Drug Administration, which expedites the review of drugs that treat serious conditions and fulfil unmet needs.

Tim Pearson, Chief Executive Officer of Carrick Therapeutics, said: “The best-in-class PFS [progression-free survival] and ORR [overall response rate] of samuraciclib positions it to be a meaningful therapy that could transform how women with advanced breast cancer are treated following treatment with CDK4/6 inhibitors. We have achieved clinical proof of concept and look forward to advancing samuraciclib into a Phase 3 clinical trial in 2026 to build on these promising results.”

From scientific discovery to new medicines

The strategy of treating cancer by inhibiting CDK7 was devised by Professors Charles Coombes and Simak Ali in Imperial’s Department of Surgery and Cancer, who discovered that CDK7 makes some cancers resistant to hormone therapy through its effects on the oestrogen receptors.

They went on to collaborate with Professors Anthony Barrett and Matthew Fuchter in the Department of Chemistry, along with colleagues at Emory University, to identify a molecule that inhibits CDK7.

Early funding for this research came from the Engineering and Physical Sciences Research Council (EPSRC), and a major contribution of whole-project funding was from Cancer Research UK. The molecule was then licensed to Carrick Therapeutics with support from Imperial’s former technology transfer office, Imperial Innovations, and Cancer Research UK.

Samuraciclib is one of two therapies under development by Carrick Therapeutics, which has so far raised a total of over $150 million investment, and is also exploring the potential for samuraciclib to help treat prostate and pancreatic cancer.

Dr Mike Romanos, Associate Dean for Enterprise in Imperial’s Faculty of Medicine, said: “Samuraciclib is the latest example in an extremely exciting pipeline of potential therapies we have coming out of Imperial, which draw on the university’s advances in fundamental science and the strong backing of commercial experts, industrial partners and investors. There is good reason to be hope this one could turn out to be a game-changer for treating drug resistant breast cancer and other cancers.”