Senhwa Biosciences has enrolled its first patient in a multicentre phase I/II clinical trial to study its investigational product CX-5461 in triple-negative breast cancer (TNBC) patients with BRCA1/2 mutation or Homologous Recombination Defect (HRD).

The clinical trial will study the use of a small molecule G-quadruplex stabiliser known as CX-5461 to selectively kill tumours defective in the BRCA1/2 or HR related genes through synthetic lethality concept.

BRCA1/2 mutations or HRD accounts for around 50% of the TNBC population.

TNBC is the most aggressive of all breast cancers and currently has only limited treatment options.

"TNBC is the most aggressive of all breast cancers and currently has only limited treatment options."

Senhwa biosciences senior medical officer John Soong said: "There is a high unmet medical need in this setting that must be filled.

"Positive results in this indication may propel the development of CX-5461 in additional solid tumour indications, such as ovary, lung, pancreas, prostate, and gastrointestinal (GI) tract cancers."

The study is being sponsored by Canadian Cancer Trials Group (CCTG) and will be conducted with the support of the Ontario Institute for Cancer Research through funding provided by the Government of Ontario.

SU2C Canada-Canadian Breast Cancer Foundation Breast Cancer Dream Team-affiliated doctors and scientists from the BC Cancer Agency, Ottawa Hospital Research Institute, and University Health Network in Toronto are also taking part in the study.

Initially, the multicentre phase I/II trial will evaluate the safety and tolerability of increasing doses of CX-5461, following which a Simon 2-stage study will be taken to assess antitumour activity in TNBC patients with BRCA1/2 mutations or HRD.

The evaluation of the Objective Response Rate (ORR) is the primary endpoint, while secondary endpoints including Progression Free Survival (PFS), will be assessed using RECIST criteria.

In the phase 1 clinical trial, CX-5461 was administered to 14 patients with advanced haematologic malignancies.

CX-5461 was found to be well tolerated, with low grade manageable adverse events to date.

CX-5461 is a potent G-quadruplex stabiliser that triggers replication and transcription associated DNA damage in cancer cells with defective DNA damage repair due to BRCA1/2 mutation or HR deficiency.

Normal cells have all of their DNA repair mechanisms intact, thereby allowing them to survive. By stabilising G-quadruplex, CX-5461 selectively kills tumours through the concept of synthetic lethality.