Deciphera Pharmaceuticals has begun Phase Ib/II trial assessing rebastinib in combination with carboplatin for the treatment of patients with advanced or metastatic solid tumours.

The open-label, multicentre trial will be conducted in two parts.

Part I will investigate the safety, tolerability and pharmacokinetics of twice-daily dose of 50mg and 100mg rebastinib in combination with carboplatin.

This part is also designed to identify the recommended Phase II dose (RP2D) of rebastinib and carboplatin combination in patients with advanced or metastatic solid tumours that are refractory to standard therapies.

“The biological mechanisms by which tumours co-opt the surrounding microenvironment to grow are becoming better understood.”

In Part II of the trial, Deciphera is expected to examine the safety, tolerability, and efficacy of the RP2D of the study drug combination once every three weeks.

This part will include several cohorts of patients, including breast cancer, ovarian cancer, and mesothelioma.

Around 18 patients and up to 99 patients are expected to be enrolled in the trial’s part I and II portions respectively.

Deciphera Pharmaceuticals chief scientific officer Daniel Flynn said: “The biological mechanisms by which tumours co-opt the surrounding microenvironment to grow, survive and become more invasive, are becoming better understood.

“Recent research indicates that TIE2 kinase is involved in multiple mechanisms favouring a pro-tumoural microenvironment, including the regulation of a population of immunosuppressive macrophages, promotion of tumour angiogenesis, and function of perivascular pumps that lead to tumour cell recruitment and metastasis.

“In addition, use of chemotherapeutic agents are believed to enhance the recruitment of these macrophages, leading to increased tumour vascularization and dissemination.”

Deciphera’s rebastinib is an investigational orally administered, small molecule switch control inhibitor of TIE2 kinase.