US-based biopharmaceutical firm Kura Oncology has started dosing patients in its Phase I clinical trial of KO-947 for the treatment of relapsed and / or refractory, non-hematological malignancies.

KO-947 is a potent and selective, small-molecule inhibitor of extracellular-signal-regulated kinases 1 and 2 (ERK1/2).

The molecule is reported to possess anti-proliferative activity against tumour cell lines with mutations in BRAF, NRAS or KRAS and also inhibits prolonged pathway both in vitro and in vivo.

The Phase I trial will establish the maximum tolerated dose of KO-947 in subjects with locally advanced, unresectable or metastatic non-hematological malignancies.

Kura Oncology president and chief executive officer Troy Wilson said: “We are committed to the discovery and development of product candidates that target oncogenes and oncogenic pathways for the treatment of cancer.

"We are committed to the discovery and development of product candidates that target oncogenes and oncogenic pathways for the treatment of cancer."

“We believe KO-947 holds much promise as a potential therapeutic, and its advancement into the clinic underscores Kura’s productivity and commitment to building a diverse pipeline of precision medicines.”

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A dose escalation, maximum-tolerated dose expansion and one or more tumour-specific extension cohorts will also be included in the trial.

Tumour-specific cohorts for non-small-cell lung cancer with mutations in RAS or BRAF and for squamous cell carcinomas have currently been identified as potential extension cohorts.

In preclinical cell line and patient derived xenograft models such as KRAS-mutant and BRAF-mutant adenocarcinomas and squamous cell carcinomas without BRAF / RAS mutations, KO-947 was found to have significant tumour regression.

The firm is also developing a farnesyl transferase inhibitor called tipifarnib and an menin-MLL protein-protein interaction inhibitor known as KO-539.

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