NEW YORK – JS InnoPharm said on Thursday that it enrolled its first patient in a Phase I trial studying JSI-1187 in patients with relapsed or refractory solid tumors containing mutations in the MAPK pathway.
The Phase I study is being conducted across four NCI-designated comprehensive cancer centers in the US.
The study will have a dose escalation portion evaluating JSI-1187 as a monotherapy in patients with solid tumors, and a dose-escalation portion evaluating JSI-1187 in combination with BRAF inhibitor dabrafenib (Novartis' Tafinlar).
The trial will also include an expansion portion evaluating the JSI-1187 and dabrafenib combination in three cohorts: BRAF V600-mutated metastatic melanoma patients who have received two prior therapies including anti-PD1 therapy with or without ipilimumab and treatment with BRAF or MEK inhibitors; BRAF V600-mutated metastatic melanoma patients who received adjuvant therapy after one prior therapy; and BRAF V600E-mutated non-small cell lung cancer or solid tumor patients who have received up to two prior therapies.
MAPK pathway mutations include mutations or gene fusions in BRAF, RAS, MEK, RAS-GAP and RAS-GEF. MAPK signaling through RAS, RAF, MEK and ERK can contribute to cancer growth and proliferation. JSI-1187 is the company's lead investigational drug candidate that inhibits the ERK1 and ERK2 enzymes.
"By utilizing an ERK inhibitor against tumors harboring mutations in the MAPK pathway, we hope to develop more effective single-agent and combination therapies by preventing the early development of resistance seen with current MAPK-targeted agents," Linda Paradiso, chief development officer for Strategia Pharmaceuticals, said in a statement. Strategia is JS InnoPharm's development partner in the US and it will manage the Phase I trial here.