BeiGene's RAF dimer inhibitor, lifirafenib (BGB-283), will be evaluated in combination with SpringWorks Therapeutics’ investigational MEK inhibitor, PD-0325901, in a phase 1b clinical trial in patients with advanced solid tumors.
In this regard, the two firms have signed a global clinical collaboration agreement to assess the safety, tolerability and preliminary efficacy of their drugs combination.
Lifirafenib is a small molecule kinase inhibitor having RAF monomer and dimer inhibition activities.
BeiGene said the inhibitor demonstrated antitumor activities in preclinical models and in cancer patients with tumors harboring BRAF V600E mutations, non-V600E BRAF mutations and also non-small cell lung cancer and endometrial cancer harboring KRAS mutations.
On the other hand, PD-0325901, which inhibits MEK, has been demonstrated in clinical biopsies to block MEK phosphorylation. Due to this action, it can arrest cellular growth and lead to cell death.
BeiGene and SpringWorks believe that by vertically inhibiting the MAPK pathway, the combination approach of lifirafenib and PD-0325901 could surpass feedback loops that have hampered therapeutic development for RAS-mutant solid tumors.
As per the terms of their collaboration, BeiGene will take up responsibility for administering the early-stage trial which is likely to begin during the first quarter of 2019.
The phase 1b will enroll patients with advanced solid tumors that promote RAS, RAF mutations and other MAPK pathway aberrations.
SpringWorks Therapeutics CEO Saqib Islam said: “Mutations in RAS genes are found in roughly one-fourth of all human cancers, making this a critically important area for developing new cancer treatments. Despite decades of research, no anti-RAS therapies have been approved to date.
“The combination of a MEK inhibitor with a RAF dimer inhibitor has strong scientific rationale, and we look forward to partnering with BeiGene to build upon the existing preclinical data, which have demonstrated potential benefits with this combination therapy approach.”
As per the terms of the agreement, all costs of the clinical studies and governance responsibilities will be equally shared by the partners. SpringWorks will also monitor fixed-dose formulation work.
BeiGene co-founder, CEO and chairman John Oyler said: “BeiGene is committed to developing innovative medicines for cancer patients with little or no treatment options.
“We are delighted to work with SpringWorks Therapeutics to explore the potential benefits of this combination in patients with RAS mutations, a patient population with high unmet medical needs.”