BridgeBio Pharma has dosed the first participant in the Phase I/II clinical trial of BBP-398 in combination with Bristol Myers Squibb’s Opdivo (nivolumab) in non-small cell lung cancer (NSCLC) patients with KRAS mutations.

The Phase I trial has been designed for assessing the pharmacodynamics, tolerability, preliminary efficacy, pharmacokinetics, and safety of the investigational SHP2 inhibitor BBP-398 along with Opdivo. It involves two parts, Phase Ia dose escalation and Phase Ib dose expansion.

Patients with advanced NSCLC with a KRAS mutation who were not responsive to standard of care will be enrolled in both the dose escalation and expansion periods.

The dose expansion part will assess the antitumor activity of the combination of BBP-398 and Opdivo.

BridgeBio Pharma expects that the combination therapy will address the serious unmet need for patients with KRAS-mutated NSCLC as well as other advanced solid tumours with KRAS mutations, if approved.

BridgeBio Pharma oncology chief scientific officer Eli Wallace said: “SHP2 has been shown to be a key regulator of both tumour and immune cell signalling. In KRAS mutant tumours, SHP2 promotes survival, proliferation, and decreased immunogenicity by driving the active form of KRAS, while in immune cells, it associates with PD-1 which leads to immunosuppression in the tumour microenvironment.

“By partnering with Bristol Myers Squibb on this trial, we hope to show that targeting PD-1 with a two-prong approach can unlock the potent benefits of immunotherapy against this cancer and provide new treatment options for patients who need them.”

The company expects to receive the initial Phase I data from the ongoing BBP-398 trial this year.