Immuneering announces results from Phase 1 portion of IMM-1-104 Phase 1/2a trial

Immuneering announced positive topline results from the ongoing Phase 1 portion of its Phase 1/2a clinical trial of IMM-1-104 in advanced RAS-mutant solid tumors. Topline Results from IMM-1-104 Study Phase 1 Portion: Safety and Tolerability Results: As of February 20, 2024, IMM-1-104 has been well-tolerated, with the potential for a differentiated safety profile. Among treatment-related adverse events occurring in greater than 10% of patients, no grade 4 TRAEs were observed, only one grade 3 TRAE was observed, and a modest number of grade 2 TRAEs were observed in each category. No TRAEs were deemed serious. Deep Cyclic Inhibition Proof of Concept for IMM-1-104: As of February 20, 2024 patient plasma data showed IMM-1-104 at 320mg inhibiting phosphorylated extracellular signal-regulated kinase at a level of 90% or greater for 2.7 hours, before returning to near-zero levels in advance of 24 hours. IMM-1-104 at a 240mg dose achieved 90% or greater levels of pERK inhibition for 1.9 hours, before returning to near-zero levels in advance of 24 hours. Immuneering evaluated both 240mg and 320mg QD as prospective doses for the Phase 2a portion of its Phase 1/2a study. Based on data from this trial, Immuneering selected a candidate RP2D of 320mg QD. Universal-RAS Proof of Concept for IMM-1-104: As of February 20, 2024, 100% of evaluable patients profiled by ctDNA and treated with IMM-1-104 experienced no new acquired alterations in RAS. Excluding two patients treated with IMM-1-104 at 160mg (which Immuneering believes to be a sub-therapeutic dose), no new acquired alterations in MAPK pathway genes were observed, suggesting that there was no mutation in the MAPK pathway that a tumor could use to evade IMM-1-104. Initial Signs of Clinical Activity: While clinical activity was not an endpoint of the Phase 1 portion of the trial, Immuneering believes data generated as of the cutoff date of February 20, 2024 show promising signs for IMM-1-104’s potential clinical activity: 53% of patients had greater than or equal to 1 target lesion regress when treated with IMM-1-104 at either 320mg or 240mg. Best individual lesion regressions were -35.7% at 320mg in second-line setting. Best RECIST SLD was -18.9% at 320mg in second-line setting. Longest duration on therapy was 162 days at 240mg, with no TRAEs. Immuneering plans to present further data from the ongoing Phase 1 portion of its Phase 1/2a study of IMM-1-104 in advanced RAS-mutant solid tumors at a future medical meeting. Immuneering’s Phase 1 portion of its Phase 1/2a clinical trial is an open-label study designed to evaluate the safety, tolerability, PK and preliminary efficacy of IMM-1-104 in patients with advanced RAS mutant solid tumors. The Phase 1 portion is being conducted at five clinical sites in the United States. Data from the Phase 1 portion led to Immuneering’s candidate RP2D of 320mg for IMM-1-104. The Phase 2a portion is expected to include up to twenty clinical sites and has already dosed its first patient.