Positive Phase 1 Results for IMM-1-104 in RAS-Mutant Solid Tumors Trial

On March 14, 2024, Immuneering Corporation, a clinical-stage oncology firm, announced significant top-line outcomes from the ongoing Phase 1 segment of its Phase 1/2a clinical trial of IMM-1-104 in patients with advanced RAS-mutant solid tumors.

Ben Zeskind, CEO of Immuneering, stated that Immuneering was founded with the mission to create treatments for a broad range of cancer patients. The design of IMM-1-104 aimed to challenge traditional views by not continuously targeting and inhibiting the MAPK pathway, potentially reducing the severe toxicities usually associated with cancer treatments. Instead, Deep Cyclic Inhibition, a strategy developed from their platform insights, was used to enhance tolerability and efficacy across various RAS mutations. IMM-1-104 has shown promising results in shrinking highly aggressive, MAPK-dependent lesions, preventing new RAS alterations, and demonstrating a favorable safety profile.

Zeskind noted that the goals of Phase 1 included determining the safety and tolerance of IMM-1-104, establishing a recommended Phase 2 dose (RP2D), and assessing pharmacokinetics (PK). By the cut-off date on February 20, 2024, it was observed that patients in Phase 1 had diverse RAS mutations across multiple cancer types, with a high percentage demonstrating no prior response to metastatic disease treatments. More than two-thirds received IMM-1-104 in later treatment lines and it was well tolerated with encouraging early signs of clinical activity. These findings are promising for the ongoing Phase 2a part, which is already enrolling patients with earlier-stage mutations in order to study IMM-1-104 as both a single agent and in combination therapies.

Dr. Vincent Chung from the City of Hope commented on the encouraging initial tumor activity observed in the refractory patient population, noting the safety profile of IMM-1-104. The City of Hope looks forward to continuing its evaluation of the drug in the Phase 2a portion of the study.

As of February 20, 2024, safety data indicated that IMM-1-104 was well-tolerated. No severe (grade 4) treatment-related adverse events were recorded, and only one non-serious grade 3 event was observed. The Phase 1 trial's results validated the concept of Deep Cyclic Inhibition, showing that IMM-1-104 achieved significant inhibition of the pERK level, a critical component in the MAPK pathway, without inducing new mutations.

Clinical activity was not a primary endpoint in Phase 1, but initial signs of effectiveness were nonetheless observed: over half the patients had tumor regression, particularly those treated with 320mg and 240mg doses. Notably, the longest therapy duration without adverse events was recorded at 162 days with a 240mg dose.

Brett Hall, Ph.D., Chief Scientific Officer of Immuneering, noted that the results were consistent with prior preclinical observations. Moving forward, the company is eager to continue the Phase 2a trial with a broadened base of clinical sites and anticipates presenting further Phase 1 data at an upcoming medical conference. The promising data from Phase 1 has already established a candidate RP2D of 320mg for further studies.