Immuneering Corporation's IMM-1-104, a novel MEK inhibitor, is demonstrating promising results in an ongoing Phase 2a clinical trial for advanced pancreatic cancer. The drug, designed to improve tolerability and efficacy in RAS-mutated tumors, is being evaluated in combination with standard chemotherapy regimens and as a monotherapy.
Combination Therapies Show Encouraging Results
Data from the Phase 2a trial indicate that IMM-1-104, when combined with modified gemcitabine/nab-paclitaxel (mGnP) in first-line pancreatic cancer patients, achieved an overall response rate (ORR) of 43% and a disease control rate (DCR) of 86% as of December 5, 2024. These results compare favorably to the benchmark ORR of 23% and DCR of 48% observed with gemcitabine/nab-paclitaxel alone in the Phase 3 MPACT study. According to Dr. Tanios Bekaii-Saab from the Mayo Clinic Cancer Center, the combination of IMM-1-104 with mGnP may provide improved efficacy and tolerability versus mGnP alone.
Furthermore, initial data from a separate Phase 2a arm evaluating IMM-1-104 with modified FOLFIRINOX (mFFX) in first-line pancreatic cancer patients showed target tumor shrinkage in all evaluable patients (n=4), with one patient experiencing a complete 100% reduction in target lesions. The combination was generally well-tolerated.
Monotherapy Shows Potential in Second-Line Treatment
In second-line pancreatic cancer patients treated with IMM-1-104 monotherapy, 11 out of 21 evaluable patients achieved disease control, with one patient experiencing a 67% reduction in target lesions. This data suggests that IMM-1-104 may be suitable for both monotherapy and combination therapy approaches.
Expansion of Clinical Development
Immuneering plans to expand the Phase 2a trial in 2025, adding three new combination arms. These will investigate IMM-1-104 in combination with a BRAF inhibitor for BRAF-mutant melanoma, and with immune checkpoint inhibitors for both melanoma and non-small cell lung cancer (NSCLC). These expansions aim to explore the full therapeutic potential of IMM-1-104 across various cancer types.
Regulatory Status and Financial Position
IMM-1-104 has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of first- and second-line pancreatic cancer, as well as for unresectable or metastatic NRAS-mutant melanoma. Immuneering has also successfully raised net proceeds of $13.7 million through its at-the-market equity offering program as of January 2025, which is expected to support ongoing research and development activities.
Safety and Tolerability
IMM-1-104 has demonstrated a differentiated tolerability profile in clinical trials. The treatment is expected to be better tolerated than current MEK inhibitors, potentially leading to improved patient outcomes and compliance. In the monotherapy arm of the Phase 2a trial, no Grade 3 or Grade 4 treatment-related adverse events were observed, and only a handful of Grade 2 events were reported.
Future Directions
With further updates from the IMM-1-104 Phase 2a trials expected in the second quarter of 2025, Immuneering is positioning IMM-1-104 for future pivotal clinical trials. The company's continued progress is eagerly awaited, as it could bring much-needed innovation to the treatment of pancreatic cancer and other difficult-to-treat cancers.
