The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to Immuneering Corporation's lead clinical-stage program, IMM-1-104, for the treatment of patients with unresectable or metastatic NRAS-mutant melanoma who have progressed on or are intolerant to PD-1/PD-L1 based immune checkpoint inhibitors. This designation aims to expedite the development and review of IMM-1-104, addressing a significant unmet need in melanoma treatment. IMM-1-104 is currently being evaluated in a Phase 2a clinical trial in patients with advanced solid tumors, including melanoma.
Clinical Significance and Tolerability
According to Ben Zeskind, Ph.D., Co-Founder and CEO of Immuneering, immune checkpoint inhibitors are vital in melanoma treatment, but options are limited for patients who progress on or are intolerant to them. Targeted therapies, including MEK and RAF inhibitors, have shown promise but are often limited by toxicity. Data presented at the European Society for Medical Oncology (ESMO) 2024 congress indicated that IMM-1-104, a novel MEK inhibitor, demonstrated unique tolerability in Phase 1 trials compared to existing MEK inhibitors used in melanoma treatment.
Fast Track Designation Benefits
Fast Track designation is designed to facilitate the development and expedite the review of medicines that treat serious conditions and fulfill unmet medical needs. It allows for more frequent interactions with the FDA to discuss the development plan and potential eligibility for accelerated approval and priority review.
IMM-1-104: A Novel MEK Inhibitor
IMM-1-104 aims to achieve universal-RAS activity, selectively impacting cancer cells more than healthy cells through Deep Cyclic Inhibition of the MAPK pathway with once-daily dosing. The ongoing Phase 2a trial (NCT05585320) is evaluating IMM-1-104 in patients with advanced solid tumors harboring RAS mutations.
Previous Clinical Data
Phase 1 results, published in Annals of Oncology, showed that IMM-1-104 disrupted the MAPK-pathway of tumors and was well-tolerated, demonstrating lesion and molecular level responses as a monotherapy. The study enrolled 45 patients, including 30 with pancreatic ductal adenocarcinoma (PDAC), and evaluated IMM-1-104 at 240 mg and 320 mg doses administered orally once per day. Early signs of clinical activity were promising, with approximately 66% of patients showing RECIST SLD below 20% and 25% having SLD 0% or below. Reductions in mean ctDNA were observed in 33% of patients.
Ongoing Clinical Trial
The Phase 2a portion of the trial is evaluating patients with locally advanced or metastatic solid tumor malignancies, including pancreatic ductal adenocarcinoma (PDAC), RAS-mutant melanoma, and RAS-mutant non-small cell lung cancer (NSCLC). IMM-1-104 is being studied alone, in combination with modified gemcitabine and nab-paclitaxel, or in combination with folfirinox.
Addressing Unmet Needs
The FDA’s Fast Track designation for IMM-1-104 in advanced melanoma underscores the urgent need for new treatment options for patients who have progressed on or are intolerant to immune checkpoint inhibitors. This designation, along with previous Fast Track designations for first and second-line pancreatic cancer, highlights the potential of IMM-1-104 across multiple cancer indications.
