IMM-1-104 and Chemo Combination Elicit Responses in First-Line Pancreatic Cancer

IMM-1-104 in combination with modified gemcitabine and nab-paclitaxel (Abraxane) in the first-line setting elicited responses (in the treatment of patients with pancreatic cancer, according to data from the ongoing phase 2a portion of a phase 1/2a clinical trial (NCT05585320) shared in a news release from Immuneering.

Of the 5 patients treated in the pancreatic cancer cohort, IMM-1-104 elicited an overall response rate (ORR) of 40% and a disease control rate (DCR) of 80%; treatment was ongoing in all 5 patients continuing treatment at 240 mg of IMM-1-104 once daily, which was the study’s safety lead-in dose. Responses included 1 complete response (CR) and 1 partial response.

Furthermore, the news release noted that these early findings were consistent with preclinical data presented at the 2024 AACR Annual Meeting, which demonstrated a deeper response when these agents were combined compared with each agent alone.

“We are delighted to share today’s initial data on IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel. While the initial ORR of 40% and DCR of 80% are very encouraging—and both more than would be expected for gemcitabine/nab-paclitaxel alone—we are still in the early stages of this trial, with more scans for all 5 of these initial patients and for additional patients planned to come,” Ben Zeskind, PhD, co-founder and chief executive officer of Immuneering, stated in the news release. “Nevertheless, it was encouraging to see a CR in the first [patient with] pancreatic cancer [who was] treated with IMM-1-104 in this combination, with the patient now on treatment for over 6 months.”

IMM-1-104 is designed to achieve universal RAS inhibition to selectively target cancer cells over healthy cells via deep cyclic inhibition of the MAPK pathway. It is being investigated in patients with advanced solid tumors harboring RAS mutations in the phase 1/2a trial.

Notably, IMM-1-104 previously received fast track designation from the FDA for the treatment of first- and second-line pancreatic ductal adenocarcinoma.²

“There is a high unmet need in pancreatic cancer for novel therapies that meaningfully improve outcomes. With current therapies in pancreatic cancer, we rarely see CRs, and as such any treatment that leads to one is exciting and deserves further investigation, particularly when observed in the setting of a well-tolerated agent such as IMM-1-104,” Tanios Bekaii-Saab, MD, leader of the Gastrointestinal Cancer Disease Group for the Mayo Clinic Cancer Center and Medical Oncology consultant at Mayo Clinic in Phoenix, Arizona, stated in the news release.¹

In the phase 2a segment of the ongoing phase 1/2a clinical trial, IMM-1-104 is being evaluated both as a monotherapy and in combination with other chemotherapeutic agents. In the phase 2a portion of this study, there are 5 arms: one arm for patients with RAS-mutant melanoma, another for those with RAS-mutant non-small cell lung cancer, and 3 dedicated to patients with pancreatic cancer.

Furthermore, the news release noted that 4 of the 5 treated patients with pancreatic cancer had a known MAPK pathway mutation variants, including KRAS G12V (n = 2), KRAS G12R (n = 1), and GNAS T105Vfs*3 (n = 1).

“These exciting early clinical findings are consistent with the preclinical data we shared at AACR earlier [in 2024], which pointed to synergies between IMM-1-104 and chemotherapeutics, driving deeper more durable responses than either can achieve alone,” Brett Hall, PhD, chief scientific officer of Immuneering, added in the news release. “If the combination data for IMM-1-104 continues to be positive—and taking into account the excellent emerging safety profile for IMM-1-104—one can imagine the drug’s potential inclusion in various vertical drug combinations, immune-modifying combinations, and orthogonal combinations with therapeutics with non-overlapping mechanisms of action, which Immuneering may in the future develop both on its own and in partnership with third parties.”

Treatment with the IMM-1-104 and modified gemcitabine/nab-paclitaxel combination has been well tolerated to date, showcasing a safety profile consistent with established data for chemotherapies. Therefore, based on the safety data reported thus far, the trial’s Data and Safety Monitoring Board has approved the enrollment of additional patients into this arm at a dosage of 320 mg once per day following success with the 240-mg dose.The first patients have already received their doses at 320 mg and are awaiting initial scans.

“Looking at the bigger picture, our phase 2a trial aims to evaluate the efficacy of IMM-1-104 in multiple settings across various tumor types, to identify the highest priority opportunities for future development. If the early trends with IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel continue, we will have an exciting direction for potential future development of IMM-1-104, which could greatly improve the prognosis for a drastically underserved patient population,” Zeskind stated.

Initial data from 1 additional arm of the phase 1/2a investigation on IMM-1-104 is expected by the end of 2024.

References

1. Immuneering announces positive initial phase 2a Data including complete and partial responses with IMM-1-104 in combination with chemotherapy in first-line pancreatic cancer patients. Immuneering Corporation. September 12, 2024. Accessed September 13, 2024. https://ir.immuneering.com/news-releases/news-release-details/immuneering-announces-positive-initial-phase-2a-data-including
2. Immuneering granted FDA fast track designation for IMM-1-104 in first-line pancreatic cancer. News release. Immuneering. July 31, 2024. Accessed September 13, 2024. https://ir.immuneering.com/news-releases/news-release-details/immuneering-granted-fda-fast-track-designation-imm-1-104-first