IMM-1-104 Earns FDA Fast Track Designation in Pancreatic Cancer

"The FDA’s decision reinforces the importance of developing effective, novel treatments to improve the health outcomes of patients with [PDAC]," according to Vincent Chung, MD, FACP.

The FDA has granted fast track designation to IMM-1-104 as a treatment for patients with pancreatic ductal adenocarcinoma (PDAC) who have progressed following 1 prior line of therapy, according to a press release from Immuneering Corporation.¹

The novel agent is currently under assessment for those with pancreatic cancer and other disease types associated with the RAS pathway as part of a phase 1/2a study (NCT05585320).

By cyclically inhibiting the MAPK pathway via oral dosing once a day, IMM-1-104 is believed to elicit universal RAS activity.

“The FDA’s decision reinforces the importance of developing effective, novel treatments to improve the health outcomes of patients with [PDAC],” principal investigator Vincent Chung, MD, FACP, a professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, said in the press release.¹ “The development of well-tolerated oral medicines would improve the lives of these patients.”

Investigators of the open-label, multicenter, nonrandomized trial will evaluate the anti-tumor activity and safety of IMM-1-104 in patients with previously treated RAS-mutated advanced or metastatic solid tumors across 3 treatment groups. In group A, patients will receive IMM-1-104 orally once a day in 28-day treatment cycles. Patients in group B will receive IMM-1-104 plus gemcitabine at 1000 mg/m² and nab-paclitaxel at 125 mg/m². In group C, patients will receive IMM-1-104 plus folinic acid at 400 mg/m², fluorouracil at 2400 mg/m², irinotecan at 150 mg/m², and oxaliplatin at 85 mg/m² (modified FOLFIRINOX).

The study’s primary end points include adverse effects (AEs), dose-limiting toxicities, and the recommended phase 2 dose (RP2D) in phase 1 as well as the overall response rate per RECIST v1.1 criteria in phase 2a. Secondary end points include disease control rate, progression-free survival, duration of response, and overall survival.

Patients 18 years and older with histologically or cytologically confirmed locally advanced unresectable or metastatic PDAC are eligible for enrollment in the combination therapy cohorts across both phases. Additional eligibility criteria include having evidence of measurable disease per RECIST v1.1 guidelines, an ECOG performance status of 0 or 1, and adequate organ function.

Those with symptomatic, untreated, or actively progressive central nervous system metastases or evidence of retinal vein occlusion are unable to enroll on the study. Patients are also unsuitable for enrollment if they have impaired cardiovascular function or an active skin disorder requiring management within 3 months of study entry.

“We welcome the FDA’s decision to grant fast track designation for IMM-1-104. Our phase 1/2a study is designed to evaluate IMM-1-104 in pancreatic cancer, as well as a number of other tumor types associated with the RAS pathway,” Ben Zeskind, PhD, co-founder, and chief executive officer at Immuneering, said in the press release.¹ “We look forward to a data-rich 2024 as we plan to provide multiple readouts from our study this year.”

Developers previously presented preclinical data on IMM-1-104 administered across 193 tumor models spanning 20 types of tumors in the humanized 3D-tumor growth assay (TGA) at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.² IMM-1-104 monotherapy elicited responses across a variety of MAPK-driven tumor types, which included those harboring RAS or RAF mutations. Additionally, combining the agent with encorafenib (Braftovi) produced tumor growth inhibition rates ranging from 89.8% to 95.2%.

“We believe that IMM-1-104 and IMM-6-415, alone, and in combination with other agents, have the potential to bring significant benefit to broad populations of patients with RAS or RAF mutant cancers,” Zeskind said in a press release on these data.²

References

1. Immuneering receives FDA fast track designation for IMM-1-104 in pancreatic cancer. News release. Immuneering Corporation. February 20, 2024. Accessed February 22, 2024. https://bit.ly/3wrgkCW
2. Immuneering presents preclinical data demonstrating encouraging anti-tumor activity for IMM-1-104 and IMM-6-415 at AACR-NCI-EORTC Conference. Immuneering Corporation. October 12, 2023. Accessed February 22, 2024. https://bit.ly/3wuG6X2