IMM-1-104 Treatment May Improve Responses in Pancreatic Cancer

Author(s):

Spencer Feldman

Fact checked by:

Ryan Scott

Key Takeaways

IMM-1-104 combined with mGnP shows promising efficacy and tolerability in first-line pancreatic cancer, with a 43% ORR and 86% DCR among seven patients.
IMM-1-104 demonstrated target lesion shrinkage in first-line pancreatic cancer, including a 100% reduction in one patient, supporting further development.
In second-line pancreatic cancer, IMM-1-104 monotherapy achieved disease control in 11 of 21 patients, with rash as the most common side effect.
Immuneering plans to expand phase 2a trials with new combination arms, targeting BRAF-mutant melanoma and non-small cell lung cancer.

A phase 2a trial of IMM-1-104 plus chemotherapy demonstrated efficacy and tolerability in first- and second-line pancreatic cancer.

A phase 2a trial of IMM-1-104 plus chemo demonstrated efficacy and tolerability in pancreatic cancer.

Among patients with first-line pancreatic cancer, treatment of IMM-1-104 in combination with modified Gemzar plus Abraxane (gemcitabine plus nab-paclitaxel, mGnP) demonstrated both efficacious and tolerable outcomes in an ongoing phase 2a trial, according to a press release from Immuneering Corporation.

Following the release, the corporation plans to expand the phase 2a trial to include three additional combination groups.

Glossary:

Overall Response Rate (ORR): percentage of patients with tumor shrinkage (partial or complete response).

Disease Control Rate (DCR): percentage of patients with tumor shrinkage or stable disease.

“Immuneering’s phase 2a data in first-line pancreatic cancer are very promising,” Dr. Tanios Bekaii-Saab said in the release. “If current trends continue, the combination of IMM-1-104 with modified [Gemzar plus Abraxane] may provide improved efficacy and tolerability versus [Gemzar plus Abraxane alone] in the first-line pancreatic cancer setting, where patients continue to urgently need better options. In addition, having a MEK inhibitor that appears to be as well-tolerated as IMM-1-104 may provide new opportunities for patients with different types of cancer.”

Bekaii-Saab is the leader of the Gastrointestinal Cancer Program at Mayo Clinic Comprehensive Cancer Center, in Phoenix, Arizona, as well as the medical director of the Cancer Clinical Research Office and the Vice Chair and Section Chief for Medical Oncology in the Department of Internal Medicine at the Mayo Clinic.

More than 75 patients have been enrolled across all three phase 2a pancreatic cancer trial groups.

Of the seven patients with first-line pancreatic cancer treated with IMM-1-104 combined with mGnP achieved, updated data showed a 43% overall response rate (ORR; 3 patients) and an 86% disease control rate (DCR; 6 patients). Four patients remain on treatment.

Additionally, initial results with IMM-1-104 and modified FOLFIRINOX (mFFX) show target lesion shrinkage in all evaluable patients with first-line pancreatic cancer, including a 100% reduction in one patient.

Among the 21 evaluable patients with second-line pancreatic cancer treated with IMM-1-104 as a monotherapy, 11 achieved disease control, including one instance with a 67% reduction in target lesions, supporting continued development in first-line combination treatments.

In those with second-line pancreatic cancer (21 patients), rash was the most common side effect, occurring in 29% (6 patients) of patients. Other side effects included diarrhea (24%; 5 patients), fatigue (19%; 4 patients), nausea or vomiting (14%; 3 patients) and blurred vision (14%; 3 patients).

“Importantly, we continue to observe a highly differentiated safety profile for IMM-1-104, which we designed to be better tolerated and more active than existing approved MEK inhibitors…,” said Ben Zeskind, CEO of Immuneering. “Accordingly, we plan to add three new phase 2a combination arms: IMM-1-104 with a BRAF inhibitor in BRAF-mutant melanoma, and IMM-1-104 with an immune checkpoint inhibitor in both melanoma and [non-small cell lung cancer].”

The Phase 3 MPACT study established benchmarks for Gemzar plus Abraxane alone in patients with first-line pancreatic cancer. It found one complete response among 431 patients, a 23% ORR and a 48% DCR. Benchmarks for mGnP, a less intensive regimen used in the phase 2 combination group of the IMM-1-104 study, include an 18.6% ORR.

Currently, Immuneering is evaluating the 320 milligram dose, taken every day, of IMM-1-104 in combination with mFFX, according to the release.

“Today we are setting a path to break new ground in indications where no MEK inhibitors have been approved, including pancreatic cancer, and aim to provide a better tolerated and more effective alternative where MEK inhibitors are already helping patients,” concluded Zeskind.

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