On September 12, 2024 Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients, reported positive initial response data from the first five patients treated with IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel in first line pancreatic cancer as part of its ongoing Phase 2a clinical trial (Press release, Immuneering, SEP 12, 2024, View Source [SID1234647154]).

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"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 Disease Control Rate 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 five of these initial patients and for additional patients planned to come. Nevertheless, it was encouraging to see a complete response in the very first pancreatic cancer patient treated with IMM-1-104 in this combination, with the patient now on treatment for over six months," said Ben Zeskind, Ph.D., Co-Founder and CEO of Immuneering. "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."

Initial Results from Phase 2a Arm Evaluating IMM-1-104 with Modified Gemcitabine/nab-Paclitaxel in First Line Pancreatic Cancer as of September 12, 2024

Patient MAPK
Mutation
Variant Dose (p.o.)
Level for
IMM-1-104 %
Change
in SLD
1st Scan %
Change
in SLD
2nd Scan %
Change
in SLD
3rd Scan %
Change
in SLD
4th Scan %
Change
in SLD
5th Scan ORR/
RECIST
1 GNAS-T105Vfs*3 (*) 240mg QD -100% -100% -100% -100% next
scan CR
2 KRAS-G12V* 240mg QD -8% -10% -40% next
scan uPR°
3 KRAS-G12V* 240mg QD -4% next
scan SD
4 Unk.# 240mg QD +6% next
scan SD
5 KRAS-G12R* 240mg QD -9% next
scan eqPD**
Initial Overall Response Rate
(ORR): 40%
Initial Disease Control Rate (DCR): 80%

* Detected in plasma cfDNA or prior genomic test.
# Unknown (Unk.); MAPK pathway variant not detected in plasma cfDNA or prior genomic test.
° Partial response result classified as "unconfirmed" pending subsequent scan.
**Equivocal (eq); Patient not dosed for over two weeks during hospitalization for a preexisting condition. Scans showed ascites and a pleural effusion categorized by radiology as equivocal new lesions per RECIST 1.1. The investigator determined these to be related to the recent placement of a hepatic stent, not disease progression, and stated that the patient is improving and remains on therapy.

Source: Immuneering Corporation

To date, the first two patients in the Phase 2a arm evaluating IMM-1-104 with modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer have recorded complete or partial responses for an initial response rate of 40% (2/5) and disease control rate of 80% (4/5), with the other three patients earlier in the course of treatment and all five continuing on treatment.
Benchmarks for gemcitabine/nab-paclitaxel alone in first-line pancreatic cancer patients were established by the Phase 3 MPACT study, which included 1 Complete Response (CR) out of 431 patients, a 23% Overall Response Rate, and a 48% Disease Control Rate1. Benchmarks for modified (m) Gemcitabine/nab-Paclitaxel include an 18.6% ORR2.
To date, the combination of IMM-1-104 plus modified gemcitabine/nab-paclitaxel was observed to be well tolerated, with an emerging safety profile in line with known data for both therapeutics respectively.
Based on safety data to date, the trial’s Data and Safety Monitoring Board (DSMB) has approved enrolling additional patients into this arm at 320mg QD p.o., the first of which have already been dosed and are awaiting first scans.
[1] Von Hoff, et al. N Engl J Med. 2013;369:1691-1703, [2] Ahn DH, et al. Therapeutic Advances in Medical Oncology. 2017;9(2):75-82

"These exciting early clinical findings are consistent with the preclinical data we shared at AACR (Free AACR Whitepaper) earlier this year, which pointed to synergies between IMM-1-104 and chemotherapeutics – driving deeper more durable responses than either can achieve alone," said Brett Hall, Ph.D., Chief Scientific Officer, Immuneering Corporation. "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."

"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 complete responses, 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," said Tanios Bekaii-Saab, M.D., Leader of the Gastrointestinal Cancer Disease Group for the Mayo Clinic Cancer Center enterprise wide and Medical Oncology consultant in Mayo Clinic in Phoenix, Arizona.

In the Phase 2a portion of Immuneering’s ongoing IMM-1-104 Phase 1/2a clinical trial, IMM-1-104 is being evaluated as both monotherapy and in combination with approved chemotherapeutic agents. The Phase 2a portion includes five arms, one of which focuses on patients with RAS mutant melanoma, another on patients with RAS mutant non-small cell lung cancer (NSCLC), and three arms focused on patients with pancreatic cancer. Immuneering previously announced that IMM-1-104 received fast track designation for the treatment of first- and second-line pancreatic cancer.

Near-Term Milestone Expectations

IMM-1-104

Initial data from at least one additional arm of the Phase 2a portion of the Company’s Phase 1/2a trial is expected by year end.

IMM-6-415

Initial pharmacokinetic (PK), pharmacodynamic (PD) and safety data from the Phase 1 portion of the Company’s Phase 1/2a trial is expected by year end.

Conference Call

Immuneering will host a conference call and live webcast at 4:30 p.m. ET / 1:30 p.m. PT on September 12, 2024, to discuss the results and provide a business update. Individuals interested in listening to the live conference call may do so by dialing (800) 715-9871 for U.S callers and (646) 307-1963 for other locations and reference conference ID 8890310, or from the webcast link in the "investors" section of the company’s website at www.immuneering.com A webcast replay will be available in the investor relations section on the company’s website for 90 days following the completion of the call.

About IMM-1-104

IMM-1-104 aims to achieve universal-RAS activity that selectively impacts cancer cells to a greater extent than healthy cells, through Deep Cyclic Inhibition of the MAPK pathway with once-daily dosing. IMM-1-104 is currently being evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations (NCT05585320).