Sponsor: Immuneering Corporation (industry)
Phase: 3
Start date: May 1, 2026
Planned enrollment: 510
Show Summary from Sponsor
Show for: Atebimetinib (IMM-1-104, TEL9243A3N, 2669009-92-9)
IMM-1-104 (also called atebimetinib) is an oral, small-molecule dual-MEK inhibitor being developed by Immuneering for cancers driven by RAS/MAPK pathway activation. A first-in-human, open-label phase 1/2a study (NCT05585320) started in October 2022 and is ongoing across multiple solid tumors, including dedicated pancreatic ductal adenocarcinoma (PDAC) cohorts. (clinicaltrials.ucsd.edu)
IMM-1-104 is a selective, allosteric “dual‑MEK” inhibitor engineered to suppress phosphorylation of MEK and its downstream target ERK, aiming to blunt MAPK signaling and resist CRAF-mediated pathway reactivation. It is designed with a short plasma half‑life to produce once‑daily “deep cyclic inhibition” (DCI): high-level, time‑limited target suppression followed by recovery, with the goal of improving tolerability while limiting adaptive resistance. Preclinical and translational data demonstrate reduced pMEK and pERK across RAS- and RAF‑mutant models and support the DCI pharmacology. (aacrjournals.org)
Phase 1 (dose escalation; advanced RAS‑mutant solid tumors): As of February 20, 2024, initial activity signals included target lesion regression in 53% of patients treated at 240 or 320 mg QD; best individual lesion regression was −35.7% and best RECIST SLD change was −18.9%. Immune monitoring via ctDNA showed no new acquired RAS alterations among evaluable patients (n=22). The 320 mg QD dose was selected as the candidate RP2D. (ir.immuneering.com)
Phase 2a (PDAC cohorts):
Peer‑reviewed clinical efficacy publications are not yet available; early data have been shared via company releases and media summaries. (immuneering.gcs-web.com)
Phase 1: IMM-1-104 was generally well tolerated. Among treatment‑related adverse events (TRAEs) ≥10%, most were grade 1–2; no grade 4 TRAEs, one non‑serious grade 3 rash, no serious TRAEs, and no dose‑limiting toxicities were reported at the time of the topline analysis (n=41 as of Feb 20, 2024). Pharmacodynamic data showed ≥90% transient pERK inhibition at 320 mg (≈2.7 hours) and 240 mg (≈1.9 hours), consistent with DCI. (ir.immuneering.com)
Early phase 2a (PDAC combinations): Company updates describe a “markedly favorable tolerability profile” for atebimetinib + mGnP; detailed AE tables are pending peer‑reviewed presentation. (immuneering.gcs-web.com)
Notes: Data above reflect interim, nonrandomized early‑phase results reported between March 2024 and September 2025; confirm at future peer‑reviewed meetings/publications as they become available. (globenewswire.com)
Last updated: Oct 2025
Goal: Evaluate whether adding atebimetinib to a modified gemcitabine plus nab-paclitaxel regimen improves outcomes compared with standard gemcitabine plus nab-paclitaxel as first-line therapy for metastatic pancreatic ductal adenocarcinoma, with overall survival as the primary efficacy endpoint and safety also assessed.
Patients: Adults at least 18 years old with metastatic pancreatic adenocarcinoma, ECOG performance status 0 or 1, measurable disease by RECIST v1.1, adequate organ and coagulation function, and no prior systemic anticancer therapy for metastatic disease. Key exclusions include non-adenocarcinoma pancreatic histologies such as squamous, adenosquamous, neuroendocrine, or acinar carcinoma; locally advanced disease without metastases; inability to swallow oral medication; and symptomatic, untreated, or actively progressing CNS metastases.
Design: Global, randomized, open-label phase 3 trial enrolling treatment-naive patients with metastatic pancreatic adenocarcinoma. Participants are assigned to either experimental atebimetinib plus modified gemcitabine/nab-paclitaxel or active comparator standard gemcitabine/nab-paclitaxel, with follow-up for efficacy, safety, and quality of life for up to approximately 2 years.
Treatments: The experimental arm receives atebimetinib in combination with a modified schedule of gemcitabine and nab-paclitaxel. Atebimetinib, also known as IMM-1-104, is an investigational oral dual MEK1/2 inhibitor targeting the MAPK pathway, a key downstream pathway in RAS-mutant tumors including most pancreatic ductal adenocarcinomas. It is designed for deep cyclic MAPK pathway inhibition with a short half-life, aiming to inhibit tumor signaling while allowing pathway recovery in normal tissues. Early phase data in advanced solid tumors showed mostly grade 1–2 treatment-related adverse events, with initial evidence of target-lesion regression at active doses; preliminary first-line pancreatic cancer combination data reported responses in a small cohort, including an overall response rate of 40% among the first 5 patients treated. The control arm receives standard gemcitabine plus nab-paclitaxel, an established first-line chemotherapy regimen for metastatic pancreatic adenocarcinoma.
Outcomes: The primary endpoint is overall survival comparing atebimetinib plus modified gemcitabine/nab-paclitaxel versus standard gemcitabine/nab-paclitaxel. Secondary endpoints include progression-free survival, overall response rate, disease control rate, incidence of adverse events graded by CTCAE v6, and quality of life using the EORTC QLQ-C30 global health status and functional/symptom scales.
Burden on patient: The expected patient burden is moderate. Treatment requires standard intravenous chemotherapy visits for gemcitabine and nab-paclitaxel, with the experimental arm also adding daily oral atebimetinib and potential additional monitoring for MEK inhibitor–associated toxicities such as rash, diarrhea, edema, ocular effects, and laboratory abnormalities. As a phase 3 study, the assessment schedule is likely similar to standard oncology practice, including periodic imaging, laboratory testing, adverse-event assessments, and quality-of-life questionnaires, without the intensive pharmacokinetic sampling or mandatory serial biopsies typical of early-phase trials. The main incremental burden is the oral investigational agent, additional safety monitoring, and trial-related documentation rather than substantially more invasive procedures.
Last updated: May 2026
Show Criteria
Inclusion Criteria:
* Must be ≥18 years of age
* Must have confirmed diagnosis according to AJCC staging as follows:
* Metastatic pancreatic adenocarcinoma at least 12 weeks prior to screening
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Participants must be treatment naive as follows:
* First-line PDAC participants will have received no previous systemic anti-cancer therapy
* Must have evidence of measurable disease (at least one target lesion) per RECIST v1.1 criteria
* Adequate organ function, hepatic function, coagulation studies and protocol determined clinical laboratory values
Exclusion Criteria:
* Inability to swallow oral medications
* Participant has squamous, adenosquamous, neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma
* Participants with only locally advanced disease
* Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases
Phoenix, Arizona, 85338, United States
[email protected] / No phone
Status: Recruiting
Duarte, California, 91010, United States
No email / No phone
Status: Recruiting
Chicago, Illinois, 60099, United States
No email / No phone
Status: Recruiting
New York, New York, 10016, United States
[email protected] / No phone
Status: Recruiting
Maumee, Ohio, 43537, United States
[email protected] / No phone
Status: Recruiting
Nashville, Tennessee, 37203, United States
[email protected] / No phone
Status: Recruiting
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