A Phase 1/2a Study of IMM-1-104 in Participants With Advanced or Metastatic Solid Tumors
A Phase 1/2a, Open-Label, Multicenter, Nonrandomized, Safety and Anti-tumor Activity Study of IMM-1-104, a Novel Oral Dual MEK1/2 Inhibitor in Participants With Advanced or Metastatic Solid Tumors
1 other identifier
interventional
209
1 country
20
Brief Summary
This is an open-label, dose-exploration and expansion study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of IMM-1-104 when administered as monotherapy or in combination with approved agents in participants with RAS-mutated or RAS/MAPK activated advanced or metastatic solid tumors. The dose exploration will identify the candidate recommended Phase 2 candidate optimal dose of IMM-1-104 to further explore the anti-tumor activity of IMM-1-104 as monotherapy and in combination with approved agents in multiple Phase 2a proof-of-concept cohorts in malignancies of interest.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2022
Longer than P75 for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 14, 2022
CompletedFirst Posted
Study publicly available on registry
October 18, 2022
CompletedStudy Start
First participant enrolled
October 31, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
September 2, 2025
August 1, 2025
3.6 years
October 14, 2022
August 29, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Phase 1: Adverse Events
Number of participants with adverse events
From treatment initiation through 30 days following the last IMM-1-104 dose
Phase 1: Dose-Limiting Toxicities
Number of participants with dose-limiting toxicities
The first 21 days of study treatment
Phase 1: Recommended Phase 2 Candidate Optimal Dose
Selection of candidate optimal dose to take forward into Ph2a
Initiation of study treatment through 21 days (up to approximately 18 months)
Phase 2a: Overall Response Rate
The proportion of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR), based on RECIST 1.1 criteria
After up to 48 weeks (12 cycles) of study treatment
Secondary Outcomes (9)
Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104
After 12 weeks (3 Cycles) of study treatment
Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104
After 12 weeks (3 Cycles) of study treatment
Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104
After 12 weeks (3 Cycles) of study treatment
Phase 2a: Disease Control Rate (DCR)
After 16 weeks (4 Cycles) of study treatment
Phase 2a: Progression Free Survival (PFS)
Up to approximately 2 years
- +4 more secondary outcomes
Study Arms (5)
IMM-1-104 monotherapy (Treatment Group A)
EXPERIMENTALIMM-1-104 monotherapy for first/second line pancreatic adenocarcinoma; first/second/third line melanoma; or second/third line non small cell lung cancer
IMM-1-104 in combination with mGnP (Treatment Group B)
EXPERIMENTALIMM-1-104 in combination with modified gemcitabine and nab-paclitaxel (mGnP) for first line pancreatic adenocarcinoma
IMM-1-104 in combination with mFFX (Treatment Group C)
EXPERIMENTALIMM-1-104 in combination with modified FOLFIRINOX (mFFX) for first line pancreatic adenocarcinoma
IMM-1-104 in combination with dabrafenib (Treatment Group D)
EXPERIMENTALIMM-1-104 in combination with dabrafenib for second/third line post-IO melanoma with BRAF mutation
IMM-1-104 in combination with pembrolizumab (Treatment Group E)
EXPERIMENTALIMM-1-104 in combination with pembrolizumab for second/third line post-IO melanoma
Interventions
Once-daily, oral IMM-1-104 dose administered in 28-day cycles until treatment discontinuation criteria are met
Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of gemcitabine and nab-paclitaxel until treatment discontinuation criteria are met. Gemcitabine will be administered at a dose of 1000 mg/m\^2 nab-Paclitaxel will be administered at a dose of 125 mg/m\^2
Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of modified FOLFIRNOX until treatment discontinuation criteria are met. FOLFIRINOX will be administered as follows: Folinic Acid will be administered at 400 mg/m\^2 Fluorouracil will be administered at 2400 mg/m\^2 Irinotecan will be administered at 150 mg/m\^2 Oxaliplatin will be administered at 85 mg/m\^2
Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with twice daily oral dose of dabrafenib until treatment discontinuation criteria are met. Dabrafenib will be administered at a dose of 150mg daily (75mg twice daily).
Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of pembrolizumab in sequence or concurrently depending on the enrolled cohort (two sub cohorts) until treatment discontinuation criteria are met. Pembrolizumab will be administered at a dose of 400mg.
Eligibility Criteria
You may qualify if:
- Must be ≥18 years of age
- Must have histologically or cytologically confirmed diagnosis as follows:
- Monotherapy Phase 1: A locally advanced unresectable or metastatic solid tumor malignancy that harbors a RAS (KRAS, NRAS, or HRAS) activating mutation.
- Monotherapy Phase 2a: A locally advanced unresectable or metastatic solid tumor malignancies: pancreatic ductal adenocarcinoma (PDAC), RAS-mutant melanoma, or RAS-mutant non-small cell lung cancer (NSCLC)
- Combination therapy (both phases): A locally advanced unresectable or metastatic PDAC
- Combination therapy Phase 2a, Treatment D: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma with BRAF mutation. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb.
- Combination therapy Phase 2a, Treatment E: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb.
- Participants must be treatment naive or received prior systemic standard-of-care treatment as follows:
- Monotherapy Phase 1: received at least 1 line of systemic standard-of-care treatment for their advanced or metastatic disease
- Monotherapy Phase 2a:
- First-line PDAC participants will have received no previous systemic anti-cancer therapy. Second-line PDAC participants will have received no more than one prior systemic anti-cancer therapy.
- First-line melanoma participants will have received no previous systemic anti-cancer therapy. Second- and third-line participants will have received and failed one or two prior systemic anti-cancer therapies, respectively.
- NSCLC participants will have received at least one and no more than two previous lines of systemic therapy.
- Combination therapy (both phases): PDAC participants will have received no previous systemic anti-cancer therapy for their advanced or metastatic disease.
- Must have evidence of measurable disease (at least one target lesion) per RECIST v1.1 criteria
- +2 more criteria
You may not qualify if:
- Inability to swallow oral medications
- Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases
- History or concurrent evidence of retinal vein occlusion (RVO) or current risk factors for RVO. History of serous retinopathy, retinal edema, or retinal pigment epithelial detachment (RPED)
- Impaired cardiovascular function or clinically significant cardiac disease
- History of rhabdomyolysis within 3 months prior to start of study treatment
- Active skin disorder requiring systemic treatment within 3 months prior to the start of study treatment
- Participants with active, uncontrolled autoimmune disease or participants actively being treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors for management of their autoimmune disease are excluded
- Receipt of an allogeneic tissue/solid organ transplant
- Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
Mayo Clinic
Scottsdale, Arizona, 85259, United States
City of Hope
Duarte, California, 91010, United States
University of California San Diego
San Diego, California, 92037, United States
Sarcoma Oncology Center
Santa Monica, California, 90403, United States
Sarah Cannon Research Institute
Denver, Colorado, 80218, United States
Mayo Clinic
Jacksonville, Florida, 32224, United States
Florida Cancer Specialists and Research Institute
Lake Mary, Florida, 32746, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago
Chicago, Illinois, 60637, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Hematology Oncology Associates of Central New York
East Syracuse, New York, 13057, United States
Weill Cornell Medicine
New York, New York, 10021, United States
Levine Cancer Center
Charlotte, North Carolina, 28204, United States
Duke University Cancer Institute
Durham, North Carolina, 27710, United States
SCRI Oncology Partners
Nashville, Tennessee, 27203, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
NEXT Oncology
San Antonio, Texas, 78229, United States
NEXT Oncology
Fairfax, Virginia, 22031, United States
University of Wisconsin Clinical Science Center
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Vinny Hayreh, MD
Immuneering Corporation
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 14, 2022
First Posted
October 18, 2022
Study Start
October 31, 2022
Primary Completion (Estimated)
June 1, 2026
Study Completion (Estimated)
June 1, 2027
Last Updated
September 2, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will not share