Advanced Solid TumorPhase 1/2NCT05585320
A Phase 1/2a Study of IMM-1-104 in Participants With Advanced or Metastatic Solid Tumors
A Phase 1/2 study testing IMM-1-104 Monotherapy (Treatment Group A), IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B) and IMM-1-104 + modified FOLFIRINOX (Treatment Group C) in people with Advanced Solid Tumor and Pancreatic Adenocarcinoma, run by Immuneering Corporation at 20 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Pancreatic Adenocarcinoma, Malignant Melanoma (Cutaneous)
- What is being tested?
- IMM-1-104 Monotherapy (Treatment Group A), IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B) and IMM-1-104 + modified FOLFIRINOX (Treatment Group C)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 209 participants
- Where
- 20 sitesUnited States
- Study dates
- 31 Oct 2022to Jun 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ function
Who cannot join
- 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
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- 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.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Levine Cancer Center
Charlotte, North Carolina, 28204
Northwestern University
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
Sarah Cannon Research Institute
Denver, Colorado, 80218
City of Hope
Duarte, California, 91010
Duke University Cancer Institute
Durham, North Carolina, 27710
Hematology Oncology Associates of Central New York
East Syracuse, New York, 13057
NEXT Oncology
Fairfax, Virginia, 22031
MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic
Jacksonville, Florida, 32224
Florida Cancer Specialists and Research Institute
Lake Mary, Florida, 32746
University of Wisconsin Clinical Science Center
Madison, Wisconsin, 53792
SCRI Oncology Partners
Nashville, Tennessee, 27203
Weill Cornell Medicine
New York, New York, 10021
Mayo Clinic
Rochester, Minnesota, 55905
NEXT Oncology
San Antonio, Texas, 78229
University of California San Diego
San Diego, California, 92037
Sarcoma Oncology Center
Santa Monica, California, 90403
Mayo Clinic
Scottsdale, Arizona, 85259
About this study
Official title: 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
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.
- Conditions
- Advanced Solid Tumor, Pancreatic Adenocarcinoma, Malignant Melanoma (Cutaneous), Non-small Cell Lung Cancer (NSCLC)
- Being tested
- IMM-1-104 Monotherapy (Treatment Group A), IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B), IMM-1-104 + modified FOLFIRINOX (Treatment Group C), IMM-1-104 + dabrafenib (Treatment Group D), IMM-1-104 + pembrolizumab (Treatment Group E)
- Keywords
- pan-RAS, KRAS, NRAS, HRAS, Targeted therapy, Metastatic cancer, Advanced cancer, RAS, Adenocarcinoma, MEK, Dual MEK, MEK 1/2, Mitogen-Activated Protein Kinase (MAPK), G12A, G12C, G12D, G12F, G12R, G12S, G12V
- Medical subject headings
- Melanoma, Cutaneous Malignant, Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMM-1-104 Monotherapy (Treatment Group A)Drug
Also called IMM-1-104
Once-daily, oral IMM-1-104 dose administered in 28-day cycles until treatment discontinuation criteria are met
IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B)Drug
Also called IMM-1-104 + mGnP
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
IMM-1-104 + modified FOLFIRINOX (Treatment Group C)Drug
Also called IMM-1-104 + mFFX
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
IMM-1-104 + dabrafenib (Treatment Group D)Drug
Also called IMM-1-104 + dabrafenib
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).
IMM-1-104 + pembrolizumab (Treatment Group E)Drug
Also called IMM-1-104 + pembro
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.
| Study group | Role | What they receive |
|---|---|---|
| IMM-1-104 monotherapy (Treatment Group A) | Experimental | IMM-1-104 monotherapy for first/second line pancreatic adenocarcinoma; first/second/third line melanoma; or second/third line non small cell lung cancer Receives: Drug: IMM-1-104 Monotherapy (Treatment Group A) |
| IMM-1-104 in combination with mGnP (Treatment Group B) | Experimental | IMM-1-104 in combination with modified gemcitabine and nab-paclitaxel (mGnP) for first line pancreatic adenocarcinoma Receives: Drug: IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B) |
| IMM-1-104 in combination with mFFX (Treatment Group C) | Experimental | IMM-1-104 in combination with modified FOLFIRINOX (mFFX) for first line pancreatic adenocarcinoma Receives: Drug: IMM-1-104 + modified FOLFIRINOX (Treatment Group C) |
| IMM-1-104 in combination with dabrafenib (Treatment Group D) | Experimental | IMM-1-104 in combination with dabrafenib for second/third line post-IO melanoma with BRAF mutation Receives: Drug: IMM-1-104 + dabrafenib (Treatment Group D) |
| IMM-1-104 in combination with pembrolizumab (Treatment Group E) | Experimental | IMM-1-104 in combination with pembrolizumab for second/third line post-IO melanoma Receives: Drug: IMM-1-104 + pembrolizumab (Treatment Group E) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Adverse Events
Number of participants with adverse events
Measured: 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
Measured: 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
Measured: 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
Measured: After up to 48 weeks (12 cycles) of study treatment
Secondary outcomes (9)
Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104
Cmax
Measured: After 12 weeks (3 Cycles) of study treatment
Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104
Tmax
Measured: After 12 weeks (3 Cycles) of study treatment
Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104
AUC0-t
Measured: After 12 weeks (3 Cycles) of study treatment
Phase 2a: Disease Control Rate (DCR)
The proportion of participants who have a best overall response (BOR) of stable disease (SD) or better
Measured: After 16 weeks (4 Cycles) of study treatment
Phase 2a: Progression Free Survival (PFS)
The time interval between study treatment start and disease progression or death due to any cause.
Measured: Up to approximately 2 years
Phase 2a: Duration of Response (DOR)
The time interval between an assessment of partial response (PR) or better and disease progression or death due to any cause.
Measured: Up to approximately 2 years.
Phase 2a: Landmark 3-Month Survival
The proportion of participants who are still alive after three months on study.
Measured: After 3 months of study participation.
Phase 2a: Landmark 6-Month Survival
The proportion of participants who are still alive after six months on study.
Measured: After 6 months of study participation.
Phase 2a: Overall Survival (OS)
The time interval between study treatment start and death due to any cause.
Measured: Up to approximately 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2022
- Study start31 Oct 2022
- Primary completionJun 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 209 participants (actual)
Sponsor and investigators
- Lead sponsor
- Immuneering Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vinny Hayreh, MD, Study director, Immuneering Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05585320
- Sponsor's protocol ID
- IMM1104-101
- Status last verified
- Oct 2026
- First submitted
- 14 Oct 2022
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No