A Phase 1/2a Study of IMM-1-104 in Participants With Advanced or Metastatic Solid Tumors

NCT ID: NCT05585320

Last Updated: 2025-09-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 209 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-31
• Study Completion Date: 2027-06-30

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.

Conditions

Advanced Solid Tumor; Pancreatic Adenocarcinoma; Malignant Melanoma (Cutaneous); Non-small Cell Lung Cancer (NSCLC)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMM-1-104 monotherapy (Treatment Group A)

IMM-1-104 monotherapy for first/second line pancreatic adenocarcinoma; first/second/third line melanoma; or second/third line non small cell lung cancer

Group Type: EXPERIMENTAL

IMM-1-104 Monotherapy (Treatment Group A)

Intervention Type: DRUG

Once-daily, oral IMM-1-104 dose administered in 28-day cycles until treatment discontinuation criteria are met

IMM-1-104 in combination with mGnP (Treatment Group B)

IMM-1-104 in combination with modified gemcitabine and nab-paclitaxel (mGnP) for first line pancreatic adenocarcinoma

Group Type: EXPERIMENTAL

IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B)

Intervention Type: DRUG

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 in combination with mFFX (Treatment Group C)

IMM-1-104 in combination with modified FOLFIRINOX (mFFX) for first line pancreatic adenocarcinoma

Group Type: EXPERIMENTAL

IMM-1-104 + modified FOLFIRINOX (Treatment Group C)

Intervention Type: DRUG

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 in combination with dabrafenib (Treatment Group D)

IMM-1-104 in combination with dabrafenib for second/third line post-IO melanoma with BRAF mutation

Group Type: EXPERIMENTAL

IMM-1-104 + dabrafenib (Treatment Group D)

Intervention Type: DRUG

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 in combination with pembrolizumab (Treatment Group E)

IMM-1-104 in combination with pembrolizumab for second/third line post-IO melanoma

Group Type: EXPERIMENTAL

IMM-1-104 + pembrolizumab (Treatment Group E)

Intervention Type: DRUG

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.

Interventions

IMM-1-104 Monotherapy (Treatment Group A)

Once-daily, oral IMM-1-104 dose administered in 28-day cycles until treatment discontinuation criteria are met

Intervention Type: DRUG

IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B)

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

Intervention Type: DRUG

IMM-1-104 + modified FOLFIRINOX (Treatment Group C)

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

Intervention Type: DRUG

IMM-1-104 + dabrafenib (Treatment Group D)

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).

Intervention Type: DRUG

IMM-1-104 + pembrolizumab (Treatment Group E)

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.

Intervention Type: DRUG

Other Intervention Names

IMM-1-104; IMM-1-104 + mGnP; IMM-1-104 + mFFX; IMM-1-104 + dabrafenib; IMM-1-104 + pembro

Eligibility Criteria

Inclusion Criteria

• Must be ≥18 years of age
• Must have histologically or cytologically confirmed diagnosis as follows:

1. Monotherapy Phase 1: A locally advanced unresectable or metastatic solid tumor malignancy that harbors a RAS (KRAS, NRAS, or HRAS) activating mutation.

2. 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)

3. Combination therapy (both phases): A locally advanced unresectable or metastatic PDAC

4. 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.

5. 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:

1. Monotherapy Phase 1: received at least 1 line of systemic standard-of-care treatment for their advanced or metastatic disease

2. Monotherapy Phase 2a:

1. 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.

2. 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.

3. NSCLC participants will have received at least one and no more than two previous lines of systemic therapy.

3. 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immuneering Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vinny Hayreh, MD

Role: STUDY_DIRECTOR

Immuneering Corporation

Locations

Mayo Clinic

Scottsdale, Arizona, United States

City of Hope

Duarte, California, United States

University of California San Diego

San Diego, California, United States

Sarcoma Oncology Center

Santa Monica, California, United States

Sarah Cannon Research Institute

Denver, Colorado, United States

Mayo Clinic

Jacksonville, Florida, United States

Florida Cancer Specialists and Research Institute

Lake Mary, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Hematology Oncology Associates of Central New York

East Syracuse, New York, United States

Weill Cornell Medicine

New York, New York, United States

Levine Cancer Center

Charlotte, North Carolina, United States

Duke University Cancer Institute

Durham, North Carolina, United States

SCRI Oncology Partners

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

NEXT Oncology

San Antonio, Texas, United States

NEXT Oncology

Fairfax, Virginia, United States

University of Wisconsin Clinical Science Center

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

IMM1104-101

Identifier Type: -

Identifier Source: org_study_id