A Phase 1/2a Study of IMM-1-104 in Participants With Previously Treated, RAS-Mutant, Advanced or Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT05585320
• Recruitment Status: Recruiting
• First Posted: October 18, 2022
• Last Update Posted: April 30, 2024
• Sponsor: Immuneering Corporation
• Information provided by (Responsible Party): Immuneering Corporation

Study Description

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 dose (RP2D) 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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor; Pancreatic Adenocarcinoma; Malignant Melanoma (Cutaneous); Non-small Cell Lung Cancer (NSCLC)	Drug: IMM-1-104 Monotherapy (Treatment Group A); Drug: IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B); Drug: IMM-1-104 + modified FOLFIRINOX (Treatment Group C)	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 210 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Previously Treated RAS-Mutated Advanced or Metastatic Solid Tumors
• Actual Study Start Date: October 31, 2022
• Estimated Primary Completion Date: June 2026
• Estimated Study Completion Date: June 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: 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; Other Name: IMM-1-104
Experimental: 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	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; Other Name: IMM-1-104 + mGnP
Experimental: IMM-1-104 in combination with mFFX (Treatment Group C); IMM-1-104 in combination with modified FOLFIRINOX (mFFX) for first line pancreatic adenocarcinoma	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; Other Name: IMM-1-104 + mFFX

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Adverse Events [ Time Frame: From treatment initiation through 30 days following the last IMM-1-104 dose ]
   Number of participants with adverse events
2. Phase 1: Dose-Limiting Toxicities [ Time Frame: The first 21 days of study treatment ]
   Number of participants with dose-limiting toxicities
3. Phase 1: Recommended Phase 2 Dose (RP2D) candidate [ Time Frame: Initiation of study treatment through 21 days (up to approximately 18 months) ]
   Selection of candidate RP2D to take forward into Ph2a
4. Phase 2a: Overall Response Rate [ Time Frame: After up to 48 weeks (12 cycles) of study treatment ]
   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

Secondary Outcome Measures :

1. Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104 [ Time Frame: After 12 weeks (3 Cycles) of study treatment ]
   Cmax
2. Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104 [ Time Frame: After 12 weeks (3 Cycles) of study treatment ]
   Tmax
3. Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104 [ Time Frame: After 12 weeks (3 Cycles) of study treatment ]
   AUC0-t
4. Phase 2a: Disease Control Rate (DCR) [ Time Frame: After 16 weeks (4 Cycles) of study treatment ]
   The proportion of participants who have a best overall response (BOR) of stable disease (SD) or better
5. Phase 2a: Progression Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
   The time interval between study treatment start and disease progression or death due to any cause.
6. Phase 2a: Duration of Response (DOR) [ Time Frame: Up to approximately 2 years. ]
   The time interval between an assessment of partial response (PR) or better and disease progression or death due to any cause.
7. Phase 2a: Landmark 3-Month Survival [ Time Frame: After 3 months of study participation. ]
   The proportion of participants who are still alive after three months on study.
8. Phase 2a: Landmark 6-Month Survival [ Time Frame: After 6 months of study participation. ]
   The proportion of participants who are still alive after six months on study.
9. Phase 2a: Overall Survival (OS) [ Time Frame: Up to approximately 2 Years ]
   The time interval between study treatment start and death due to any cause.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• 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
• Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.

Contacts and Locations

Contacts

Contact: IMM1104-101 Study Team; (860) 321-1302; clinicaltrials@immuneering.com

Locations

United States, California

City of Hope; Recruiting

Duarte, California, United States, 91010

Principal Investigator: Vincent Chung, MD

University of California San Diego; Not yet recruiting

San Diego, California, United States, 92037

Principal Investigator: Peter Vu, MD

Sarcoma Oncology Center; Recruiting

Santa Monica, California, United States, 90403

Principal Investigator: Sant Chawla, MD

United States, Florida

Florida Cancer Specialists and Research Institute; Recruiting

Lake Mary, Florida, United States, 32746

Principal Investigator: Alexander Philipovskiy, MD

United States, Illinois

Northwestern University; Recruiting

Chicago, Illinois, United States, 60611

Principal Investigator: Sunandana Chandra, MD

United States, Massachusetts

Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator: Elizabeth Buchbinder, MD

United States, New York

Hematology Oncology Associates of Central New York; Recruiting

East Syracuse, New York, United States, 13057

Principal Investigator: Steven Duffy, MD

Weill Cornell Medicine; Recruiting

New York, New York, United States, 10021

Principal Investigator: Anna Pavlick, DO

United States, North Carolina

Duke University Cancer Institute; Not yet recruiting

Durham, North Carolina, United States, 27710

Principal Investigator: Jeffrey Clarke, MD

United States, Tennessee

SCRI Oncology Partners; Recruiting

Nashville, Tennessee, United States, 27203

Principal Investigator: Melissa Johnson, MD

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Principal Investigator: Shubham Pant, MD

NEXT Oncology; Recruiting

San Antonio, Texas, United States, 78229

Principal Investigator: David Sommerhalder, MD

United States, Virginia

NEXT Oncology; Recruiting

Fairfax, Virginia, United States, 22031

Principal Investigator: Alex Spira, MD, PhD

Sponsors and Collaborators

Immuneering Corporation

Investigators

• Study Director: Vinny Hayreh, MD; Immuneering Corporation

More Information

• Responsible Party: Immuneering Corporation
• ClinicalTrials.gov Identifier: NCT05585320
• Other Study ID Numbers: IMM1104-101
• First Posted: October 18, 2022
• Last Update Posted: April 30, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Immuneering Corporation:

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; G13C; G13D; G13R; Q61H; Q61K; Q61L; Q61R; A146T; A146V; K117N

Additional relevant MeSH terms:

Melanoma; Adenocarcinoma; Neoplasms; Neoplasms by Site; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Paclitaxel; Gemcitabine; Folfirinox; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites