A Phase 1/2a Study of IMM-1-104 in Participants With Previously Treated, RAS-Mutant, 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 Previously Treated RAS-Mutated 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 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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Adenocarcinoma; Advanced Solid Tumor; Non-small Cell Lung Cancer (NSCLC); Malignant Melanoma (Cutaneous)
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: IMM1104-101 Study Team; Phone Number: (860) 321-1302; Email: clinicaltrials@immuneering.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Principal Investigator: Vincent Chung, MD
    • San Diego, California, United States, 92037
      • Not yet recruiting
      • University of California San Diego
      • Principal Investigator: Peter Vu, MD
    • Santa Monica, California, United States, 90403
      • Recruiting
      • Sarcoma Oncology Center
      • Principal Investigator: Sant Chawla, MD
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Recruiting
      • Florida Cancer Specialists and Research Institute
      • Principal Investigator: Alexander Philipovskiy, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Principal Investigator: Sunandana Chandra, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Principal Investigator: Elizabeth Buchbinder, MD
  • New York
    • East Syracuse, New York, United States, 13057
      • Recruiting
      • Hematology Oncology Associates of Central New York
      • Principal Investigator: Steven Duffy, MD
    • New York, New York, United States, 10021
      • Recruiting
      • Weill Cornell Medicine
      • Principal Investigator: Anna Pavlick, DO
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Not yet recruiting
      • Duke University Cancer Institute
      • Principal Investigator: Jeffrey Clarke, MD
  • Tennessee
    • Nashville, Tennessee, United States, 27203
      • Recruiting
      • SCRI Oncology Partners
      • Principal Investigator: Melissa Johnson, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Principal Investigator: Shubham Pant, MD
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology
      • Principal Investigator: David Sommerhalder, MD
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology
      • Principal Investigator: Alex Spira, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: IMM-1-104 + mFFX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Dose (RP2D) candidate	Selection of candidate RP2D 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104	Cmax	After 12 weeks (3 Cycles) of study treatment
Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104	Tmax	After 12 weeks (3 Cycles) of study treatment
Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104	AUC0-t	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	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.	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.	Up to approximately 2 years.
Phase 2a: Landmark 3-Month Survival	The proportion of participants who are still alive after three months on study.	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.	After 6 months of study participation.
Phase 2a: Overall Survival (OS)	The time interval between study treatment start and death due to any cause.	Up to approximately 2 Years

Collaborators and Investigators

• Sponsor: Immuneering Corporation
• Investigators: Study Director: Vinny Hayreh, MD, Immuneering Corporation

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 14, 2022
• First Submitted That Met QC Criteria: October 14, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Estimated): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Adenocarcinoma; Advanced cancer; Targeted therapy; Metastatic cancer; KRAS; NRAS; MEK; RAS; HRAS; pan-RAS; Dual MEK; MEK 1/2; Mitogen-Activated Protein Kinase (MAPK); G12V; G12C; G12D; G12A; G12F; G12R; G12S; G13C; G13D; G13R; Q61H; Q61K; Q61L; Q61R; A146T; A146V; K117N
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Adenocarcinoma; Melanoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Folfirinox; Gemcitabine
• Other Study ID Numbers: IMM1104-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No