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

Immuneering Corporation

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B); Drug: IMM-1-104 + modified FOLFIRINOX (Treatment Group C); Drug: IMM-1-104 Monotherapy (Treatment Group A)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05585320

IMM1104-101

Details and patient eligibility

About

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.

Enrollment: 210 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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210 participants in 3 patient groups

IMM-1-104 monotherapy (Treatment Group A)

Experimental group

Description:

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

Treatment:

Drug: IMM-1-104 Monotherapy (Treatment Group A)

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

Experimental group

Description:

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

Treatment:

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

IMM-1-104 in combination with mFFX (Treatment Group C)

Experimental group

Description:

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

Treatment:

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