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

Phase 1

Recruiting

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

• Registration Number: NCT05585320
• Lead Sponsor: Immuneering Corporation

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-10-14
• Study First Submitted QC: 2022-10-14
• Study First Posted: 2022-10-18
• Study Start: 2022-10-31
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-20
• Last Update Posted: 2024-08-21
• Primary Completion: 2026-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 210

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IMM-1-104 monotherapy (Treatment Group A)	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
IMM-1-104 in combination with mGnP (Treatment Group B)	IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B)	IMM-1-104 in combination with modified gemcitabine and nab-paclitaxel (mGnP) for first line pancreatic adenocarcinoma
IMM-1-104 in combination with mFFX (Treatment Group C)	IMM-1-104 + modified FOLFIRINOX (Treatment Group C)	IMM-1-104 in combination with modified FOLFIRINOX (mFFX) for first line pancreatic adenocarcinoma

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104	After 12 weeks (3 Cycles) of study treatment	Cmax
Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104	After 12 weeks (3 Cycles) of study treatment	Tmax
Phase 2a: Landmark 3-Month Survival	After 3 months of study participation.	The proportion of participants who are still alive after three months on study.
Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104	After 12 weeks (3 Cycles) of study treatment	AUC0-t
Phase 2a: Disease Control Rate (DCR)	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
Phase 2a: Progression Free Survival (PFS)	Up to approximately 2 years	The time interval between study treatment start and disease progression or death due to any cause.
Phase 2a: Duration of Response (DOR)	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.
Phase 2a: Landmark 6-Month Survival	After 6 months of study participation.	The proportion of participants who are still alive after six months on study.
Phase 2a: Overall Survival (OS)	Up to approximately 2 Years	The time interval between study treatment start and death due to any cause.

Trial Locations

Locations (15)

NEXT Oncology; 🇺🇸 Fairfax, Virginia, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of California San Diego; 🇺🇸 San Diego, California, United States

City of Hope; 🇺🇸 Duarte, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Sarcoma Oncology Center; 🇺🇸 Santa Monica, California, United States

Hematology Oncology Associates of Central New York; 🇺🇸 East Syracuse, New York, United States

Weill Cornell Medicine; 🇺🇸 New York, New York, United States

University of Wisconsin Clinical Science Center; 🇺🇸 Madison, Wisconsin, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Florida Cancer Specialists and Research Institute; 🇺🇸 Lake Mary, Florida, United States

Sarah Cannon Research Institute; 🇺🇸 Denver, Colorado, United States

Duke University Cancer Institute; 🇺🇸 Durham, North Carolina, United States

SCRI Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States