A Study of IMM-6-415 in RAS/RAF Mutant Solid Tumors

A Phase 1/2a Study of IMM-6-415 in Participants With Advanced or Metastatic Malignancies Harboring RAS or RAF Oncogenic Mutations

This is a FIH, ascending dose study to characterize the safety, tolerability, optimal dose and preliminary anti-tumor activity of IMM-6-415 in participants with advanced or metastatic solid tumors harboring RAS or RAF oncogenic mutations.

Study Overview

• Status: Completed
• Conditions: Pancreas Adenocarcinoma; Non-small Cell Lung Cancer; Advanced Solid Tumor (Phase 1); Malignant Melanoma (Cutaneous)
• Intervention / Treatment: Drug: IMM-6-415

Detailed Description

The dose exploration will identify the candidate recommended Phase 2 dose (RP2D) of IMM-6-415 to further explore the anti-tumor activity of IMM-6-415 as monotherapy in Phase 2a tumor-specific cohorts. Patients will be self-administering IMM-6-415 on a daily basis for up to 16 cycles (21-day cycles). During the first 2 cycles, PK and PD will be assessed. Solid tumor types with RAS/RAF mutations are eligible.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honor Health Research Institute
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Life expectancy >16 weeks
• Part 1: Histologically or cytologically confirmed diagnosis of a locally advanced unresectable or metastatic solid tumor malignancy harboring RAS (NRAS, KRAS, or HRAS)- or RAF- (ARAF, BRAF, RAF1) activating mutations, as documented by genomic analysis. Results of mutation analysis must be available prior to participant enrollment. A prior genomics report from archival tissues or liquid biopsy demonstrating mutation is acceptable
• Part 2: Histologically or cytologically confirmed diagnosis of one of the following locally advanced unresectable or metastatic solid tumor malignancies: pancreatic adenocarcinoma, RASmut melanoma, Class I BRAFmut melanoma, RASmut NSCLC, other RASmut GI cancers (aside from CRC) or any other RAFmut solid tumor as documented by genomic analysis. Results of mutation analysis must be available prior to participant enrollment. A prior genomics report from archival tissues or liquid biopsy demonstrating mutation is acceptable
• Participants must have received at least 1 line of systemic standard-of-care treatment for their advanced or metastatic disease and in the assessment of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from other treatment options
• Participants previously treated with codon-specific inhibitors of KRAS (including investigational agents) are eligible
• KRASG12C mutant participants must have received prior treatment with a KRASG12C inhibitor for any approved indication
• Radiologic evidence of measurable disease (i.e., at least 1 target lesion) according to RECIST 1.1 criteria
• ECOG performance status 0 or 1.
• Participant has adequate organ function

Exclusion Criteria:

• Inability to swallow oral medications.
• Symptomatic, untreated, or actively progressing known central nervous system metastases.
• Uncontrolled pleural or pericardial effusion or ascites requiring repeated drainage more than once every 28 days. In dwelling catheters are allowed.
• History of severe COVID-19 infection resulting in current need of supplemental O2 therapy to maintain resting oxygen saturations ≥90%.
• Presence of ongoing toxicities related to prior anticancer therapy that have not resolved to Grade ≤1 and are not otherwise allowed
• Impaired cardiac function or clinically significant cardiac disease
• Uncontrolled intercurrent illness including but not limited to poorly controlled diabetes or any medical condition determined by the Investigator to be a risk
• History or concurrent evidence of retinal vein occlusion (RVO) or current risk factors for RVO. History of clinically significant serous retinopathy, central serous chorioretinopathy or retinal edema.
• History of rhabdomyolysis within 3 months prior to Study Day 1
• HIV-infected participant must be on anti-retroviral therapy and have a well-controlled HIV infection/disease
• Participants with a history of HBV infection no longer requiring treatment are eligible; participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMM-6-415; Dose Escalation and Dose Expansion	Drug: IMM-6-415; Twice daily, oral tablet administered in 21-day cycles until treatment discontinuation criteria are met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 1/2a: Adverse Events	Number of participants with adverse events	From treatment initiation through 30 days following the last IMM-6-415 dose
Phase 1: Dose-Limiting Toxicities (DLT)	Number of participants with dose-limiting toxicities	The first 21 days of study treatment
Phase 1: Maximum Observed Plasma Concentration of IMM-6-415	Cmax	After 9 weeks (3 Cycles) of study treatment
Phase 1: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415	Tmax	After 9 weeks (3 Cycles) of study treatment
Phase 1: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415	AUC0-t	After 9 weeks (3 Cycles) of study treatment
Phase 1: Pharmacodynamic (PD) Activity of IMM-6-415 Plasma Concentrations Over Time	Surrogate PD Biomarker Assay, pERK	After 9 weeks (3 Cycles) of study treatment
Phase 2a: Overall Response Rate (ORR)	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 (16 cycles) of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: Maximum Observed Plasma Concentration of IMM-6-415	Cmax	After 9 weeks (3 Cycles) of study treatment
Phase 2a: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415	Tmax	After 9 weeks (3 Cycles) of study treatment
Phase 2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415	AUC0-t	After 9 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 12 weeks (4 Cycles) of study treatment
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): February 27, 2024
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: January 5, 2024
• First Submitted That Met QC Criteria: January 5, 2024
• First Posted (Actual): January 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: targeted therapy; adenocarcinoma; KRAS; BRAF; NRAS; MEK; RAS; RAF; HRAS; pan-RAS; Mitogen-Activated Protein Kinase (MAPK); G12V; V600E; pan-RAF; G12C; G12D; G12A; G12F; Q61H; Q61K; Q61L; Q61R; A146T; A146V; K117N; V600K; metastatic therapy; dual MEK
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Adenocarcinoma; Melanoma
• Other Study ID Numbers: IMM6415-101

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