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

NCT06208124 | Completed Phase 1 FDA Drug

• 1 other identifier: IMM6415-101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Advanced Solid Tumor (Phase 1); Pancreas Adenocarcinoma; Non-small Cell Lung Cancer; Malignant Melanoma (Cutaneous)

Keywords

pan-RAS; pan-RAF; KRAS; NRAS; HRAS; BRAF; targeted therapy; metastatic therapy; RAS; RAF; adenocarcinoma; MEK; dual MEK; G12A; G12C; G12D; G12F; G12V; Q61H; Q61K; Q61R; Q61L; A146T; A146V; K117N; Mitogen-Activated Protein Kinase (MAPK); V600E; V600K

Outcome Measures

Primary Outcomes (8)

• 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: 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: 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 Outcomes (9)

• Phase 2a: Maximum Observed Plasma Concentration of IMM-6-415

  After 9 weeks (3 Cycles) of study treatment

• Phase 2a: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415

  After 9 weeks (3 Cycles) of study treatment

• Phase 2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415

  After 9 weeks (3 Cycles) of study treatment

• Phase 2a: Disease Control Rate (DCR)

  After 12 weeks (4 Cycles) of study treatment

• Phase 2a: Progression Free Survival (PFS)

  Up to approximately 2 years

Study Arms (1)

IMM-6-415

EXPERIMENTAL

Dose Escalation and Dose Expansion

Drug: IMM-6-415

Interventions

IMM-6-415 DRUG

Twice daily, oral tablet administered in 21-day cycles until treatment discontinuation criteria are met.

IMM-6-415

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Immuneering Corporation: lead

Study Sites (5)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma, Cutaneous Malignant; Adenocarcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma; Neoplasms, Glandular and Epithelial

Study Officials

• Vinny Hayreh, MD

  Immuneering Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2024
• First Posted: January 17, 2024
• Study Start: February 27, 2024
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)