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

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

NCT ID: NCT06208124

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

Conditions: Official terms:
Melanoma
Adenocarcinoma

Conditions: 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

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: IMM-6-415
Description: Twice daily, oral tablet administered in 21-day cycles until treatment discontinuation criteria are met.
Arm group label: IMM-6-415

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.

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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Honor Health Research Institute

Address:
City: Scottsdale
Zip: 85258
Country: United States

Status: Recruiting

Investigator:
Last name: Muhammad Khawaja, MD
Email: Principal Investigator

Facility:
Name: City of Hope

Address:
City: Duarte
Zip: 91010
Country: United States

Status: Recruiting

Investigator:
Last name: Vincent Chung, MD
Email: Principal Investigator

Facility:
Name: Sarah Cannon Research Institute

Address:
City: Denver
Zip: 80218
Country: United States

Status: Recruiting

Investigator:
Last name: Jason Henry, MD
Email: Principal Investigator

Facility:
Name: Massachusetts General Hospital

Address:
City: Boston
Zip: 02114
Country: United States

Status: Recruiting

Investigator:
Last name: Ryan Sullivan, MD
Email: Principal Investigator

Facility:
Name: MD Anderson Cancer Center

Address:
City: Houston
Zip: 77030
Country: United States

Status: Recruiting

Investigator:
Last name: Jordi Rodon, MD
Email: Principal Investigator

Start date: February 27, 2024

Completion date: July 2027

Lead sponsor:
Agency: Immuneering Corporation
Agency class: Industry

Source: Immuneering Corporation

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06208124