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

Phase 1

Recruiting

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

• Registration Number: NCT06208124
• Lead Sponsor: Immuneering Corporation

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.

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 Timeline

• Study First Submitted: 2024-01-05
• Study First Submitted QC: 2024-01-05
• Study First Posted: 2024-01-17
• Study Start: 2024-02-27
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-20
• Primary Completion: 2027-06
• Study Completion: 2027-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IMM-6-415	IMM-6-415	Dose Escalation and Dose Expansion

Primary Outcome Measures

Name	Time	Method
Phase 1: Dose-Limiting Toxicities (DLT)	The first 21 days of study treatment	Number of participants with dose-limiting toxicities
Phase 1: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415	After 9 weeks (3 Cycles) of study treatment	AUC0-t
Phase 1: Pharmacodynamic (PD) Activity of IMM-6-415 Plasma Concentrations Over Time	After 9 weeks (3 Cycles) of study treatment	Surrogate PD Biomarker Assay, pERK
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
Phase 1: Maximum Observed Plasma Concentration of IMM-6-415	After 9 weeks (3 Cycles) of study treatment	Cmax
Phase 1: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415	After 9 weeks (3 Cycles) of study treatment	Tmax
Phase 1/2a: Adverse Events	From treatment initiation through 30 days following the last IMM-6-415 dose	Number of participants with adverse events
Phase 2a: Overall Response Rate (ORR)	After up to 48 weeks (16 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

Secondary Outcome Measures

Name	Time	Method
Phase 2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415	After 9 weeks (3 Cycles) of study treatment	AUC0-t
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: 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: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415	After 9 weeks (3 Cycles) of study treatment	Tmax
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: Maximum Observed Plasma Concentration of IMM-6-415	After 9 weeks (3 Cycles) of study treatment	Cmax
Phase 2a: Overall Survival (OS)	Up to approximately 2 Years	The time interval between study treatment start and death due to any cause
Phase 2a: Disease Control Rate (DCR)	After 12 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: Landmark 3-Month Survival	After 3 months of study participation.	The proportion of participants who are still alive after three months on study

Trial Locations

Locations (5)

Honor Health Research Institute; 🇺🇸 Scottsdale, Arizona, United States

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

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

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

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