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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06208124
• Other study ID #: IMM6415-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 27, 2024
• Est. completion date: July 2027

Study information

• Verified date: April 2024
• Source: Immuneering Corporation
• Contact: IMM-6-415 Study Team
• Phone: (860) 321-1302
• Email: clinicaltrials[@]immuneering.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: July 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Melanoma
• Non-small Cell Lung Cancer
• Pancreas Adenocarcinoma

Intervention

Drug:
• IMM-6-415
Twice daily, oral tablet administered in 21-day cycles until treatment discontinuation criteria are met.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Sarah Cannon Research Institute	Denver	Colorado
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Honor Health Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Immuneering Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1/2a: Adverse Events	Number of participants with adverse events	From treatment initiation through 30 days following the last IMM-6-415 dose
Primary	Phase 1: Dose-Limiting Toxicities (DLT)	Number of participants with dose-limiting toxicities	The first 21 days of study treatment
Primary	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)
Primary	Phase 1: Maximum Observed Plasma Concentration of IMM-6-415	Cmax	After 9 weeks (3 Cycles) of study treatment
Primary	Phase 1: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415	Tmax	After 9 weeks (3 Cycles) of study treatment
Primary	Phase 1: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415	AUC0-t	After 9 weeks (3 Cycles) of study treatment
Primary	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
Primary	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	Phase 2a: Maximum Observed Plasma Concentration of IMM-6-415	Cmax	After 9 weeks (3 Cycles) of study treatment
Secondary	Phase 2a: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415	Tmax	After 9 weeks (3 Cycles) of study treatment
Secondary	Phase 2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415	AUC0-t	After 9 weeks (3 Cycles) of study treatment
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	Phase 2a: Overall Survival (OS)	The time interval between study treatment start and death due to any cause	Up to approximately 2 Years