Clinical trial NCT06208124: A Study of IMM-6-415 in RAS/RAF Mutant Solid Tumors
Official title: A Phase 1/2a Study of IMM-6-415 in Participants With Advanced or Metastatic Malignancies Harboring RAS or RAF Oncogenic Mutations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Immuneering Corporation
Sponsor class: INDUSTRY
First posted: 2024-01-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Phase 1/2a: Adverse Events
timeFrame: From treatment initiation through 30 days following the last IMM-6-415 dose
measure: Phase 1: Dose-Limiting Toxicities (DLT)
timeFrame: The first 21 days of study treatment
measure: Phase 1: Recommended Phase 2 Dose (RP2D) candidate
timeFrame: Initiation of study treatment through 21 days (up to approximately 18 months)
measure: Phase 1: Maximum Observed Plasma Concentration of IMM-6-415
timeFrame: After 9 weeks (3 Cycles) of study treatment
measure: Phase 1: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415
timeFrame: After 9 weeks (3 Cycles) of study treatment
measure: Phase 1: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415
timeFrame: After 9 weeks (3 Cycles) of study treatment
measure: Phase 1: Pharmacodynamic (PD) Activity of IMM-6-415 Plasma Concentrations Over Time
timeFrame: After 9 weeks (3 Cycles) of study treatment
measure: Phase 2a: Overall Response Rate (ORR)
timeFrame: After up to 48 weeks (16 cycles) of study treatment
Secondary outcomes:
measure: Phase 2a: Maximum Observed Plasma Concentration of IMM-6-415
timeFrame: After 9 weeks (3 Cycles) of study treatment
measure: Phase 2a: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415
timeFrame: After 9 weeks (3 Cycles) of study treatment
measure: Phase 2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415
timeFrame: After 9 weeks (3 Cycles) of study treatment
measure: Phase 2a: Disease Control Rate (DCR)
timeFrame: After 12 weeks (4 Cycles) of study treatment
measure: Phase 2a: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Phase 2a: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Phase 2a: Landmark 3-Month Survival
timeFrame: After 3 months of study participation.
measure: Phase 2a: Landmark 6-Month Survival
timeFrame: After 6 months of study participation
measure: Phase 2a: Overall Survival (OS)
timeFrame: Up to approximately 2 Years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Immuneering Corporation
name: Vinny Hayreh, MD
role: STUDY_DIRECTOR
References: