Clinical trial NCT05585320: A Phase 1/2a Study of IMM-1-104 in Participants With Advanced or Metastatic Solid Tumors
Official title: A Phase 1/2a, Open-Label, Multicenter, Nonrandomized, Safety and Anti-tumor Activity Study of IMM-1-104, a Novel Oral Dual MEK1/2 Inhibitor in Participants With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Pancreatic Adenocarcinoma
Malignant Melanoma (Cutaneous)
Non-small Cell Lung Cancer (NSCLC)
Keywords: pan-RAS
KRAS
NRAS
HRAS
Targeted therapy
Metastatic cancer
Advanced cancer
RAS
Adenocarcinoma
MEK
Dual MEK
MEK 1/2
Mitogen-Activated Protein Kinase (MAPK)
G12A
G12C
G12D
G12F
G12R
G12S
G12V
G13C
G13D
G13R
Q61H
Q61K
Q61L
Q61R
A146T
A146V
K117N
Lead sponsor: Immuneering Corporation
Sponsor class: INDUSTRY
First posted: 2022-10-18
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, dose-exploration and expansion study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of IMM-1-104 when administered as monotherapy or in combination with approved agents in participants with RAS-mutated or RAS/MAPK activated advanced or metastatic solid tumors. The dose exploration will identify the candidate recommended Phase 2 candidate optimal dose of IMM-1-104 to further explore the anti-tumor activity of IMM-1-104 as monotherapy and in combination with approved agents in multiple Phase 2a proof-of-concept cohorts in malignancies of interest.


Eligibility criteria: Inclusion Criteria:

* Must be ≥18 years of age
* Must have histologically or cytologically confirmed diagnosis as follows:

  1. Monotherapy Phase 1: A locally advanced unresectable or metastatic solid tumor malignancy that harbors a RAS (KRAS, NRAS, or HRAS) activating mutation.
  2. Monotherapy Phase 2a: A locally advanced unresectable or metastatic solid tumor malignancies: pancreatic ductal adenocarcinoma (PDAC), RAS-mutant melanoma, or RAS-mutant non-small cell lung cancer (NSCLC)
  3. Combination therapy (both phases): A locally advanced unresectable or metastatic PDAC
  4. Combination therapy Phase 2a, Treatment D: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma with BRAF mutation. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb.
  5. Combination therapy Phase 2a, Treatment E: Second and third line participants with unresectable stage III or stage IV cutaneous melanoma. Must have progressed on or after treatment with an anti-PD-(L)1 monoclonal antibody as the most recent therapy. First day of study treatment must be more than 28 days but less than 12 weeks from the last dose of anti-PD-(L)1 mAb.
* Participants must be treatment naive or received prior systemic standard-of-care treatment as follows:

  1. Monotherapy Phase 1: received at least 1 line of systemic standard-of-care treatment for their advanced or metastatic disease
  2. Monotherapy Phase 2a:

     1. First-line PDAC participants will have received no previous systemic anti-cancer therapy. Second-line PDAC participants will have received no more than one prior systemic anti-cancer therapy.
     2. First-line melanoma participants will have received no previous systemic anti-cancer therapy. Second- and third-line participants will have received and failed one or two prior systemic anti-cancer therapies, respectively.
     3. NSCLC participants will have received at least one and no more than two previous lines of systemic therapy.
  3. Combination therapy (both phases): PDAC participants will have received no previous systemic anti-cancer therapy for their advanced or metastatic disease.
* Must have evidence of measurable disease (at least one target lesion) per RECIST v1.1 criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate organ function

Exclusion Criteria:

* Inability to swallow oral medications
* Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases
* History or concurrent evidence of retinal vein occlusion (RVO) or current risk factors for RVO. History of serous retinopathy, retinal edema, or retinal pigment epithelial detachment (RPED)
* Impaired cardiovascular function or clinically significant cardiac disease
* History of rhabdomyolysis within 3 months prior to start of study treatment
* Active skin disorder requiring systemic treatment within 3 months prior to the start of study treatment
* Participants with active, uncontrolled autoimmune disease or participants actively being treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors for management of their autoimmune disease are excluded
* Receipt of an allogeneic tissue/solid organ transplant
* 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: Adverse Events
timeFrame: From treatment initiation through 30 days following the last IMM-1-104 dose
measure: Phase 1: Dose-Limiting Toxicities
timeFrame: The first 21 days of study treatment
measure: Phase 1: Recommended Phase 2 Candidate Optimal Dose
timeFrame: Initiation of study treatment through 21 days (up to approximately 18 months)
measure: Phase 2a: Overall Response Rate
timeFrame: After up to 48 weeks (12 cycles) of study treatment
Secondary outcomes:
measure: Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104
timeFrame: After 12 weeks (3 Cycles) of study treatment
measure: Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104
timeFrame: After 12 weeks (3 Cycles) of study treatment
measure: Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104
timeFrame: After 12 weeks (3 Cycles) of study treatment
measure: Phase 2a: Disease Control Rate (DCR)
timeFrame: After 16 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: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Lake Mary
country: United States
facility: Florida Cancer Specialists and Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Cancer Institute
state: North Carolina
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
Study officials:
affiliation: Immuneering Corporation
name: Vinny Hayreh, MD
role: STUDY_DIRECTOR
References: