Ireland
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Active, not recruiting Phase 1/2

A Phase 1/2a Study of IMM-1-104 in Participants With Advanced or Metastatic Solid Tumors

NCT05585320 · tracked via the Priya Life Science USA tracker
Phase
Phase 1/2
Started
2022-10-31
Last updated
2026-10-20

Condition(s) studied

Advanced Solid TumorPancreatic AdenocarcinomaMalignant Melanoma (Cutaneous)Non-small Cell Lung Cancer (NSCLC)

Investigational drug(s) / intervention(s)

IMM-1-104 Monotherapy (Treatment Group A)IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B)IMM-1-104 + modified FOLFIRINOX (Treatment Group C) →IMM-1-104 + dabrafenib (Treatment Group D) →IMM-1-104 + pembrolizumab (Treatment Group E) →

IMM-1-104 Monotherapy (Treatment Group A): Once-daily, oral IMM-1-104 dose administered in 28-day cycles until treatment discontinuation criteria are met

IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B): Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of gemcitabine and nab-paclitaxel until treatment discontinuation criteria are met. Gemcitabine will be administered at a dose of 1000 mg/m\^2 nab-Paclitaxel will be administered at a dose of 125 mg/m\^2

IMM-1-104 + modified FOLFIRINOX (Treatment Group C): Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of modified FOLFIRNOX until treatment discontinuation criteria are met. FOLFIRINOX will be administered as follows: Folinic Acid will be administered at 400 mg/m\^2 Fluorouracil will be administered at 2400 mg/m\^2 Irinotecan will be administered at 150 mg/m\^2 Oxaliplatin will be administered at 85 mg/m\^2

IMM-1-104 + dabrafenib (Treatment Group D): Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with twice daily oral dose of dabrafenib until treatment discontinuation criteria are met. Dabrafenib will be administered at a dose of 150mg daily (75mg twice daily).

IMM-1-104 + pembrolizumab (Treatment Group E): Once-daily, oral IMM-1-104 dose administered in 28-day cycles in combination with intravenous infusions of pembrolizumab in sequence or concurrently depending on the enrolled cohort (two sub cohorts) until treatment discontinuation criteria are met. Pembrolizumab will be administered at a dose of 400mg.

Study 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

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 outcome measure(s)

  • Phase 1: Adverse Events — From treatment initiation through 30 days following the last IMM-1-104 dose
    Number of participants with adverse events
  • Phase 1: Dose-Limiting Toxicities — The first 21 days of study treatment
    Number of participants with dose-limiting toxicities
  • Phase 1: Recommended Phase 2 Candidate Optimal Dose — Initiation of study treatment through 21 days (up to approximately 18 months)
    Selection of candidate optimal dose to take forward into Ph2a
  • Phase 2a: Overall Response Rate — After up to 48 weeks (12 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

Trial sites (20)

FacilityCityRegionStatus
Mayo Clinic Scottsdale Arizona
City of Hope Duarte California
University of California San Diego San Diego California
Sarcoma Oncology Center Santa Monica California
Sarah Cannon Research Institute Denver Colorado
Mayo Clinic Jacksonville Florida
Florida Cancer Specialists and Research Institute Lake Mary Florida
Northwestern University Chicago Illinois
University of Chicago Chicago Illinois
Dana Farber Cancer Institute Boston Massachusetts
Mayo Clinic Rochester Minnesota
Hematology Oncology Associates of Central New York East Syracuse New York
Weill Cornell Medicine New York New York
Levine Cancer Center Charlotte North Carolina
Duke University Cancer Institute Durham North Carolina
SCRI Oncology Partners Nashville Tennessee
MD Anderson Cancer Center Houston Texas
NEXT Oncology San Antonio Texas
NEXT Oncology Fairfax Virginia
University of Wisconsin Clinical Science Center Madison Wisconsin
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05585320 on ClinicalTrials.gov ↗ ← All trials in the USA