A Phase 1/2a Study of IMM-1-104 in Participants With Previously Treated, RAS-Mutant, Advanced or Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT05585320
• Recruitment Status: Recruiting
• First Posted: October 18, 2022
• Last Update Posted: May 20, 2024
• Sponsor: Immuneering Corporation
• Information provided by (Responsible Party): Immuneering Corporation

Tracking Information

• First Submitted Date: October 14, 2022
• First Posted Date: October 18, 2022
• Last Update Posted Date: May 20, 2024
• Actual Study Start Date: October 31, 2022
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 17, 2022)

• Phase 1: Adverse Events [ Time Frame: From treatment initiation through 30 days following the last IMM-1-104 dose ]
  Number of participants with adverse events
• Phase 1: Dose-Limiting Toxicities [ Time Frame: The first 21 days of study treatment ]
  Number of participants with dose-limiting toxicities
• Phase 1: Recommended Phase 2 Dose (RP2D) candidate [ Time Frame: Initiation of study treatment through 21 days (up to approximately 18 months) ]
  Selection of candidate RP2D to take forward into Ph2a
• Phase 2a: Overall Response Rate [ Time Frame: 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

Original Primary Outcome Measures (submitted: October 14, 2022)

• Phase 1: Adverse Events [ Time Frame: From treatment initiation through 30 days following the last IMM-1-104 dose ]
  Number of participants with adverse events
• Phase 1: Dose-Limiting Toxicities [ Time Frame: The first 21 days of study treatment ]
  Number of participants with dose-limiting toxicites
• Phase 1: Recommended Phase 2 Dose (RP2D) candidate [ Time Frame: Initiation of study treatment through 21 days (up to approximately 18 months) ]
  Selection of candidate RP2D to take forward into Ph2a
• Phase 2a: Overall response rate [ Time Frame: 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 critieria

Current Secondary Outcome Measures (submitted: October 17, 2022)

• Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104 [ Time Frame: After 12 weeks (3 Cycles) of study treatment ]
  Cmax
• Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104 [ Time Frame: After 12 weeks (3 Cycles) of study treatment ]
  Tmax
• Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104 [ Time Frame: After 12 weeks (3 Cycles) of study treatment ]
  AUC0-t
• Phase 2a: Disease Control Rate (DCR) [ Time Frame: After 16 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: Progression Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
  The time interval between study treatment start and disease progression or death due to any cause.
• Phase 2a: Duration of Response (DOR) [ Time Frame: 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: Landmark 3-Month Survival [ Time Frame: After 3 months of study participation. ]
  The proportion of participants who are still alive after three months on study.
• Phase 2a: Landmark 6-Month Survival [ Time Frame: After 6 months of study participation. ]
  The proportion of participants who are still alive after six months on study.
• Phase 2a: Overall Survival (OS) [ Time Frame: Up to approximately 2 Years ]
  The time interval between study treatment start and death due to any cause.

Original Secondary Outcome Measures (submitted: October 14, 2022)

• Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104 [ Time Frame: After 12 weeks (3 Cycles) of study treatment ]
  Cmax
• Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104 [ Time Frame: After 12 weeks (3 Cycles) of study treatment ]
  Tmax
• Phase 1/2a: Area Under Plasma Concentration Time Curve of IMM-1-104 [ Time Frame: After 12 weeks (3 Cycles) of study treatment ]
  AUC0-t
• Phase 2a: Disease Control Rate (DCR) [ Time Frame: After 16 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: Progression Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
  The time interval between study treatment start and disease progression or death due to any cause.
• Phase 2a: Duration of Response (DOR) [ Time Frame: 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: Landmark 3-Month Survival [ Time Frame: After 3 months of study participation. ]
  The proportion of participants who are still alive after three months on study.
• Phase 2a: Landmark 6-Month Survival [ Time Frame: After 6 months of study participation. ]
  The proportion of participants who are still alive after six months on study.
• Phase 2a: Overall Survival (OS) [ Time Frame: Up to approximately 2 Years ]
  The time interval between study treatment start and death due to any cause.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1/2a Study of IMM-1-104 in Participants With Previously Treated, RAS-Mutant, 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 Previously Treated RAS-Mutated Advanced or Metastatic Solid Tumors
• 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 dose (RP2D) 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Solid Tumor
• Pancreatic Adenocarcinoma
• Malignant Melanoma (Cutaneous)
• Non-small Cell Lung Cancer (NSCLC)

Intervention

• Drug: 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
  Other Name: IMM-1-104
• Drug: 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

  Other Name: IMM-1-104 + mGnP
• Drug: 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

  Other Name: IMM-1-104 + mFFX

Study Arms

• Experimental: IMM-1-104 monotherapy (Treatment Group A)
  IMM-1-104 monotherapy for first/second line pancreatic adenocarcinoma; first/second/third line melanoma; or second/third line non small cell lung cancer
  Intervention: Drug: IMM-1-104 Monotherapy (Treatment Group A)
• Experimental: IMM-1-104 in combination with mGnP (Treatment Group B)
  IMM-1-104 in combination with modified gemcitabine and nab-paclitaxel (mGnP) for first line pancreatic adenocarcinoma
  Intervention: Drug: IMM-1-104 + modified Gemcitabine/nab-Paclitaxel (Treatment Group B)
• Experimental: IMM-1-104 in combination with mFFX (Treatment Group C)
  IMM-1-104 in combination with modified FOLFIRINOX (mFFX) for first line pancreatic adenocarcinoma
  Intervention: Drug: IMM-1-104 + modified FOLFIRINOX (Treatment Group C)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 20, 2023): 210
• Original Estimated Enrollment (submitted: October 14, 2022): 156
• Estimated Study Completion Date: June 2027
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

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

• 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
• Females who are pregnant, breastfeeding, or planning to become pregnant and males who plan to father a child while enrolled in this study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: IMM1104-101 Study Team; (860) 321-1302; clinicaltrials@immuneering.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05585320
• Other Study ID Numbers: IMM1104-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Immuneering Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Immuneering Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Vinny Hayreh, MD; Immuneering Corporation

• PRS Account: Immuneering Corporation
• Verification Date: May 2024