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

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05585320
• Other study ID #: IMM1104-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 31, 2022
• Est. completion date: June 2027

Study information

• Verified date: April 2024
• Source: Immuneering Corporation
• Contact: IMM1104-101 Study Team
• Phone: (860) 321-1302
• Email: clinicaltrials[@]immuneering.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: June 2027
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

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
• 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

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	Duke University Cancer Institute	Durham	North Carolina
United States	Hematology Oncology Associates of Central New York	East Syracuse	New York
United States	NEXT Oncology	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	Florida Cancer Specialists and Research Institute	Lake Mary	Florida
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Weill Cornell Medicine	New York	New York
United States	NEXT Oncology	San Antonio	Texas
United States	University of California San Diego	San Diego	California
United States	Sarcoma Oncology Center	Santa Monica	California

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: Adverse Events	Number of participants with adverse events	From treatment initiation through 30 days following the last IMM-1-104 dose
Primary	Phase 1: Dose-Limiting Toxicities	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 2a: Overall Response Rate	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 (12 cycles) of study treatment
Secondary	Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104	Cmax	After 12 weeks (3 Cycles) of study treatment
Secondary	Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104	Tmax	After 12 weeks (3 Cycles) of study treatment
Secondary	Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104	AUC0-t	After 12 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 16 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