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

Sponsor

Immuneering Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05585320

Collaborator

(none)

156

Enrollment

Locations

Arm

Anticipated Duration (Months)

31.2

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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 in participants with RAS-mutated 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 in 4 Phase 2a tumor-specific cohorts.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor (Phase 1) Pancreatic Adenocarcinoma Malignant Melanoma (Cutaneous) Non-small Cell Lung Cancer (NSCLC) Colorectal Cancer (CRC)	Drug: IMM-1-104	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

156 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 31, 2022

Anticipated Primary Completion Date :

Jun 1, 2026

Anticipated Study Completion Date :

Jun 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IMM-1-104 Dose Escalation and Dose Expansion	Drug: IMM-1-104 Once-daily, oral tablet administered in 28-day cycles until treatment discontinuation criteria are met

Arm

Intervention/Treatment

Experimental: IMM-1-104

Dose Escalation and Dose Expansion

Drug: IMM-1-104

Once-daily, oral tablet administered in 28-day cycles until treatment discontinuation criteria are met

Outcome Measures

Primary Outcome Measures

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 Dose (RP2D) candidate [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 [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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must be ≥18 years of age
Phase 1: Must have histologically or cytologically confirmed RAS-mutated (KRAS, NRAS, or HRAS) solid tumor malignancy that is advanced and unresectable, or metastatic.
Phase 2a: Must have histologically or cytologically confirmed diagnosis of one of the following locally advanced unresectable or metastatic solid tumor malignancies: NRAS-mutant melanoma, KRAS-mutant pancreatic ductal adenocarcinoma (PDAC), KRAS-mutant non-small cell lung cancer (NSCLC), or KRAS-mutant and APC-wild-type colorectal cancer (CRC)
Must have received at least one prior systemic, standard-of-care therapy to treat 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Weill Cornell Medicine	New York	New York	United States	10021
3	MD Anderson Cancer Center	Houston	Texas	United States	77030
4	NEXT Oncology	San Antonio	Texas	United States	78229
5	NEXT Oncology	Fairfax	Virginia	United States	22031