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

Primary Purpose

Advanced Solid Tumor (Phase 1), Pancreatic Adenocarcinoma, Malignant Melanoma (Cutaneous)

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

IMM-1-104

About this trial

This is an interventional treatment trial for Advanced Solid Tumor (Phase 1) focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

City of HopeRecruiting
Weill Cornell MedicineRecruiting
MD Anderson Cancer CenterRecruiting
NEXT OncologyRecruiting
NEXT OncologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IMM-1-104

Arm Description

Dose Escalation and Dose Expansion

Outcomes

Primary Outcome Measures

Phase 1: Adverse Events

Number of participants with adverse events

Phase 1: Dose-Limiting Toxicities

Number of participants with dose-limiting toxicities

Phase 1: Recommended Phase 2 Dose (RP2D) candidate

Selection of candidate RP2D to take forward into Ph2a

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

Secondary Outcome Measures

Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104

Cmax

Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104

Tmax

Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104

AUC0-t

Phase 2a: Disease Control Rate (DCR)

The proportion of participants who have a best overall response (BOR) of stable disease (SD) or better

Phase 2a: Progression Free Survival (PFS)

The time interval between study treatment start and disease progression or death due to any cause.

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.

Phase 2a: Landmark 3-Month Survival

The proportion of participants who are still alive after three months on study.

Phase 2a: Landmark 6-Month Survival

The proportion of participants who are still alive after six months on study.

Phase 2a: Overall Survival (OS)

The time interval between study treatment start and death due to any cause.

Full Information

NCT ID

NCT05585320

First Posted

October 14, 2022

Last Updated

April 11, 2023

Sponsor

Immuneering Corporation

1. Study Identification

Unique Protocol Identification Number

NCT05585320

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 31, 2022 (Actual)

Primary Completion Date

June 2026 (Anticipated)

Study Completion Date

June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Immuneering Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Solid Tumor (Phase 1), Pancreatic Adenocarcinoma, Malignant Melanoma (Cutaneous), Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC)

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

156 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

IMM-1-104

Arm Type

Experimental

Arm Description

Dose Escalation and Dose Expansion

Intervention Type

Drug

Intervention Name(s)

IMM-1-104

Intervention Description

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

Primary Outcome Measure Information:

Title

Phase 1: Adverse Events

Description

Number of participants with adverse events

Time Frame

From treatment initiation through 30 days following the last IMM-1-104 dose

Title

Phase 1: Dose-Limiting Toxicities

Description

Number of participants with dose-limiting toxicities

Time Frame

The first 21 days of study treatment

Title

Phase 1: Recommended Phase 2 Dose (RP2D) candidate

Description

Selection of candidate RP2D to take forward into Ph2a

Time Frame

Initiation of study treatment through 21 days (up to approximately 18 months)

Title

Phase 2a: Overall Response Rate

Description

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

Time Frame

After up to 48 weeks (12 cycles) of study treatment

Secondary Outcome Measure Information:

Title

Phase 1/2a: Maximum Observed Plasma Concentration of IMM-1-104

Description

Cmax

Time Frame

After 12 weeks (3 Cycles) of study treatment

Title

Phase 1/2a: Time to Reach Maximum Plasma Concentration of IMM-1-104

Description

Tmax

Time Frame

After 12 weeks (3 Cycles) of study treatment

Title

Phase 1/2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-1-104

Description

AUC0-t

Time Frame

After 12 weeks (3 Cycles) of study treatment

Title

Phase 2a: Disease Control Rate (DCR)

Description

The proportion of participants who have a best overall response (BOR) of stable disease (SD) or better

Time Frame

After 16 weeks (4 Cycles) of study treatment

Title

Phase 2a: Progression Free Survival (PFS)

Description

The time interval between study treatment start and disease progression or death due to any cause.

Time Frame

Up to approximately 2 years

Title

Phase 2a: Duration of Response (DOR)

Description

The time interval between an assessment of partial response (PR) or better and disease progression or death due to any cause.

Time Frame

Up to approximately 2 years.

Title

Phase 2a: Landmark 3-Month Survival

Description

The proportion of participants who are still alive after three months on study.

Time Frame

After 3 months of study participation.

Title

Phase 2a: Landmark 6-Month Survival

Description

The proportion of participants who are still alive after six months on study.

Time Frame

After 6 months of study participation.

Title

Phase 2a: Overall Survival (OS)

Description

The time interval between study treatment start and death due to any cause.

Time Frame

Up to approximately 2 Years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

IMM1104-101 Study Team

Phone

(860) 321-1302

clinicaltrials@immuneering.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Scott Barrett, MD

Organizational Affiliation

Immuneering Corporation

Official's Role

Study Chair

Facility Information:

Facility Name

City of Hope

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Vincent Chung, MD

Facility Name

Weill Cornell Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anna Pavlick, DO

Facility Name

MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shubham Pant, MD

Facility Name

NEXT Oncology

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Sommerhalder, MD

Facility Name

NEXT Oncology

City

Fairfax

State/Province

Virginia

ZIP/Postal Code

22031

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alex Spira, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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