A Phase 1/1b Study of IAM1363 in HER2 Cancers

Phase 1RecruitingNCT06253871

Iambic Therapeutics, Inc243 enrolled

Overview

This is a Phase 1/1b open-label, multi-center dose escalation and dose optimization study designed to evaluate the safety and preliminary efficacy of IAM1363 in participants with advanced cancers that harbor HER2 alterations.

This is a Phase 1/1b open-label, multi-center study, designed to evaluate IAM1363 in participants with advanced cancers that harbor HER2 alterations. This study consists of the following 3 parts, which are described in further detail below: * Part 1 (Monotherapy Dose Escalation) * Part 2 (Dose Optimization) * Part 3 (Simon 2-Stage Evaluation) Part 1 will enroll participants with a confirmed, relapsed/refractory malignancy with documented diagnosis of HER2 alterations including participants with brain metastases. Once a provisional maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) has been determined, Part 2 will enroll additional cohorts to optimize dose selection and to further evaluate the safety and preliminary efficacy of IAM1363. Following completion of Dose Optimization, Part 3 will be opened to enroll tumor-specific cohorts utilizing a Simon 2-Stage Minimax Design to evaluate IAM1363 at the selected dose(s).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

243

Conditions

HER2 Mutation-Related Tumors HER2

Interventions

IAM1363DRUG

Oral, immediate release capsules of IAM1363

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Age ≥ 18 years * Have relapsed/refractory HER2-altered malignancy * Have progression of disease after the last systemic therapy, or be intolerant of last systemic therapy * Have radiographically measurable disease by RECIST v1.1 and/or RANO-BM * Eastern Cooperative Oncology Group (ECOG) performance score 0-1 * Have adequate baseline hematologic, liver and renal function * Have left ventricular ejection fraction (LVEF) ≥ 50% Key Exclusion Criteria: * Clinically significant cardiac disease * Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: Patients with well-controlled HIV (e.g., CD4 \>350/mm3 and undetectable viral load) are eligible * Current active liver disease including hepatitis A, hepatitis B , or hepatitis C * Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate absorption * Uncontrolled diabetes * History of solid organ transplantation * History of Grade ≥2 CNS hemorrhage, or any CNS hemorrhage within 28 days before C1D1 * Patients requiring immediate local therapy for brain metastases

Locations (45)

UCSD Moores Cancer Center

La Jolla, California, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, United States

RECRUITING

University of Miami

Miami, Florida, United States

Outcomes

Primary Outcomes

Incidence and severity of dose limiting toxicities (DLTs) (Part 1 only)

Incidence and severity of DLTs during the first cycle of treatment in participants in Part 1

Time frame: 21 days

Incidence and severity of adverse events (AEs) (Parts 1 and 2 only)

Incidence of treatment emergent AEs (TEAEs) and serious adverse events (SAEs) in participants in Parts 1 and 2

Time frame: Through 30 days after the last dose of study drug

Pharmacokinetic (PK) parameters (Parts 1 and 2 only)

PK parameters in participants in Parts 1 and 2. Includes but is not limited to assessment of maximum concentration (Cmax).

Time frame: Up to 42 days

Pharmacokinetic (PK) parameters (Parts 1 and 2 only)

PK parameters in participants in Parts 1 and 2. Includes but is not limited to assessment of time to maximum concentration (Tmax).

Time frame: Up to 42 days

Pharmacokinetic (PK) parameters (Parts 1 and 2 only)

PK parameters in participants in Parts 1 and 2. Includes but is not limited to assessment of area under the curve (AUC).

Time frame: Up to 42 days

Confirmed objective response rate (cORR) (Part 3 only)

Percentage of participants in Part 3 who achieve a confirmed objective response (complete response \[CR\] + partial response \[PR\]) per the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

Time frame: Through study completion, estimated as 46 months

Confirmed central nervous system ORR (CNS-cORR) (Part 3 Only)

Percentage of participants in Part 3 who achieve a confirmed CNS-cORR (CNS-CR + CNS-PR) per the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria

Time frame: Through study completion, estimated as 46 months

Secondary Outcomes

Incidence and severity of clinical laboratory abnormalities

Time frame: Through 30 days after the last dose of study drug

Incidence of electrocardiogram (ECG) abnormalities

Incidence of ECG abnormalities, as measured using standard ECG parameters, including respiratory rate, pulse rate, QT intervals, and QRS duration.

Time frame: Through 30 days after the last dose of study drug

cORR (Parts 1 and 2 only)

Percentage of participants in Parts 1 and 2 with cORR (CR + PR) per RECIST v1.1

Time frame: Through study completion, estimated as 46 months

Best overall response (BoR) rate

BoR defined as the best response per RECIST v1.1 across all assessments

Time frame: Through study completion, estimated as 46 months

Duration of response (DoR)

DoR defined as the time between the first confirmed objective response per RECIST v1.1 and date of disease progression per RECIST v1.1 or death due to any cause

Time frame: Through study completion, estimated as 46 months

Disease control rate (DCR)

DCR defined as the percentage of participants who achieve CR or PR, or stable disease (SD) per RECIST v1.1 consecutively for 3 months

Time frame: Through study completion, estimated as 46 months

Clinical benefit rate (CBR)

CBR defined as the percentage of participants who achieve CR, PR, or SD per RECIST v1.1

Time frame: Through study completion, estimated as 46 months

Progression-free survival (PFS)

PFS defined as the number of months from the date of first study treatment administration to the earliest of documented progressive disease per RECIST v1.1 or death without prior progression

Central Contacts

Iambic Therapeutics, Inc., Senior Medical Director

CONTACT

619-330-5499 ClinicalTrials@Iambic.ai

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Comprehensive Hematology Oncology

St. Petersburg, Florida, United States

RECRUITING

University of Chicago

Chicago, Illinois, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

RECRUITING

Henry Ford Cancer Institute

Detroit, Michigan, United States

RECRUITING

START - Midwest Cancer Research Center

Grand Rapids, Michigan, United States

RECRUITING

...and 35 more locations

Time frame: Through study completion, estimated as 46 months

Overall survival (OS)

OS defined as the number of months from the date of first study treatment administration to the date of death, irrespective of cause

Time frame: Through study completion, estimated as 46 months

Incidence and severity of AEs (Part 3 Only)

Incidence and severity of treatment emergent AEs and SAEs in participants in Part 3

Time frame: Through 30 days after the last dose of study drug

PK parameters (Part 3 only)

PK parameters in participants in Part 3. Includes but is not limited to assessment of maximum concentration (Cmax).

Time frame: Up to 42 days

PK parameters (Part 3 only)

PK parameters in participants in Part 3. Includes but is not limited to assessment of time to maximum concentration (Tmax).

Time frame: Up to 42 days

PK parameters (Part 3 only)

PK parameters in participants in Part 3. Includes but is not limited to assessment of area under the curve (AUC).

Time frame: Up to 42 days

Anti-tumor activity against CNS/brain metastases

Anti-tumor response based on RANO-BM Criteria

Time frame: Through study completion, estimated as 46 months