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

Phase 1RecruitingNCT06253871

Iambic Therapeutics, Inc383 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 4 parts: * Part 1 (Monotherapy Dose Escalation) * Part 2 (Dose Optimization) * Part 3 (Dose Expansion) * Part 4 (Combination Cohorts) 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). Part 4 will enroll 4 cohorts of participants who will receive IAM1363 in combination with other anti-cancer agents.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

383

Conditions

HER2 Mutation-Related Tumors

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Age ≥ 18 years * Have relapsed/refractory HER2-altered malignancy; for selected cohorts, prospective confirmation of HER2 alteration by central testing is required * 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% * Able to swallow oral medication Key Exclusion Criteria: * Clinically significant cardiac disease * Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: Participants 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 * Prior history of non-infectious interstitial lung disease (ILD). (Exceptions: participants with prior grade 1 ILD that has completely resolved are eligible) * Participants requiring immediate local therapy for brain metastases

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)

Incidence of treatment emergent AEs (TEAEs) and serious adverse events (SAEs)

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

Pharmacokinetic (PK) parameters

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

Time frame: Up to 42 days

Confirmed objective response rate (cORR)

Percentage of participants 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)

Percentage of participants 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

Frequency of IAM1363 dose modifications, including treatment discontinuations

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

Incidence and severity of clinical laboratory abnormalities

Time frame: Through 30 days post last dose of study drug

Incidence of ECG abnormalities

As measured using standard ECG parameters, including pulse rate, QT intervals, and QRS duration.

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

Secondary Outcomes

Best overall response (BoR) rate

BoR defined as the best response per RECIST v1.1 and RANO-BM 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 RANO-BM and date of disease progression per RECIST v1.1 and RANO-BM 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 and RANO-BM

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 and RANO-BM consecutively for 3 months

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 and RANO-BM or death without prior progression

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

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

Overview

Conditions

Interventions

Eligibility

Locations (48)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts