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RecruitingInterventionalPhase 1

A Phase 1/1b Study of IAM1363 in Participants With Advanced Cancers Harboring HER2 Alterations

NCT ID: NCT06253871Sponsor: Iambic Therapeutics, IncLast updated: 2026-06-04

Summary

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.

Detailed description

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.

Arms & interventions

  • DrugIAM1363

    IAM1363 monotherapy OR IAM1363 in combination with capecitabine + trastuzumab OR IAM1363 in combination with capecitabine + zanidatamab OR IAM1363 in combination with T-Dxd OR IAM1363 in combination with pembrolizumab +/- carboplatin and pemetrexed

Outcome measures

Primary

  • 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

  • Best overall response (BoR) rate

    Time frame: Through study completion, estimated as 46 months

  • Duration of response (DoR)

    Time frame: Through study completion, estimated as 46 months

  • Disease control rate (DCR)

    Time frame: Through study completion, estimated as 46 months

  • Clinical benefit rate (CBR)

    Time frame: Through study completion, estimated as 46 months

  • Progression-free survival (PFS)

    Time frame: Through study completion, estimated as 46 months

  • Overall survival (OS)

    Time frame: Through study completion, estimated as 46 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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

Study locations (29)

UCSD Moores Cancer Center

La Jolla, California, 92093

Recruiting

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90089

Recruiting

University of Colorado Cancer Center

Aurora, Colorado, 80045

Recruiting

University of Miami

Miami, Florida, 33136

Recruiting

Comprehensive Hematology Oncology

St. Petersburg, Florida, 33709

Recruiting

University of Chicago

Chicago, Illinois, 60637

Recruiting

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

University of Michigan

Ann Arbor, Michigan, 48109

Recruiting

Henry Ford Cancer Institute

Detroit, Michigan, 48202

Recruiting

START - Midwest Cancer Research Center

Grand Rapids, Michigan, 49546

Recruiting

Saint Luke's Cancer Institute

Kansas City, Missouri, 64111

Recruiting

Washington University School of Medicine

St Louis, Missouri, 63110

Recruiting

Dartmouth Hitchcock Medical

Lebanon, New Hampshire, 03756

Recruiting

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901

Recruiting

Icahn School of Medicine at Mount Sinai

New York, New York, 10029

Recruiting

Duke Cancer Institute

Durham, North Carolina, 27710

Recruiting

University Hospital Cleveland Medical Center

Cleveland, Ohio, 44106

Recruiting

Cleveland Clinic

Cleveland, Ohio, 44195

Recruiting

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104

Recruiting

Providence Cancer Institute

Portland, Oregon, 97213

Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232

Recruiting

NEXT Oncology - Austin

Austin, Texas, 78758

Recruiting

Mary Crowley Cancer Research

Dallas, Texas, 75230

Recruiting

MD Anderson Cancer Center - University of Texas

Houston, Texas, 77030

Recruiting

START Mountain Region

West Valley City, Utah, 84119

Recruiting

NEXT Oncology - Virginia Cancer Specialists

Fairfax, Virginia, 22031

Recruiting

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

Recruiting