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.
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.
Eligibility
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