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

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.

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