Overview
This is a Phase 1/1b open-label, multi-center dose escalation and dose optimization study, designed to evaluate safety and preliminary efficacy of IAM1363 as monotherapy and in combination with trastuzumab in patients with advanced cancers that harbor HER2 alterations.
Description
This is a Phase 1/1b open-label, multi-center study, designed to evaluate IAM1363 as monotherapy and in combination in patients 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) which consists of the following 2 subparts:
- Part 2a (Monotherapy Dose Optimization)
- Part 2b (Combination with Trastuzumab Dose Selection/Optimization)
- Part 3 (Simon 2-Stage Evaluation)
Part 1 will enroll patients with confirmed, relapsed/refractory malignancy with documented diagnosis of HER2 alterations including patients with brain metastases. Once a provisional MTD/RP2D is determined, Part 2 will enroll additional cohorts to optimize dose selection and to further evaluate the safety and preliminary efficacy of IAM1363 as monotherapy and in combination with trastuzumab. 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 as monotherapy or in combination with trastuzumab at the selected dose(s).
Eligibility
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 assessable by RECIST v1.1
- 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