A Phase 1/1b Study of IAM1363 in HER2 Cancers
- Conditions
- HER2 Mutation-Related TumorsHER2HER2-positive Breast CancerHER2 + Breast CancerBrain Metastases from Solid TumorsBrain Metastases from HER2 and Breast CancerCNS MetastasesHER2-Positive Solid TumorsNSCLC (non-small Cell Lung Cancer)HER2-positive Bladder Cancer
- Interventions
- Registration Number
- NCT06253871
- Lead Sponsor
- Iambic Therapeutics, Inc
- Brief 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 3 parts, which are described in further detail below:
* Part 1 (Monotherapy Dose Escalation)
* Part 2 (Dose Optimization)
* Part 3 (Simon 2-Stage Evaluation)
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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 243
- 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 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%
Key
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description IAM1363 Monotherapy IAM1363 Treatment with IAM1363 capsules, dosed orally either once or twice daily in 21-day cycles.
- Primary Outcome Measures
Name Time Method Incidence and severity of dose limiting toxicities (DLTs) (Part 1 only) 21 days Incidence and severity of DLTs during the first cycle of treatment in participants in Part 1
Incidence and severity of adverse events (AEs) (Parts 1 and 2 only) Through 30 days after the last dose of study drug Incidence of treatment emergent AEs (TEAEs) and serious adverse events (SAEs) in participants in Parts 1 and 2
Pharmacokinetic (PK) parameters (Parts 1 and 2 only) Up to 42 days PK parameters in participants in Parts 1 and 2. Includes but is not limited to assessment of area under the curve (AUC).
Confirmed objective response rate (cORR) (Part 3 only) Through study completion, estimated as 46 months Percentage of participants in Part 3 who achieve a confirmed objective response (complete response \[CR\] + partial response \[PR\]) per the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Confirmed central nervous system ORR (CNS-cORR) (Part 3 Only) Through study completion, estimated as 46 months Percentage of participants in Part 3 who achieve a confirmed CNS-cORR (CNS-CR + CNS-PR) per the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria
- Secondary Outcome Measures
Name Time Method Incidence and severity of clinical laboratory abnormalities Through 30 days after the last dose of study drug Incidence and severity of clinical laboratory abnormalities
Incidence of electrocardiogram (ECG) abnormalities Through 30 days after the last dose of study drug Incidence of ECG abnormalities, as measured using standard ECG parameters, including respiratory rate, pulse rate, QT intervals, and QRS duration.
cORR (Parts 1 and 2 only) Through study completion, estimated as 46 months Percentage of participants in Parts 1 and 2 with cORR (CR + PR) per RECIST v1.1
Best overall response (BoR) rate Through study completion, estimated as 46 months BoR defined as the best response per RECIST v1.1 across all assessments
Duration of response (DoR) Through study completion, estimated as 46 months DoR defined as the time between the first confirmed objective response per RECIST v1.1 and date of disease progression per RECIST v1.1 or death due to any cause
Disease control rate (DCR) Through study completion, estimated as 46 months DCR defined as the percentage of participants who achieve CR or PR, or stable disease (SD) per RECIST v1.1 consecutively for 3 months
Clinical benefit rate (CBR) Through study completion, estimated as 46 months CBR defined as the percentage of participants who achieve CR, PR, or SD per RECIST v1.1
Progression-free survival (PFS) Through study completion, estimated as 46 months 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 or death without prior progression
Overall survival (OS) Through study completion, estimated as 46 months OS defined as the number of months from the date of first study treatment administration to the date of death, irrespective of cause
Incidence and severity of AEs (Part 3 Only) Through 30 days after the last dose of study drug Incidence and severity of treatment emergent AEs and SAEs in participants in Part 3
PK parameters (Part 3 only) Up to 42 days PK parameters in participants in Part 3. Includes but is not limited to assessment of area under the curve (AUC).
Anti-tumor activity against CNS/brain metastases Through study completion, estimated as 46 months Anti-tumor response based on RANO-BM Criteria
Trial Locations
- Locations (12)
Comprehensive Hematology Oncology
🇺🇸Saint Petersburg, Florida, United States
OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
START - Midwest Cancer Research Center
🇺🇸Grand Rapids, Michigan, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
NEXT Oncology - Austin
🇺🇸Austin, Texas, United States
NEXT Oncology - Dallas
🇺🇸Dallas, Texas, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
START Mountain Region
🇺🇸West Valley City, Utah, United States
NEXT Oncology - Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States