Clinical trial NCT06253871: A Phase 1/1b Study of IAM1363 in HER2 Cancers
Official title: A Phase 1/1b Study of IAM1363 in Patients with Advanced Cancers Harboring HER2 Alterations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: HER2 Mutation-Related Tumors
HER2
HER2-positive Breast Cancer
HER2 + Breast Cancer
Brain Metastases from Solid Tumors
Brain Metastases from HER2 and Breast Cancer
CNS Metastases
HER2-Positive Solid Tumors
NSCLC (non-small Cell Lung Cancer)
HER2-positive Bladder Cancer
HER2-positive Colorectal Cancer
HER2 + Gastric Cancer
HER2-positive Gastroesophageal Cancer
Keywords: ERBB2 protein, human
Molecular Targeted Therapy
Genes, erbB-2
Receptor, ErbB-2 / antagonists &amp;amp; inhibitors
Neoplasms / drug therapy
HER2 positive
HER2 overexpressing
HER2 altered
Human epidermal growth factor receptor
ErbB Receptors
HER2
brain metastases
Lead sponsor: Iambic Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2024-02-12
Enrollment: 243
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Dose-escalation and dose optimization
Primary purpose: TREATMENT

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).

Eligibility criteria: 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 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 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

Primary outcomes:
measure: Incidence and severity of dose limiting toxicities (DLTs) (Part 1 only)
timeFrame: 21 days
measure: Incidence and severity of adverse events (AEs) (Parts 1 and 2 only)
timeFrame: Through 30 days after the last dose of study drug
measure: Pharmacokinetic (PK) parameters (Parts 1 and 2 only)
timeFrame: Up to 42 days
measure: Pharmacokinetic (PK) parameters (Parts 1 and 2 only)
timeFrame: Up to 42 days
measure: Pharmacokinetic (PK) parameters (Parts 1 and 2 only)
timeFrame: Up to 42 days
measure: Confirmed objective response rate (cORR) (Part 3 only)
timeFrame: Through study completion, estimated as 46 months
measure: Confirmed central nervous system ORR (CNS-cORR) (Part 3 Only)
timeFrame: Through study completion, estimated as 46 months
Secondary outcomes:
measure: Incidence and severity of clinical laboratory abnormalities
timeFrame: Through 30 days after the last dose of study drug
measure: Incidence of electrocardiogram (ECG) abnormalities
timeFrame: Through 30 days after the last dose of study drug
measure: cORR (Parts 1 and 2 only)
timeFrame: Through study completion, estimated as 46 months
measure: Best overall response (BoR) rate
timeFrame: Through study completion, estimated as 46 months
measure: Duration of response (DoR)
timeFrame: Through study completion, estimated as 46 months
measure: Disease control rate (DCR)
timeFrame: Through study completion, estimated as 46 months
measure: Clinical benefit rate (CBR)
timeFrame: Through study completion, estimated as 46 months
measure: Progression-free survival (PFS)
timeFrame: Through study completion, estimated as 46 months
measure: Overall survival (OS)
timeFrame: Through study completion, estimated as 46 months
measure: Incidence and severity of AEs (Part 3 Only)
timeFrame: Through 30 days after the last dose of study drug
measure: PK parameters (Part 3 only)
timeFrame: Up to 42 days
measure: PK parameters (Part 3 only)
timeFrame: Up to 42 days
measure: PK parameters (Part 3 only)
timeFrame: Up to 42 days
measure: Anti-tumor activity against CNS/brain metastases
timeFrame: Through study completion, estimated as 46 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Saint Petersburg
country: United States
facility: Comprehensive Hematology Oncology
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: START - Midwest Cancer Research Center
state: Michigan
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Austin
country: United States
facility: NEXT Oncology - Austin
state: Texas
city: Dallas
country: United States
facility: NEXT Oncology - Dallas
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Fairfax
country: United States
facility: NEXT Oncology - Virginia Cancer Specialists
state: Virginia
Study officials:
affiliation: Iambic Therapeutics, Inc
name: Iambic Therapeutics, Inc., Senior Medical Director
role: STUDY_DIRECTOR
References: