Brain Metastases From HER2 and Breast Cancer, Brain Metastases From Solid Tumors, CNS Metastases, HER2, HER2 + Breast Cancer, HER2 + Gastric Cancer, HER2 Mutation-Related Tumors, HER2-positive Bladder Cancer, HER2-positive Breast Cancer, HER2-positive Colorectal Cancer, HER2-positive Gastroesophageal Cancer, HER2-Positive Solid Tumors, NSCLC (Non-small Cell Lung Cancer)
Conditions
Keywords
ERBB2 protein, human, Molecular Targeted Therapy, Genes, erbB-2, Receptor, ErbB-2 / antagonists & inhibitors, Neoplasms / drug therapy, HER2 positive, HER2 overexpressing, HER2 altered, Human epidermal growth factor receptor, ErbB Receptors, HER2, brain metastases
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 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.
Interventions
DRUGIAM1363
IAM1363 monotherapy OR IAM1363 in combination with capecitabine + trastuzumab OR IAM1363 in combination with capecitabine + zanidatamab OR IAM1363 in combination with T-Dxd OR IAM1363 in combination with pembrolizumab +/- carboplatin and pemetrexed
Sponsors
Iambic Therapeutics, Inc
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose-escalation and dose optimization
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Through 30 days after the last dose of study drug | Incidence of treatment emergent AEs (TEAEs) and serious adverse events (SAEs) |
| Pharmacokinetic (PK) parameters | Up to 42 days | PK parameters. Includes but is not limited to assessment of maximum concentration (Cmax). |
| Confirmed objective response rate (cORR) | Through study completion, estimated as 46 months | Percentage of participants 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) | Through study completion, estimated as 46 months | Percentage of participants who achieve a confirmed CNS-cORR (CNS-CR + CNS-PR) per the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria |
| Frequency of IAM1363 dose modifications, including treatment discontinuations | Through 30 days after the last dose of study drug | — |
| Incidence and severity of clinical laboratory abnormalities | Through 30 days post last dose of study drug | — |
| Incidence of ECG abnormalities | Through 30 days after the last dose of study drug | As measured using standard ECG parameters, including pulse rate, QT intervals, and QRS duration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best overall response (BoR) rate | Through study completion, estimated as 46 months | BoR defined as the best response per RECIST v1.1 and RANO-BM 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 RANO-BM and date of disease progression per RECIST v1.1 and RANO-BM 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 and RANO-BM |
| 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 and RANO-BM consecutively for 3 months |
| 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 and RANO-BM 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 |
Countries
France, Ireland, Italy, Netherlands, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTIambic Therapeutics, Inc., Senior Medical Director
STUDY_DIRECTORIambic Therapeutics, Inc., Senior Medical Director
Iambic Therapeutics, Inc
Outcome results
None listed