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

Официальное название

A Phase 1/1b Study of IAM1363 in Participants With Advanced Cancers Harboring HER2 Alterations

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат IAM1363
  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

Первичные конечные точки

• Incidence and severity of dose limiting toxicities (DLTs) (Part 1 only) [Срок оценки: 21 days]
• Incidence and severity of adverse events (AEs) [Срок оценки: Through 30 days after the last dose of study drug]
• Pharmacokinetic (PK) parameters [Срок оценки: Up to 42 days]
• Confirmed objective response rate (cORR) [Срок оценки: Through study completion, estimated as 46 months]
• Confirmed central nervous system ORR (CNS-cORR) [Срок оценки: Through study completion, estimated as 46 months]
• Frequency of IAM1363 dose modifications, including treatment discontinuations [Срок оценки: Through 30 days after the last dose of study drug]
• Incidence and severity of clinical laboratory abnormalities [Срок оценки: Through 30 days post last dose of study drug]
• Incidence of ECG abnormalities [Срок оценки: Through 30 days after the last dose of study drug]

Вторичные конечные точки (6)

• Best overall response (BoR) rate [Срок оценки: Through study completion, estimated as 46 months]
• Duration of response (DoR) [Срок оценки: Through study completion, estimated as 46 months]
• Disease control rate (DCR) [Срок оценки: Through study completion, estimated as 46 months]
• Clinical benefit rate (CBR) [Срок оценки: Through study completion, estimated as 46 months]
• Progression-free survival (PFS) [Срок оценки: Through study completion, estimated as 46 months]
• Overall survival (OS) [Срок оценки: Through study completion, estimated as 46 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 29 центров

• UCSD Moores Cancer Center — La Jolla
• USC Norris Comprehensive Cancer Center — Los Angeles
• University of Colorado Cancer Center — Aurora
• University of Miami — Miami
• Comprehensive Hematology Oncology — St. Petersburg
• University of Chicago — Chicago
• Massachusetts General Hospital — Boston
• Dana Farber Cancer Institute — Boston
• … и ещё 21 центр

Испания · 6 центров

• Hospital Universitario Vall dHebron — Barcelona
• Hospital Universitario 12 de Octubre — Madrid
• START Madrid CIOCC, Hospital Universitario HM Sanchinarro — Madrid
• Hospital Universitario Regional Málaga — Málaga
• Hospital Universitario Virgen del Rocio — Seville
• Hospital Clinico Universitario de Valencia (INCLIVA) — Valencia

Италия · 4 центра

• Azienda Ospedaliero Universitaria Careggi - Largo Giovanni Alessandro Brambilla 3 — Florence
• Istituto Europeo di Oncologia (IEO) — Milan
• Grande Ospedale Metropolitano Niguarda — Milan
• Azienda Ospedaliera Universitaria Luigi Vanvitelli — Naples

South Korea · 4 центра

• Seoul National University Hospital — Seoul
• Severance Hospital - Yonsei Cancer Center — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul

Франция · 3 центра

• Centre Georges François Leclerc — Dijon
• Institut de Cancerologie de l'Ouest — Saint-Herblain
• Institut Universitaire du Cancer de Toulouse (IUCT) Oncopole Institut Claudius Regaud " — Toulouse

Ирландия · 3 центра

• The START center Dublin — Dublin
• Cork University Hospital, Wilton — Cork
• St. Vincent's University Hospital — Dublin

Великобритания · 3 центра

• Royal Marsden NHS Foundation Trust, Royal Marsden Hospital (RMH)/Chelsea) — Chelsea
• Oxford University Hospitals NHS Foundation Trust Churchill Hospital — Oxford
• Royal Marsden NHS Foundation Trust, Royal Marsden Hospital (RMH)/Sutton — Sutton

Нидерланды · 1 центр

• Netherlands Cancer Institute-Antoni van Leeuwenhoek — Amsterdam

Идентификаторы

NCT: NCT06253871 · IAM1363-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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