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Recruiting NCT06253871

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

Phase I Interventional HER2 Mutation-Related Tumors HER2 HER2-positive Breast Cancer HER2 + Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: IAM1363.
Who it may be relevant to
Registry conditions: HER2 Mutation-Related Tumors, HER2, HER2-positive Breast Cancer, HER2 + Breast Cancer. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, France, Ireland, Italy, Netherlands +3
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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

  • Drug 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

Primary outcome measures

  • Incidence and severity of dose limiting toxicities (DLTs) (Part 1 only) [Time frame: 21 days]
  • Incidence and severity of adverse events (AEs) [Time frame: Through 30 days after the last dose of study drug]
  • Pharmacokinetic (PK) parameters [Time frame: Up to 42 days]
  • Confirmed objective response rate (cORR) [Time frame: Through study completion, estimated as 46 months]
  • Confirmed central nervous system ORR (CNS-cORR) [Time frame: Through study completion, estimated as 46 months]
  • Frequency of IAM1363 dose modifications, including treatment discontinuations [Time frame: Through 30 days after the last dose of study drug]
  • Incidence and severity of clinical laboratory abnormalities [Time frame: Through 30 days post last dose of study drug]
  • Incidence of ECG abnormalities [Time frame: Through 30 days after the last dose of study drug]
Secondary outcome measures (6)
  • Best overall response (BoR) rate [Time frame: Through study completion, estimated as 46 months]
  • Duration of response (DoR) [Time frame: Through study completion, estimated as 46 months]
  • Disease control rate (DCR) [Time frame: Through study completion, estimated as 46 months]
  • Clinical benefit rate (CBR) [Time frame: Through study completion, estimated as 46 months]
  • Progression-free survival (PFS) [Time frame: Through study completion, estimated as 46 months]
  • Overall survival (OS) [Time frame: Through study completion, estimated as 46 months]

Eligibility criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 29 centers
  • 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
  • … and 21 more centers
Spain · 6 centers
  • 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
Italy · 4 centers
  • 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 centers
  • Seoul National University Hospital — Seoul
  • Severance Hospital - Yonsei Cancer Center — Seoul
  • Asan Medical Center — Seoul
  • Samsung Medical Center — Seoul
France · 3 centers
  • 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
Ireland · 3 centers
  • The START center Dublin — Dublin
  • Cork University Hospital, Wilton — Cork
  • St. Vincent's University Hospital — Dublin
United Kingdom · 3 centers
  • 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
Netherlands · 1 center
  • Netherlands Cancer Institute-Antoni van Leeuwenhoek — Amsterdam

Identifiers

NCT: NCT06253871 · IAM1363-01

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗