Actively Recruiting

Phase 1
Phase 2
Age: 18Years +
All Genders
NCT06298084

Dose-Expansion Modular Study To Explore the Safety, Tolerability, and Anti-tumor Activity of HER3- DXd Monotherapy and Combinations in Patients With Inoperable Advanced Breast Cancer (ABC) After Progression on T-DXd

Led by Gustave Roussy, Cancer Campus, Grand Paris · Updated on 2024-03-29

152

Participants Needed

1

Research Sites

271 weeks

Total Duration

On this page

Sponsors

G

Gustave Roussy, Cancer Campus, Grand Paris

Lead Sponsor

D

Daiichi Sankyo

Collaborating Sponsor

AI-Summary

What this Trial Is About

ICARUS-BREAST02 is an open-label, multicenter, phase 1b/2, platform study that aims to evaluate the safety, tolerability, and efficacy of HER3-DXd monotherapy and in combination with other anti-cancer agents in patients with ABC. The first 2 modules will evaluate: i. safety and efficacy of HER3-DXd with olaparib in patients with HER2-low and HER2-positive ABC progressed on T-DXd (Module 1) and HER3-DXd monotherapy in patients with HER2-low ABC progressed on T-DXd (Module 0). The main objective of Part 1 is to assess the safety and tolerability of HER3-DXd monotherapy and combination and to determine the recommended phase 2 dose (RP2D) of the combination containing HER3-DXd. The main objective of Part 2 is to assess the efficacy of study therapies in each module based on investigator assessment as evaluated by the objective response rate (ORR) at 6 months.

CONDITIONS

Official Title

Dose-Expansion Modular Study To Explore the Safety, Tolerability, and Anti-tumor Activity of HER3- DXd Monotherapy and Combinations in Patients With Inoperable Advanced Breast Cancer (ABC) After Progression on T-DXd

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Patients must have progressed during or within 2 months after treatment with T-DXd
  • Patients with HER2-positive tumors must have prior treatment with trastuzumab and taxanes
  • Patients with HER2-low tumors must have been treated with taxanes
  • Patients with hormone receptor-positive tumors must have received endocrine therapy and CDK4/6 inhibitors
  • Patients with germline BRCA1/2 mutations must have received prior PARP inhibitor treatment
  • Adults aged 18 years or older
  • Histologically confirmed advanced or metastatic breast cancer not suitable for surgery
  • ECOG performance status of 0 or 1 at screening
  • HER2-positive or HER2-low tumors with any hormone receptor status before T-DXd treatment
  • At least one measurable lesion by RECIST v1.1 criteria or evaluable bone lesion with soft tissue component
  • Tumor site accessible for biopsy and patient agrees to biopsies before, during, and after treatment
  • Adequate bone marrow and organ function within 14 days before starting treatment
  • Female patients of childbearing potential must have a negative pregnancy test and agree to use effective contraception
  • Female patients must not donate or retrieve eggs during and for 8 months after treatment
  • Male patients must be surgically sterile or agree to use effective birth control during and for 5 months after treatment
  • Male patients must not donate or freeze sperm during and for 5 months after treatment
  • Ability and willingness to comply with study procedures and visits
  • Affiliation with a social security system or beneficiary status
Not Eligible

You will not qualify if you...

  • Breast cancer that can be treated with surgery or radiation with curative intent
  • History or evidence of interstitial lung disease or pulmonary fibrosis
  • Severe lung problems or autoimmune diseases affecting the lungs
  • Use of systemic corticosteroids over 10 mg/day prednisone or immunosuppressive therapy before treatment
  • Evidence of leptomeningeal disease
  • Clinically significant corneal disease
  • Severe or uncontrolled systemic diseases or psychiatric illness affecting safety or compliance
  • Active and symptomatic brain or spinal cord metastases requiring corticosteroids or anticonvulsants
  • Inadequate washout periods from prior treatments including radiation, chemotherapy, immunotherapy, or surgery
  • Prior treatment with anti-HER3 antibodies
  • Unresolved toxicities from previous cancer therapies above grade 1 except certain stable chronic conditions
  • Known allergies to HER3-DXd, T-DXd, monoclonal antibodies, or PARP inhibitors
  • Other malignancies within 3 years except certain treated skin or in-situ cancers
  • Significant uncontrolled heart conditions or abnormal heart tests
  • Active hepatitis B or C infection not controlled or resolved
  • Pregnant or breastfeeding women
  • HIV infection not well controlled or unstable
  • Medical or psychiatric conditions that could affect safety or study results
  • Legal incapacity or inability to consent
  • Participation in another experimental drug trial within 4 weeks
  • For module 1, history of hypersensitivity to olaparib or inadequate washout of CYP3A inhibitors or inducers

AI-Screening

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Trial Site Locations

Total: 1 location

1

Gustave Roussy Institut

Villejuif, France, 94805

Actively Recruiting

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Research Team

B

Barbara Pistilli

CONTACT

F

Fernanda Mosele

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

3

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