Actively Recruiting
Phase 1b/2 Multicenter Open-label Dose-Expansion Study of HER3-DXd Alone and with Olaparib in Inoperable Advanced Breast Cancer After Progression on T-DXd
Led by Gustave Roussy, Cancer Campus, Grand Paris · Updated on 2024-03-29
152
Participants Needed
1
Research Sites
91 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
Researchers are evaluating HER3-DXd monotherapy and its combination with other cancer treatments in patients with advanced breast cancer (ABC) who have progressed after treatment with T-DXd. This open-label, multicenter phase 1b/2 study focuses on safety, tolerability, and effectiveness of these therapies. The first two modules assess HER3-DXd with olaparib in HER2-low and HER2-positive ABC and HER3-DXd alone in HER2-low ABC after progression on T-DXd. Participants receive intravenous HER3-DXd monotherapy at 5.6 mg/kg every 21 days in initial safety and dose-finding parts. In the dose expansion phase, patients receive the recommended phase 2 dose of HER3-DXd alone or combined with olaparib. Treatment continues in modules designed to explore monotherapy and combination therapy effects, with dosing schedules maintained every 21 days. Participants undergo safety and response evaluations including monitoring for dose-limiting toxicities, laboratory abnormalities, and radiographic signs of lung conditions over 21 months for early parts and up to 51 months for efficacy assessments. Researchers measure objective response rates, duration of response, progression-free survival, and clinical benefit rate. Patients provide biopsies and undergo routine laboratory and imaging assessments while treatment modifications due to side effects are tracked. The study spans several years with ongoing safety and pharmacokinetic evaluations.
CONDITIONS
Brief 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
Eligibility Criteria
You may qualify if you...
- Patients aged 18 years or older
- Histologically confirmed advanced breast cancer that is HER2-positive or HER2-low
- Prior treatment with T-DXd and disease progression during or within 2 months after stopping it
- HER2-positive patients must have received trastuzumab and taxanes; HER2-low patients must have received 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
- ECOG performance status of 0 or 1 at screening
- At least one measurable lesion by RECIST 1.1 criteria
- Tumor site accessible for biopsy and willingness to provide biopsies
- Adequate bone marrow and organ function within 14 days before treatment
- Negative pregnancy test and agreement to use effective contraception for females of childbearing potential
- Male patients must be surgically sterile or agree to use effective birth control
- Ability to understand and sign informed consent and comply with study procedures
- Affiliated to a social security system or beneficiary
You will not qualify if you...
- Breast cancer suitable for surgery or radiation with curative intent
- History or current evidence of interstitial lung disease or pulmonary fibrosis
- Severe pulmonary conditions or autoimmune diseases affecting lungs
- Use of chronic systemic corticosteroids over 10 mg/day prednisone or equivalent before treatment
- Evidence of leptomeningeal disease
- Clinically significant corneal disease
- Severe or uncontrolled systemic diseases or psychiatric illness that may affect safety or compliance
- Active or symptomatic brain metastases requiring corticosteroids or anticonvulsants
- Recent anticancer therapies or radiotherapy not meeting washout periods
- Prior treatment with anti-HER3 antibodies
- Unresolved toxicities from previous cancer treatments above grade 1, except stable grade 2 neuropathy or fatigue
- Known hypersensitivity to HER3-DXd, T-DXd, or PARP inhibitors
- Other malignancies within 3 years except certain treated skin or in-situ cancers
- Significant cardiovascular disorders including prolonged QT, low ejection fraction, recent myocardial infarction, or arrhythmias
- Active hepatitis B or C infection not meeting viral load criteria
- Pregnant or breastfeeding females
- Uncontrolled HIV infection
- Any medical or psychiatric condition that could affect safety or study results
- Legal incapacity or under legal protection
- Participation in another experimental drug trial within 4 weeks
- For module 1, history of hypersensitivity to olaparib or inadequate washout from certain drugs
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to several treatment cycles during dose finding
Participants receive HER3-DXd monotherapy at 5.6 mg/kg by intravenous infusion every 21 days to assess safety and tolerability.
Repeated visits every 3 weeks for treatment administration
Duration - Repeated 21-day cycles until disease progression or discontinuation
Participants receive assigned treatment with HER3-DXd alone or combined with olaparib, dosed in 21-day cycles as defined in the dose expansion parts.
Repeated visits every 3 weeks for treatment administration
Duration - Up to several months after treatment ends
Participants are monitored for safety, tolerability, and anti-tumor activity after treatment ends.
Scheduled visits as needed for safety assessments
Trial Site Locations
Total: 1 location
1
Gustave Roussy Institut
Villejuif, France, 94805
Actively Recruiting
Research Team
B
Barbara Pistilli
F
Fernanda Mosele
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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