Actively Recruiting
Tucatinib and Trastuzumab in HER3-mutant and HER2-not Amplified Metastatic Breast Cancer
Led by Institut Curie · Updated on 2026-02-23
20
Participants Needed
9
Research Sites
174 weeks
Total Duration
On this page
Sponsors
I
Institut Curie
Lead Sponsor
P
Pfizer
Collaborating Sponsor
AI-Summary
What this Trial Is About
The H3RAKLES trial would allow patients with a progressive metastatic breast cancer to have access to one more line of systemic therapy. Patients included in this trial will have already received at least two lines of chemotherapy (and potentially several lines of endocrine therapy for patients with a HR+ disease). In this setting, few treatments have demonstrated a clinically meaningful benefit, and any additional option is valuable. Furthermore, the pre-clinical and clinical rationale indicate a high probability of clinical benefit, as previously shown in Table 1, with all patients treated with trastuzumab and a TKI targeting HER2 displaying a response. Besides, with several years of hindsight for the combination of lapatinib, trastuzumab and capecitabine, we expect excellent tolerance with the same treatment without capecitabine. The H3RAKLES single-arm phase II trial will evaluate the combination of tucatinib, a HER2 TKI, and trastuzumab, a HER2-directed antibody in patients with a HER2-not amplified metastatic or unresectable breast cancer harboring an activating ERBB3 mutation. To demonstrate the actionability of ERBB3 mutations, all patients will receive a combination of trastuzumab and tucatinib, in 3-weeks cycles.
CONDITIONS
Official Title
Tucatinib and Trastuzumab in HER3-mutant and HER2-not Amplified Metastatic Breast Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Diagnosed with metastatic or unresectable breast cancer
- HER2-negative status confirmed by IHC 0+, 1+, or 2+ and ISH non-amplified per guidelines
- Received at least two prior chemotherapy lines for advanced breast cancer, including at least one conjugated antibody line or PARP inhibitor if BRCA mutation present
- Presence of class IV or V somatic ERBB3 mutation detected on tumor sample
- ECOG performance status of 2 or less
- Measurable disease according to RECIST v1.1 criteria
- Left ventricular ejection fraction of 50% or higher within 4 weeks prior to treatment start
- Adequate organ function including creatinine clearance ≥ 50 mL/min, bilirubin ≤ 1.5 times upper limit of normal (ULN) unless Gilbert's disease, and transaminases ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases present)
- Women of childbearing potential must have negative pregnancy test within 7 days before first dose
- Women of childbearing potential and men with partners of childbearing potential must agree to use effective contraception during and for 3 months after treatment
- Eligible for treatment according to investigator's opinion
- Covered by health insurance
- Able to provide signed informed consent
You will not qualify if you...
- Previous treatment targeting HER2, except trastuzumab deruxtecan allowed for HER2-low metastatic breast cancer
- History of allergic reactions to trastuzumab, tucatinib, or similar drugs
- Pregnant, breastfeeding, or planning pregnancy from consent until 7 months after last dose
- Unable to swallow pills or have significant gastrointestinal disease or surgery affecting medication absorption
- Use of strong CYP2C8 inhibitors within 5 half-lives or strong CYP3A4/CYP2C8 inducers within 5 days prior to treatment
- Received systemic anti-cancer therapy, non-CNS radiation, or experimental agent within 3 weeks before treatment, except GnRH agonists
- Participation in another interventional clinical trial
- Symptomatic or untreated brain metastases, brain metastases needing urgent treatment, or requiring high-dose dexamethasone (>2 mg)
- Whole brain radiotherapy within 21 days or stereotactic radiotherapy within 7 days before treatment
- Leptomeningeal metastases
- Major surgery within 21 days before treatment
- Another malignancy treated systemically within 2 years before study start
- Myocardial infarction or unstable angina within 24 weeks before treatment
- Significant cardiopulmonary disease including ventricular arrhythmia, uncontrolled hypertension, symptomatic congestive heart failure, severe dyspnea at rest, hypoxia except for obstructive sleep apnea, or grade 2 or higher QTc prolongation
- Conditions causing drug-induced QT prolongation or torsade de pointes risk
- Active hepatitis B or C infection, or other chronic liver disease
- HIV positive
- Altered mental status or psychiatric disorder preventing valid consent
- Difficulty undergoing trial procedures due to geographic, social, or psychological reasons
- Persons under guardianship or deprived of liberty
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 9 locations
1
Polyclinique Bordeaux Nord Aquitaine
Bordeaux, France, 33 300
Not Yet Recruiting
2
Chu Dupuytren- Limoges
Limoges, France, 87 042
Not Yet Recruiting
3
Institut Paoli-Calmettes
Marseille, France, 13009
Not Yet Recruiting
4
Centre Antoine Lacassagne
Nice, France, 06 189
Not Yet Recruiting
5
CHU de Nîmes
Nîmes, France, 30 029
Not Yet Recruiting
6
Centre Eugène Marquis
Rennes, France, 35 042
Not Yet Recruiting
7
Institut Curie_ Site Saint-Cloud
Saint-Cloud, France, 92 210
Actively Recruiting
8
Institut Universitaire du Cancer de Toulouse (IUCT) - Oncopole Claudius Regaud
Toulouse, France, 31 059
Not Yet Recruiting
9
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, France, 54 519
Not Yet Recruiting
Research Team
S
Sandra Clinical Project Manager
CONTACT
S
Sandra Regulatory Assistant
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here