RecruitingPhase IIEN original

Tucatinib and Trastuzumab in HER3-mutant and HER2-not Amplified Metastatic Breast Cancer

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This is not medical advice. AI-assisted translation — inaccuracies may occur. Always verify the original and consult your oncologist before taking any steps.

About the trial

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.

Original English text from ClinicalTrials.gov

Who can (and can't) join

✓ Qualifies

  • Wiek 18 lat lub więcej
  • Rak piersi z przerzutami lub niemożliwy do operacyjnego usunięcia
  • Brak receptora HER2 (potwierdzone badaniem laboratoryjnym)
  • Co najmniej 2 wcześniejsze chemioterapie na zaawansowanego raka piersi
  • Mutacja genu ERBB3 typu IV lub V potwierdzona w próbce nowotworu
  • Dobry stan ogólny (ECOG ≤ 2)
  • Prawidłowa funkcja serca, nerek i wątroby (wyniki badań laboratoryjnych w normie)
  • Zdolność do przyjmowania leków doustnych i wyrażenie pisemnej zgody na udział

✗ Disqualifies

  • Wcześniejsze leczenie ukierunkowane na receptor HER2 (z wyjątkiem trastuzumab deruxetcan)
  • Uczulenie na trastuzumab, tucatinib lub podobne leki
  • Ciąża, karmienie piersią lub planowanie ciąży
  • Niemożność połykania tabletek lub choroby żołądkowo-jelitowe uniemożliwiające wchłanianie leków
  • Stosowanie leków hamujących metabolizm leków doświadczalnych w ostatnich dniach przed badaniem
  • Jakiekolwiek wcześniejsze leczenie przeciwnowotworowe w ostatnich 4 tygodniach

Simplified criteria — AI translation

Trial details

Minimum age
18 Years
Last updated (source)
February 23, 2026
Sex
No restrictions

Therapies / drugs in trial

Locations (9)

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, France

Chu Dupuytren- Limoges

Limoges, France

Institut Paoli-Calmettes

Marseille, France

Centre Antoine Lacassagne

Nice, France

CHU de Nîmes

Nîmes, France

Centre Eugène Marquis

Rennes, France

Institut Curie_ Site Saint-Cloud

Saint-Cloud, France

Institut Universitaire du Cancer de Toulouse (IUCT) - Oncopole Claudius Regaud

Toulouse, France

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Trial contact

Sandra Clinical Project Manager

Sandra Regulatory Assistant

Contact information from ClinicalTrials.gov. Contact in English.

Data from ClinicalTrials.gov. AI-assisted translation, last sync: 7/1/2026.