OncoMatch/Clinical Trials/NCT07193394
Tucatinib and Trastuzumab in HER3-mutant and HER2-not Amplified Metastatic Breast Cancer
Is NCT07193394 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Tucatinib (ONT-380) and Trastuzumab (Herceptin) for metastatic breast cancer ( her2 negative).
Treatment: Tucatinib (ONT-380) · Trastuzumab (Herceptin) — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Breast Carcinoma
Biomarker criteria
Required: HER2 (ERBB2) negative (IHC 0+, IHC 1+, or IHC 2+ and ISH non-amplified, per ASCO/CAP guidelines) (IHC 0+, IHC 1+, or IHC 2+ and ISH non-amplified)
HER2-negative (defined as having an IHC 0+, IHC 1+, or IHC 2+ and ISH non-amplified, per ASCO/CAP guidelines) on last assessable tumor sample
Required: ERBB3 Class IV or V somatic mutation
Class IV or V somatic ERBB3 mutation as determined on a tumor sample obtained during the molecular screening step
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Must have received: antibody-drug conjugate — advanced breast cancer
including at least one line of conjugated antibody
Cannot have received: HER2-targeted therapy
Exception: Prior treatment with trastuzumab deruxtecan is allowed, per label, in patients with HER2-low metastatic breast cancer (IHC 1+ or 2+, ISH non-amplified)
Having received any prior treatment targeting HER2. Prior treatment with trastuzumab deruxtecan is allowed, per label, in patients with HER2-low metastatic breast cancer (IHC 1+ or 2+, ISH non-amplified)
Lab requirements
Kidney function
Creatinine clearance ≥ 50 mL/min as calculated per institutional guidelines
Liver function
Total bilirubin ≤1.5 X ULN (except Gilbert's disease: conjugated bilirubin ≤1.5 X ULN); AST/ALT ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases)
Cardiac function
Left ventricular ejection fraction (LVEF) ≥50% as assessed by ECHO or MUGA within 4 weeks prior to first dose
Adequate organ function: Creatinine clearance ≥ 50 mL/min; Total bilirubin ≤1.5 X ULN (except Gilbert's disease: conjugated bilirubin ≤1.5 X ULN); AST/ALT ≤ 2.5 X ULN (≤ 5 X ULN if the patient has liver metastases); LVEF ≥50% as assessed by ECHO or MUGA
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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