A Phase II Study of Trastuzumab Deruxtecan (T-DXd) Plus Pyrotinib in HER2-Positive Advanced Breast Cancer After Progression on T-DXd

Conditions

• Breast Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Trastuzumab Deruxtecan (T-DXd) — DRUG
  Intravenous infusion at 5.4 mg/kg on Day 1 of each 21-day cycle. The first infusion is administered over not less than 90 minutes; if well tolerated, subsequent infusions may be shortened to approximately 30 minutes. Protocol-defined dose reduction levels are 4.4 mg/kg (first reduction) and 3.2 mg/kg (second reduction); further reduction requires treatment discontinuation.
• Pyrotinib — DRUG
  Oral tablet, 320 mg once daily on a continuous schedule, taken with or immediately after a meal. A single dose reduction to 240 mg once daily is permitted for toxicity management; multiple interruptions and dose adjustments are allowed.

Study Details

This is a single-arm, exploratory, phase II study evaluating the efficacy and safety of trastuzumab deruxtecan (T-DXd) in combination with pyrotinib in patients with HER2-positive advanced breast cancer whose disease has progressed after prior treatment with T-DXd.T-DXd is the established standard second-line therapy for HER2-positive advanced breast cancer. However, acquired resistance inevitably develops, and there is currently no approved standard treatment for patients progressing after T-DXd. Real-world studies report an objective response rate (ORR) of approximately 14.5% and a median progression-free survival of only 3 to 4 months in this setting, representing a major unmet medical need.Pyrotinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor that potently inhibits HER1, HER2 and HER4 kinase activity and blocks downstream PI3K/AKT and MAPK signaling. Preclinical and clinical data (including the HER2CLIMB-02 and TROPHY studies) support the synergistic potential of combining an anti-HER2 antibody-drug conjugate with a tyrosine kinase inhibitor.Participants receive T-DXd 5.4 mg/kg intravenously on Day 1 of each 21-day cycle plus pyrotinib 320 mg orally once daily, continuously, until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria. Tumor response is assessed using RECIST v1.1.The primary endpoint is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety/tolerability. Approximately 28 participants will be enrolled.

Key Dates

First listed

Sep 23, 2026

Start date

Oct 10, 2026

Status verified

Sep 2026

Primary completion

Oct 30, 2028

Completion

Oct 30, 2029

Study Design

Enrollment

28 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: T-DXd plus Pyrotinib
  Trastuzumab Deruxtecan (T-DXd): Intravenous infusion at 5.4 mg/kg on Day 1 of each 21-day cycle. The first infusion is administered over not less than 90 minutes; if well tolerated, subsequent infusions may be shortened to approximately 30 minutes. Protocol-defined dose reduction levels are 4.4 mg/kg (first reduction) and 3.2 mg/kg (second reduction); further reduction requires treatment discontinuation. Pyrotinib:Oral tablet, 320 mg once daily on a continuous schedule, taken with or immediately after a meal. A single dose reduction to 240 mg once daily is permitted for toxicity management; multiple interruptions and dose adjustments are allowed.

Primary Outcome Measure

The objective response rate（ORR） was evaluated according to the RECIST v1.1 standard [ Time Frame: 3 years ]

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