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Neoadjuvant Dalpiciclib + AI → SHR-A1811 for HR+/HER2-Low Breast Cancer (TD-DASHER-01)

8 de junho de 2026 atualizado por: Tang-Du Hospital

Dalpiciclib Combined With Aromatase Inhibitor (AI) Followed by SHR-A1811 as Neoadjuvant Therapy in Patients With Intermediate-to-High Risk HR+/HER2-Low Breast Cancer: A Phase II Exploratory Study

This is a phase II, single-arm, prospective exploratory study to evaluate the efficacy and safety of neoadjuvant dalpiciclib (a CDK4/6 inhibitor) plus an aromatase inhibitor (AI) followed by SHR-A1811 (an anti-HER2 antibody-drug conjugate) in patients with intermediate-to-high risk, hormone receptor-positive (HR+), HER2-low breast cancer. Patients will receive dalpiciclib (125 mg orally once daily, days 1-21, every 4 weeks) plus AI (anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg once daily) for 4 cycles, followed by SHR-A1811 (4.8 mg/kg intravenously every 3 weeks) for 4 cycles. The primary endpoint is objective response rate (ORR) per RECIST 1.1. Secondary endpoints include pathological complete response (pCR), breast-conserving surgery rate, event-free survival (EFS), change in Ki-67 index, and safety. A total of 20 participants will be enrolled.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

This is a single-arm, open-label, phase II exploratory trial conducted at a single center (Second Affiliated Hospital of Air Force Medical University, China). The study aims to investigate the activity and safety of dalpiciclib plus an aromatase inhibitor (AI) followed by the HER2-directed antibody-drug conjugate (ADC) SHR-A1811 as neoadjuvant therapy for patients with intermediate-to-high risk, hormone receptor-positive (HR+), HER2-low breast cancer.

Preclinical evidence suggests that CDK4/6 inhibition may enhance the immunogenic cell death induced by ADCs and overcome tumor heterogeneity. Dalpiciclib is a selective CDK4/6 inhibitor with a distinct piperidine structure associated with low hepatotoxicity and minimal gastrointestinal side effects. SHR-A1811 is a HER2-targeted ADC composed of a humanized anti-HER2 IgG1 monoclonal antibody (based on trastuzumab sequence), a cleavable maleimide tetrapeptide (GGFG) linker, and a DNA topoisomerase I inhibitor (SHR169265). It demonstrates bystander killing of HER2-low cells. The 4-cycle induction with dalpiciclib plus AI prior to SHR-A1811 is designed to reduce tumor proliferation and potentially prime the tumor microenvironment before ADC administration.

Treatment administration

  • Dalpiciclib: 125 mg orally once daily on days 1-21 of each 28-day cycle (4 cycles total). Patients are instructed to take the tablet at approximately the same time each day, on an empty stomach (≥1 hour before or after food). Missed doses are not supplemented; vomiting within a short time after intake does not trigger a replacement dose. Interruption for >21 consecutive days requires study discontinuation. Dose reductions follow a stepwise scheme: 125 mg → 100 mg → 75 mg.
  • Aromatase inhibitor (AI): Investigator's choice of anastrozole 1 mg daily, letrozole 2.5 mg daily, or exemestane 25 mg daily, taken continuously during the first 4 cycles. Premenopausal patients (mandatory) and perimenopausal patients (at investigator's discretion) receive concomitant LHRH agonists (e.g., goserelin or leuprolide).
  • SHR-A1811: 4.8 mg/kg intravenously over a standard infusion duration on day 1 of each 21-day cycle (4 cycles total). The dose is recalculated based on body weight measured immediately before each cycle. If weight change from baseline is <10%, no dose adjustment is required. Dose reductions follow a 4.8 → 3.2 mg/kg step. Infusion-related reactions are managed according to a predefined algorithm (slow infusion, antihistamines, corticosteroids, or permanent discontinuation for grade ≥3 reactions).

Tipo de estudo

Intervencional

Inscrição (Estimado)

20

Estágio

  • Fase 2

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

Inclusion Criteria:

  1. Age ≥18 and ≤70 years
  2. Histologically confirmed invasive breast cancer, HR+ (ER ≥1% and/or PR ≥1%) and HER2-low (IHC 1+ or IHC 2+/ISH-)
  3. No prior systemic anti-tumor therapy for breast cancer
  4. Stage II-III (T1cN1-2M0, T2-4N0-2M0) per AJCC 8th edition

  5. At least one of the following intermediate-to-high risk factors:

    • Axillary lymph node involvement ≥1
    • Tumor size≥2 cm
    • Grade 3 tumor
    • Ki-67 ≥20%
  6. At least one measurable lesion per RECIST 1.1
  7. ECOG PS 0-1
  8. Adequate organ function (ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, Hb ≥90 g/L, TBIL ≤1.5×ULN, ALT/AST ≤2.5×ULN, Cr ≤1.5×ULN or CrCl ≥60 mL/min, LVEF ≥50%, QTcF ≤470 ms in females, DLCO ≥50% predicted
  9. Negative pregnancy test (for women of childbearing potential) and agreement to use adequate contraception during and for 6 months after treatment
  10. Willing and able to provide informed consent and comply with study procedures

Exclusion Criteria:

  1. Non-pathologically confirmed breast cancer
  2. Bilateral, inflammatory, or occult breast cancer
  3. Prior anticancer therapy (chemotherapy, radiotherapy, targeted therapy, endocrine therapy, etc.)
  4. Concurrent use of other anticancer treatments
  5. Other malignancy within 5 years (except cured basal cell carcinoma or cervical carcinoma in situ)
  6. Participation in another interventional clinical trial within 4 weeks prior to first dose
  7. Use of immunosuppressive agents or systemic corticosteroids (>10 mg/day prednisone or equivalent) within 2 weeks prior to first dose
  8. Live or attenuated vaccine within 4 weeks prior to first dose
  9. Major surgery unrelated to breast cancer within 4 weeks prior to first dose
  10. Active or history of autoimmune disease requiring systemic treatment
  11. Known immunodeficiency (e.g., HIV positivity) or history of organ transplantation
  12. Uncontrolled or significant cardiovascular disease (e.g., NYHA class III/IV heart failure, myocardial infarction, unstable angina, arrhythmia requiring treatment, QTcF >470 ms, uncontrolled hypertension)
  13. Known or suspected interstitial lung disease (ILD) or significant pre-existing pulmonary disease
  14. Active hepatitis B (HBsAg positive and HBV DNA ≥500 IU/mL) or hepatitis C (HCV RNA above ULN), cirrhosis, or uncontrolled severe infection
  15. Known bleeding or thrombotic tendency
  16. Allergy or contraindication to any study drug or excipient
  17. Pregnancy, breastfeeding, or positive pregnancy test at baseline
  18. Any concurrent condition that may compromise patient safety or study compliance (e.g., uncontrolled hypertension, severe diabetes, active infection)
  19. History of neurological or psychiatric disorders (e.g., epilepsy, dementia) or any condition deemed unsuitable by the investigator.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Dalpiciclib + Aromatase Inhibitor followed by SHR-A1811
Medicamento: Dalpiciclib 125mg
CDK4/6 inhibitor, 125 mg oral tablet, taken once daily on days 1-21 of each 28 day cycle for 4 cycles.
Medicamento: Aromatase Inhibitor
Includes anastrozole 1 mg/day, letrozole 2.5 mg/day, or exemestane 25 mg/day, administered orally once daily for 4 cycles.
Medicamento: SHR-A1811
Anti-HER2 antibody-drug conjugate (ADC), 4.8 mg/kg intravenous infusion once every 3 weeks for 4 cycles

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Objective Response Rate (ORR)
Prazo: After completion of 8 cycles of neoadjuvant therapy (Cycles 1-4: 28 days/cycle; Cycles 5-8: 21 days/cycle), within 4 weeks prior to surgery
Proportion of patients achieving complete response (CR) or partial response (PR) per RECIST 1.1
After completion of 8 cycles of neoadjuvant therapy (Cycles 1-4: 28 days/cycle; Cycles 5-8: 21 days/cycle), within 4 weeks prior to surgery

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Breast-Conserving Surgery Rate
Prazo: At the time of surgery
Proportion of participants who undergo breast-conserving surgery (BCS) after neoadjuvant therapy. BCS is defined as surgical resection of the primary tumor with negative margins while preserving the breast contour, as opposed to total mastectomy.
At the time of surgery
Event-Free Survival (EFS)
Prazo: From enrollment up to 5 years after last patient enrollment (assessed every 3 months during the first year, then every 6 months thereafter
EFS is defined as the time from enrollment to the first occurrence of any of the following events: disease progression (local, regional, or distant) during neoadjuvant therapy, disease recurrence after surgery (local, regional, or distant), contralateral breast cancer, any secondary malignancy, or death from any cause. Participants without an event at the time of last follow-up are censored.
From enrollment up to 5 years after last patient enrollment (assessed every 3 months during the first year, then every 6 months thereafter
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Prazo: From signing of informed consent through 30 days after the last dose of study drug, or until initiation of new anticancer therapy, whichever occurs first.
Safety outcomes include: incidence of any AE, incidence of grade ≥3 AE (per NCI-CTCAE version 6.0), incidence of SAEs, incidence of AE leading to treatment discontinuation or dose modification, and incidence of AE by system organ class and preferred term. Laboratory abnormalities, vital signs, ECG parameters (QTcF, heart rate), and left ventricular ejection fraction (LVEF) are also summarized.
From signing of informed consent through 30 days after the last dose of study drug, or until initiation of new anticancer therapy, whichever occurs first.
Pathological Complete Response Rate (pCR): ypT0-is/ypN0
Prazo: At the time of surgery, performed within 4 weeks after completion of 8 cycles of neoadjuvant therapy (Cycles 1-4: 28 days/cycle; Cycles 5-8: 21 days/cycle).
pCR is defined as absence of invasive carcinoma in the breast primary tumor (ypT0/is) and absence of tumor cells in axillary lymph nodes (ypN0) on pathological examination of the surgical specimen after neoadjuvant therapy. Presence of ductal carcinoma in situ (DCIS) alone is allowed.
At the time of surgery, performed within 4 weeks after completion of 8 cycles of neoadjuvant therapy (Cycles 1-4: 28 days/cycle; Cycles 5-8: 21 days/cycle).
Ki-67 Index Change
Prazo: Baseline (pre-treatment core needle biopsy) and at surgery (post-neoadjuvant surgical specimen).
Ki-67 index is measured by immunohistochemistry (IHC) as the percentage of tumor cells with positive nuclear staining. The scale is the Ki-67 proliferation index, which ranges from 0% (minimum) to 100% (maximum). Higher scores indicate a worse outcome (higher proliferative activity). The change is calculated as Ki-67 index at surgery minus Ki-67 index at baseline. A negative value (reduction) indicates a better outcome (decreased proliferation), while a positive value (increase) indicates a worse outcome.
Baseline (pre-treatment core needle biopsy) and at surgery (post-neoadjuvant surgical specimen).

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Tang-Du Hospital

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de junho de 2026

Conclusão Primária (Estimado)

1 de junho de 2028

Conclusão do estudo (Estimado)

1 de janeiro de 2029

Datas de inscrição no estudo

Enviado pela primeira vez

24 de maio de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

24 de maio de 2026

Primeira postagem (Real)

1 de junho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

11 de junho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

8 de junho de 2026

Última verificação

1 de junho de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • TD-DASHER-01

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Descrição do plano IPD

The informed consent form signed by participants does not include provisions for sharing individual participant data with external researchers.

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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