A Phase II Study of AK146D1 Combined With AK112 in Advanced Breast Cancer

Официальное название

A Phase II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of AK146D1 Combined With AK112 in Patients With Advanced Breast Cancer

Обзор

This is a Phase II clinical study aimed at evaluating the safety, tolerability, antitumor efficacy, PK and immunogenicity of AK146D1 combined with AK112 in advanced breast cancer.

Вмешательства

• Препарат AK146D1 for injection
  AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate.
• Препарат AK112 Injection
  AK112 Injection is a PD-1/VEGF bispecific antibody.

Первичные конечные точки

• Number of participants with dose limiting toxicities (DLTs) [Срок оценки: During the first 3 weeks of treatment in Safety Run-in Phase.]
• Number of participants with adverse events (AEs) [Срок оценки: From the time of signing informed consent form through 30 days(for AEs) or 90 days(for SAEs) after the last dose of study drug.]
• Objective Response Rate (ORR) assessed by investigator per RECIST v1.1 [Срок оценки: Up to approximately 2 years.]

Вторичные конечные точки (7)

• Progression Free Survival (PFS) assessed by investigator per RECIST v1.1 [Срок оценки: Up to approximately 2 years.]
• Disease Control Rate (DCR) assessed per RECIST v1.1 [Срок оценки: Up to approximately 2 years.]
• Duration of response (DoR) assessed by the investigator per RECIST v1.1 [Срок оценки: Up to approximately 2 years.]
• Time to response (TTR) assessed by the investigator per RECIST v1.1 [Срок оценки: Up to approximately 2 years.]
• Overall survival (OS) [Срок оценки: Up to approximately 2 years.]
• Serum PK concentration of AK146D1 and AK112 [Срок оценки: From pre-dose to the end of the last dose, an average of 6 months.]
• Anti-drug antibodies (ADA) [Срок оценки: From pre-dose to 30 days post end of treatment.]

Критерии участия

Критерии включения

• Be able to understand and voluntarily sign the written informed consent form.
• Aged of ≥ 18 years and ≤75 years.
• ECOG PS 0 or 1.
• The expected lifespan is ≥3 months.
• Patients with histologically confirmed locally advanced, recurrent, or metastatic breast cancer who are not eligible for curative surgical resection; and who have histologically or cytologically confirmed HER2-negative disease.
• At least one measurable lesion according to RECIST v1.1. Patients with only bone lesions or cutaneous lesions are not ineligible for enrollment.
• Have sufficient organ function.
• Females patients must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception.

Критерии исключения

• Patients had breast cancer amenable to curative treatment at study enrollment.
• Concurrent other histopathological types confirmed by tumor histology or cytology.
• Having other active malignancies within 3 years.
• Currently participating in another interventional clinical study.
• Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
• Prior treatment with any therapy targeting Trop-2 or Nectin-4, or any chemotherapy agent targeting topoisomerase I.
• Receipt of systemic anti-tumor therapy (including chemotherapy, immunotherapy, biological agents, etc.) within 4 weeks prior to the first dose.
• Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 6.0 grade 1 or lower.
• Patients with clinically significant cardiovascular or cerebrovascular diseases or risks.
• Patients with active autoimmune diseases requiring systemic treatment within 2 years.
• Receipt of systemic anti-infective therapy within 2 weeks prior to the first dose.
• Known to be positive for HIV and other infections.
• Previous history of severe hypersensitivity reactions.
• Live attenuated vaccines were received within 4 weeks.
• Patients with a history of mental illness and incapacitated or limited capacity.
• Any disease or condition that, in the opinion of the investigator, would compromise patient safety or interfere with study assessments.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07591090 · AK146D1-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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