A Phase II Study of AK146D1 in Combination With AK112 in Advanced Non-Small Cell Lung Cancer

Официальное название

A Phase II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antitumor Efficacy of AK146D1 in Combination With AK112 or Other Anticancer Therapies in Patients With Advanced Non-Small Cell Lung Cancer

Обзор

This is a phase II clinical study evaluating the safety, tolerability, pharmacokinetics and antitumor efficacy of AK146D1 in combination with AK112 or other anticancer therapies in patients with advanced Non-Small Cell Lung Cancer.

Вмешательства

• Препарат AK146D1 for injection
  AK146D1 for injection is an anti-Trop2/Nectin4 bispecific antibody-drug conjugate.
• Препарат AK112 Injection
  AK112 is a PD-1/VEGF bispecific antibody.
• Препарат Platinum chemotherapy
  Carboplatin or cisplatin will be administered.
• Препарат Osimertinib
  Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI).

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 or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-small cell lung cancer (NSCLC) who are not eligible for curative surgical resection and cannot receive definitive concurrent or sequential chemoradiotherapy.
• At least one measurable non-brain lesion according to RECIST v1.1.
• Have sufficient organ function.
• Females subjects must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception.

Критерии исключения

• NSCLC mixed with a component of small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma.
• 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.
• Having received any treatment targeting Trop2 or Nectin4.
• Prior chemotherapy or antibody-drug conjugate (ADC) therapy targeting topoisomerase I inhibitors.
• Receipt of systemic anti-tumor therapy (including chemotherapy, immunotherapy, biological agents, etc.) within 4 weeks (or 5 half-lives of the drug, whichever is longer) prior to the first dose.
• Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 6.0 grade 1 or lower.
• Subjects with clinically significant cardiovascular or cerebrovascular diseases or risks.
• Subjects 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.
• Subjects with a history of mental illness and incapacitated or limited capacity.
• Any disease or condition that, in the opinion of the investigator, would compromise subject 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

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• SunYat-sen University Cancer Center — Гуанчжоу

Идентификаторы

NCT: NCT07669779 · AK146D1-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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