SKB264 Plus KL-A167 in MSI-H/dMMR Advanced Gynecological Malignancies

Официальное название

A Phase II Study of Sacituzumab Tirumotecan (Sac-TMT/SKB264) in Combination With Tagitanlimab (KL-A167) as Second-Line or Later Therapy for MSI-H/dMMR Advanced Gynecological Malignancies: An Open-Label, Single-Arm, Multicenter Exploratory Trial

Обзор

This is a prospective, open-label, multicenter, single-arm Phase II study designed to evaluate the efficacy and safety of sacituzumab tirumotecan (sac-TMT/SKB264) in combination with tagitanlimab (KL-A167) as second-line or later therapy in patients with recurrent or metastatic MSI-H/dMMR gynecological malignancies, including endometrial cancer, ovarian cancer, and cervical cancer. The primary objective is to evaluate the objective response rate (ORR) per RECIST v1.1 as assessed by the investigator. Secondary objectives include evaluating overall survival (OS), progression-free survival (PFS) per RECIST v1.1, disease control rate (DCR), duration of response (DoR), and the safety and tolerability of the combination regimen.

Вмешательства

• Препарат Sacituzumab Tirumotecan (Sac-TMT)
  Sac-TMT will be administered as an intravenous (IV) infusion every 2 weeks on Day 1 of each 14-day cycle.
• Препарат Tagitanlimab
  KL-A167 will be administered as an intravenous (IV) infusion every 2 weeks on Day 1 of each 14-day cycle. KL-A167 therapy for up to 2 years.

Первичные конечные точки

• Objective response rate(ORR) [Срок оценки: up to 24 months]

Вторичные конечные точки (5)

• Progression-free survival(PFS) [Срок оценки: up to 24 months]
• Duration of response (DoR) [Срок оценки: up to 24 months]
• Disease control rate(DCR) [Срок оценки: up to 24 months]
• Overall survival(OS) [Срок оценки: up to 5 years]
• Incidence and severity of adverse events (AEs) [Срок оценки: up to 24 months]

Критерии участия

Критерии включения

• 1\. Age ≥18 years.
• 2\. Histologically or cytologically confirmed recurrent or metastatic ovarian cancer, endometrial cancer, or cervical cancer.
• 3\. dMMR or MSI-H subtype (defined as: deficiency/loss of mismatch repair (MMR) proteins MLH1, PMS2, MSH2, or MSH6 expression detected by immunohistochemistry (IHC), or identified as MSI-H by polymerase chain reaction (PCR)/next-generation sequencing (NGS)).
• 4\. Received at least 1 prior systemic regimen (prior anti-PD-1/L1 allowed) for recurrent or metastatic ovarian cancer, endometrial cancer, or cervical cancer.
• 5\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• 6\. Life expectancy more than 12 weeks.
• 7\. At least one measurable lesion per RECIST 1.1 criteria.
• 8\. Subjects must have recovered from all toxicities related to prior therapies, except for toxicities not considered a safety risk.
• 9\. Adequate function of the important organs.
• 10\. For female subjects of childbearing potential effective medical contraception must be used from the time of signing the informed consent form until 6 months after the last dose of the drug.

11\. Participants must voluntarily participate in the study, sign an informed consent form, exhibit good compliance, and cooperate with follow-up assessments.

Критерии исключения

• 1\. Subjects with known other malignant tumors that are progressing or require active treatment within the past 3 years.
• 2\. Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or other active CNS metastases. Subjects with locally treated brain metastases may participate provided they are clinically stable for at least 4 weeks, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment;
• 3\. Subjects with clinically significant cardiovascular diseases.
• 4\. Subjects with severe and/or uncontrolled concomitant diseases, such as uncontrolled hypertension, symptomatic or recurrent pleural effusion, pericardial effusion, or ascites requiring drainage.
• 5\. Subjects diagnosed with active hepatitis B or active hepatitis C.
• 6\. Subjects with known uncontrolled HIV infection.
• 7\. Subjects with known active tuberculosis.
• 8\. Subjects with documented severe dry eye syndrome, severe meibomian gland dysfunction and/or blepharitis, or a history of corneal disorders that impair or delay corneal healing.
• 9\. Subjects who have undergone major surgery (as defined by the investigator) within 30 days prior to the first dose of study treatment or who have not recovered from prior surgery.
• 10\. Subjects with known hypersensitivity or anaphylaxis to the study drug or its excipients; or a history of severe hypersensitivity reactions to monoclonal antibodies.
• 11\. Subjects with a history of interstitial lung disease (ILD) or non-infectious pneumonia requiring steroid treatment, currently suffering from ILD/pneumonia, or unable to rule out suspected ILD/pneumonia through imaging at screening.
• 12\. Subjects with a history of allogeneic tissue/organ transplantation.
• 13\. Subjects with autoimmune diseases requiring systemic treatment within the past 2 years or requiring immunosuppressive treatment during the study period. Subjects with controllable type 1 diabetes, thyroiditis with normal thyroid function, or hypothyroidism well controlled by hormone replacement therapy (HRT), or skin diseases (such as vitiligo, psoriasis) that do not require systemic treatment can be included.
• 14\. Subjects who have previously received TROP2-targeted drugs or any therapy containing a topoisomerase I inhibitor, including antibody-drug conjugates (ADCs).
• 15\. Subjects who have previously used any experimental anti-tumor vaccines.
• 16\. Subjects who received live vaccines within 30 days prior to the first dose of study treatment or plan to receive live vaccines during the study.
• 17\. Subjects who need to use strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) within 2 weeks before the first study treatment and during the study period.
• 18\. Subjects who received any chemotherapy, radiotherapy, immunotherapy, or biologic therapy within 4 weeks prior to the first dose of study treatment; subjects who received small molecule tyrosine kinase inhibitors (TKIs), anti-tumor hormone therapy, systemic immunostimulants (including but not limited to interferon, IL-2), or approved anti-tumor Chinese herbal preparations within 2 weeks before the first study treatment.
• 19\. Subjects who received systemic anti-infective treatment within 2 weeks prior to the first dose of study treatment.
• 20\. Pregnant or lactating women.
• 21\. Any other conditions deemed by the investigator to make the patient unsuitable for participation in this study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Qilu Hospital of Shandong University — Цзинань
• Peking Union Medical College Hospital — Пекин

Идентификаторы

NCT: NCT07738757 · K10649

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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