JSKN033 Combination Therapy in Subjects With Advanced Cervical Cancer

Официальное название

A Phase II Study to Evaluate the Safety, Efficacy, Pharmacokinetics/Pharmacodynamics of JSKN033 in Combination With Platinum-Based Chemotherapy With or Without Bevacizumab in Patients With Advanced Cervical Cancer

Обзор

The goal of this clinical trial is to learn if the therapy of JSKN033 plus chemotherapy with or with bevacizumab is safe to treat patients with advanced cervical cancer. It will also learn about the antitumor activity and pharmacokinetic/ pharmacodynamic profiles of this therapy.

Подробное описание

This is an open-label, multicenter, Phase II clinical study conducted in China to evaluate the safety and efficacy of JSKN033 in combination with platinum-based chemotherapy with or without bevacizumab in patients with advanced cervical cancer. The study consists of two phases: a safety run-in phase and a dose expansion phase. Enrolled subjects are patients with persistent, recurrent, or metastatic cervical cancer who have not received prior systemic therapy for recurrent or metastatic disease. All subjects will receive treatment with JSKN033 + cisplatin/carboplatin ± bevacizumab. All enrolled subjects will continue treatment until meeting any of the following treatment termination criteria: disease progression, intolerable toxicity, initiation of new anti-tumor therapy, withdrawal of informed consent, loss to follow-up, death, early study termination, or other criteria specified in the protocol for treatment termination, whichever occurs first.

Вмешательства

• Препарат JSKN033
  JSKN033 in combination with platinum-based chemotherapy with or without bevacizumab at selected dose levels according to protocol
• Препарат Platinum
  JSKN033 in combination with platinum-based chemotherapy with or without bevacizumab at selected dose levels according to protocol
• Препарат Bevacizumab
  JSKN033 in combination with platinum-based chemotherapy with or without bevacizumab at selected dose levels according to protocol

Первичные конечные точки

• Frequency and severity of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: 21 days from the first dose]
• Frequency and severity of Treatment-Related Adverse Events (TRAEs) [Срок оценки: 21 days from the first dose]
• Frequency and severity of Serious Adverse Events (SAEs) [Срок оценки: 21 days from the first dose]
• Objective Response Rate (ORR) as assessed by the investigator and IRC per RECIST 1.1. [Срок оценки: From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed at approximately 12 months.]

Вторичные конечные точки (12)

• Disease Control Rate (DCR) [Срок оценки: From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed at approximately 12 months.]
• Time to Response (TTR) [Срок оценки: From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed at approximately 12 months]
• Duration of Response (DoR) [Срок оценки: From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed at approximately 24 months.]
• Progression-Free Survival (PFS) as assessed by the investigator and IRC per RECIST 1.1 [Срок оценки: From the first study drug dose, until: disease progression per RECIST 1.1; initiation of new anti-tumor treatment; withdrawal of informed consent; death; loss to follow-up; or study termination, whichever comes first. Assessed at approximately 24 months.]
• Overall Survival (OS) [Срок оценки: Assessed at approximately 24 months]
• Maximum plasma concentration (Cmax) of JSKN033 [Срок оценки: From the enrollment until the end of study. Assessed up to 24 months.]
• Time to Cmax (Tmax) of JSKN033 [Срок оценки: From the enrollment until the end of study. Assessed up to 24 months.]
• Trough concentration (Ctrough) of JSKN033 [Срок оценки: From the enrollment until the end of study. Assessed up to 24 months.]
• Area under the plasma concentration-time curve of JSKN033 [Срок оценки: From the enrollment until the end of study. Assessed up to 24 months.]
• Volume of distribution (Vz/F) of JSKN033 [Срок оценки: From the enrollment until the end of study. Assessed up to 24 months.]
• Elimination half-life (t1/2) and clearance (CL/F) of JSKN033 [Срок оценки: From the enrollment until the end of study. Assessed up to 24 months.]
• Accumulation index of JSKN033 [Срок оценки: From the enrollment until the end of study. Assessed up to 24 months.]

Критерии участия

Критерии включения

• Voluntarily participate and sign the informed consent form.
• Age ≥ 18 years old, male or female.
• Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
• Expected survival ≥ 3 months.
• Histologically or cytologically confirmed persistent, recurrent, or metastatic (FIGO stage IVB) cervical cancer unsuitable for curative surgery and/or curative radiotherapy, meeting the following criteria:

• Pathological types include squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma;
• No prior systemic therapy for recurrent or metastatic cervical cancer.
• At least one measurable lesion per RECIST 1.1 at baseline.
• Agree to provide recently archived or fresh tumor tissue samples.
• Adequate organ function.
• Female subjects of childbearing potential or male subjects whose partners are of childbearing potential agree to use effective contraceptive measures. Female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose.
• Be able and willing to comply with the visits, treatment plans, laboratory tests, and other study-related procedures specified in the study protocol.

Критерии исключения

• Complicated with other malignant tumors within 3 years before the first dose, except for tumor types that have achieved clinical cure through local treatment with extremely low recurrence risk.
• History of brainstem, meningeal metastasis, spinal cord metastasis or compression, or carcinomatous meningitis; presence of active brain metastasis.
• Screening imaging shows tumor invasion, compression, or occurrence in surrounding important organs or risk of esophagotracheal fistula or esophagopleural fistula, except those judged by the investigator and medical monitor to not affect the patient's enrollment and administration.
• Prior treatment with topoisomerase I inhibitors or antibody-drug conjugates containing topoisomerase I inhibitors.
• Inadequate washout period of previous therapy.
• Presence of the risk factors related to interstitial lung disease (ILD) or non-infectious pneumonia:
• Presence of clinically severe respiratory impairment caused by pulmonary disease complications.
• Presence of cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors.
• Gastrointestinal abnormalities with obvious clinical manifestations.
• Significant serous effusion.
• Active autoimmune diseases requiring systemic treatment.
• Uncontrolled infection.
• Toxicity of previous anti-tumor treatment has not fully or partially recovered.
• History of allogeneic bone marrow or organ transplantation.
• Known allergy to any component of the study drug/platinum, or history of severe allergic reactions to other antibody drugs.
• Pregnant and/or lactating women, or planning to become pregnant during the study period.
• Known history of mental illness, substance abuse, alcoholism, etc., or other situations that the investigator deems may affect the safety or compliance of the study drug treatment.
• Any other previous or current diseases, treatments, or laboratory test abnormalities that the investigator deems may confuse the study results, affect the patient's full participation in the study, or participation in the study may not be in the best interest of the patient.
• Local or systemic diseases caused by non-malignant tumors, or diseases or symptoms secondary to tumors, which may lead to high medical risks and/or uncertainty in survival assessment, such as tumor-related leukemia reaction (white blood cell count > 20×10⁹/L), cachexia manifestations, etc.
• Known contraindications to bevacizumab or allergy to its components, or the medical conditions affecting its safe use (Note: Applicable only to subjects planned to receive bevacizumab).

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 · 2 центра

• Sun Yat-sen University Cancer Center — Гуанчжоу
• Zhejiang Cancer Hospital — Ханчжоу

Идентификаторы

NCT: NCT07497074 · JSKN033-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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