A Phase 1 Clinical Study to Evaluate the Safety and Efficacy of WSK-IM02 in Patients With Platinum-resistant Recurrent Ovarian Cancer.

Официальное название

A Phase 1, Single-arm, Single-center, Open-label, Prospective Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy of WSK-IM02 in Patients With Platinum-resistant Recurrent Ovarian Cancer.

Обзор

A Phase 1, single-arm, single-center, open-label, prospective, dose-escalation, and cohort expansion study to assess the safety, tolerability, pharmacokinetic (PK), and preliminary efficacy of WSK-IM02 administered as a single agent to patients with platinum-resistant recurrent ovarian cancer.

Подробное описание

Dose-escalation part of this study will assess the safety, tolerability, PK, and preliminary efficacy of WSK-IM02 as monotherapy in eligible patients with platinum-resistant recurrent ovarian cancer. Cohort expansion part will further evaluate the Recommended Phase 2 Dose (RP2D) of WSK-IM02. RP2D decisions will be based on the totality of data, including Dose-Limiting Toxicities (DLTs), tolerability, PK, pharmacodynamics (PD), and efficacy, as available. Dose-escalation part of this study will use a standard 3+3 dose-escalation design with the dose escalated in successive cohorts of 3 to 9 patients each within each cohort in an open-label fashion. Patients who meet eligibility criteria will be enrolled in the dose-escalation part, receiving WSK-IM02 as monotherapy via intraperitoneal injection twice weekly on Days 1, 5, 8, and 12 of repeated 14-day cycles in escalating doses. Patients will only receive WSK-IM02 for one cycle during the 28-day DLTs observation period. If a patient shows no disease progression or intolerable toxicity after completing DLTs observation, the investigator will discuss with the patient whether to continue subsequent treatment. If treatment is continued, the patient enters the treatment period. Enrollment for the next Dose Level can only begin once all patients at a given Dose Level have completed DLTs observation and have not met the termination criteria for dose escalation, and the safety has been evaluated and declared to be safe by the Safety Review Committee (SRC). After determination of Maximum Tolerated Dose (MTD) or Maximum Administrated Dose (MAD) and the expected effective Dose Level, the next part with expansion cohorts will commence to further evaluate the RP2D.

Вмешательства

• Препарат WSK-IM02
  3.33 μg/kg, 8.33 μg/kg, or 16.67 μg/kg of WSK-IM02 as monotherapy via intraperitoneal injection.
• Препарат WSK-IM02
  Expected effective dose level of of WSK-IM02 as monotherapy via intraperitoneal injection.

Первичные конечные точки

• Dose-escalation part: Observation of DLT [Срок оценки: 4 weeks]
• Dose-escalation part: Determination of the MTD or MAD [Срок оценки: 4 weeks]

Критерии участия

Критерии включения

• Female, age ≥18 years old, ≤ 75 years old.
• Willing to voluntarily sign the informed consent form.
• Patients must have histopathologically confirmed ovarian cancer, with no requirement for additional tumor tissue biopsy during the screening period.
• Platinum-resistant recurrent ovarian cancer, with an initial response to ≥4 cycles of platinum-based therapy, followed by confirmed disease recurrence or progression 28 days to 6 months after the last platinum-containing regimen. At least one subsequent systemic therapy for recurrence/progression following platinum resistance, with ≤3 prior lines of systemic therapy (neoadjuvant + adjuvant chemotherapy/adjuvant chemotherapy counts as one chemotherapy line. Other maintenance therapies may be excluded upon investigator and sponsor 's agreement.
• ECOG performance status: 0 - 2.
• Life expectancy ≥3 months.
• Adequate major organ function within 14 days prior to treatment : Hematology (without transfusion or hematopoietic growth factor support within 14 days): NEUT ≥1.5×10⁹/L, PLT ≥100×10⁹/L, Hb ≥80 g/L. Liver function: ALT ≤2.5 × ULN, AST ≤2.5 × ULN. In the presence of liver metastases, ALT and AST ≤5 × ULN. Renal function: Cr ≤1.5 × ULN or Ccr >50 mL/min. Coagulation function: APTT ≤1.5 × ULN, INR ≤1.5 × ULN.
• At least one measurable lesion per RECIST v1.1 criteria.
• Female subjects of childbearing potential must agree to use effective contraceptive methods from signing ICF until at least 6 months after the last dose of the investigational product.

Критерии исключения

• Participation in another investigational drug trial within 4 weeks before enrollment.
• Non-epithelial ovarian cancer.
• Prior antineoplastic therapy (including chemotherapy, radiotherapy, targeted therapy, hormonal therapy, biologic therapy, immunotherapy, herbal medicine for antineoplastic purposes, or other investigational agents) within 28 days or 5 half-lives (whichever shorter) prior to first dose.
• Prior radiotherapy within 4 weeks prior to the first dose (including radiotherapy to >25% of bone marrow), or palliative localized radiotherapy to bone metastases within 2 weeks.
• Major surgery within 4 weeks prior to the first dose without complete recovery, or elective surgery planned during the trial.
• Other malignancies within the past 5 years (except stable breast cancer; except for adequately treated non-melanoma skin cancer or other solid tumors with no evidence of disease for >5 years).
• Any toxicity from prior therapy that has not recovered to baseline or to ≤ Grade 1 per NCI-CTCAE v6.0 prior to study treatment (except those posing no safety risk per investigator, e.g., alopecia).
• Symptomatic CNS or leptomeningeal metastases, or other evidence of uncontrolled CNS or leptomeningeal metastases, and deemed inappropriate for enrollment by investigator.
• HIV positive, HbsAg positive with HBV DNA > ULN (enrollment allowed if reduced to normal post-antiviral), Anti-HCV positive with HCV RNA positive, Tp-Ab positive.
• Active infection requiring systemic anti-infective therapy (per investigator).
• Pregnant or breastfeeding.
• Known history of drug/alcohol/substance abuse, definite prior history of neurological or psychiatric disorders.
• Presence of any active autoimmune disease, history of autoimmune disease or acquired immunodeficiency syndrome.
• Corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressants within 4 weeks prior to study drug, or requiring long-term systemic steroids during study (topical steroids allowed).
• Uncontrolled or significant cardiovascular disease, including severe/unstable angina pectoris, symptomatic congestive heart failure (NYHA II-IV), clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, or myocardial infarction within 6 months prior to the first dose.
• Poorly controlled hypertension despite antihypertensive therapy (i.e., SBP ≥150 mmHg and/or DBP ≥100 mmHg).
• Uncontrolled diabetes (defined as HbA1c ≥8%, or 7% ≤ HbA1c <8% with clinical symptoms of diabetes, such as polyuria, polydipsia, polyphagia, and weight loss) or other metabolic disorders, severe gastrointestinal bleeding, severe diarrhea (CTCAE ≥ Grade 2), or severe gastrointestinal obstruction requiring intervention.
• Pulmonary disease defined as ≥ Grade 3 per NCI-CTCAE v6.0, including dyspnea at rest, requirement for continuous oxygen therapy, or history of ILD.
• Known allergy to the investigational product or its major excipients, or kanamycin.
• History of thromboembolism, cerebral infarction, hemorrhagic disorders, or evidence of bleeding tendency within 6 months prior to the first dose.
• Any other concurrent severe and/or uncontrolled medical condition that, in the investigator's judgment, renders the patient unsuitable for participation.
• Female patients of childbearing potential unwilling to use effective contraception during the trial and for 6 months post-treatment. Pregnancy test required for patients with amenorrhea on antineoplastics, even if >12 months.
• Intestinal stoma or obstruction.
• Abdominal adhesions or infection precluding intraperitoneal drug administration.
• Physical condition unsuitable for intraperitoneal injection or other factors precluding study completion per investigator.

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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07462468 · WSKCT028

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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