Iparomlimab/Tuvonralimab + Standard Chemotherapy and Olaparib in Platinum-Sensitive Recurrent Ovarian Cancer

Официальное название

A Single-Arm, Exploratory, Multicenter Study Evaluating Iparomlimab/Tuvonralimab Combined With Standard Chemotherapy Followed by Olaparib in Platinum-Sensitive Recurrent Ovarian Cancer

Обзор

This is a prospective, open-label, single-arm, multicenter exploratory clinical study designed to evaluate the efficacy and safety of iparomlimab/tuvonralimab (QL1706), a bispecific antibody targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), in combination with standard platinum-based chemotherapy followed by olaparib in patients with platinum-sensitive recurrent epithelial ovarian cancer. Eligible participants are women aged 18-75 years with histologically or cytologically confirmed non-mucinous epithelial ovarian cancer (including serous carcinoma, clear cell carcinoma, endometrioid carcinoma, and carcinosarcoma) who experience first or second recurrence at least 6 months after the last platinum-containing chemotherapy, have measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and are deemed not suitable for surgery by the investigator. The study consists of a screening period (up to 28 days), a treatment period, and a follow-up period. Treatment is administered in 3-week cycles and continues until disease progression, unacceptable toxicity, withdrawal of consent, loss of clinical benefit per investigator judgment, completion of 2 years of iparomlimab/tuvonralimab (QL1706), or other protocol-defined reasons. Safety assessments are performed regularly during treatment; a safety follow-up visit is conducted 30 (±7) days after the last dose, and survival follow-up is performed every 2 months thereafter. The primary objective is to explore the antitumor efficacy of the regimen in platinum-sensitive recurrent epithelial ovarian cancer, and the secondary objective is to characterize the safety profile of the combination strategy.

Вмешательства

• Препарат Iparomlimab/Tuvonralimab
  Iparomlimab/Tuvonralimab administered intravenously in 3-week cycles per protocol

Первичные конечные точки

• Progression-Free Survival (PFS) [Срок оценки: Up to 24 months]

Критерии участия

Критерии включения

• Female participants aged 18 to 75 years. Voluntarily provide written informed consent and able to comply with protocol requirements.
• Histologically and/or cytologically confirmed recurrent non-mucinous epithelial ovarian cancer (including serous carcinoma, clear cell carcinoma, endometrioid carcinoma, and carcinosarcoma).
• First or second recurrence after standard platinum-containing chemotherapy, with recurrence diagnosed ≥ 6 months after the last dose of platinum-containing chemotherapy (platinum-sensitive recurrence).
• Not suitable for surgery as assessed by the investigator.
• At least one measurable lesion per RECIST v1.1.
• ECOG performance status 0-1.
• If no prior BRCA1/2 mutation test result is available, willing to provide tumor tissue and/or peripheral blood for confirmation of BRCA status (archival or fresh tumor tissue preferred; if re-biopsy poses safety risk, may be discussed with medical monitor).
• Prior exposure to PARP inhibitor(s) other than olaparib is allowed only if the prior PARPi exposure after first-line therapy was >18 months for BRCA-mutated participants or >12 months for BRCA wild-type participants, and recurrence occurred ≥12 months after the last PARPi dose.
• Estimated life expectancy ≥ 3 months.
• Adequate organ function: ANC ≥1.5×10\^9/L; platelets ≥100×10\^9/L; hemoglobin ≥90 g/L; serum albumin ≥30 g/L; TSH ≤1×ULN (if abnormal, FT3/FT4 within normal range); total bilirubin ≤1.5×ULN; AST/ALT ≤2.5×ULN (≤5×ULN if liver metastases); ALP ≤2.5×ULN; serum creatinine ≤1.5×ULN; INR ≤1.5 (if not on anticoagulation).
• Women of childbearing potential must have a negative serum/urine pregnancy test within 7 days prior to first dose, must not be breastfeeding, and must use medically accepted contraception during study treatment and for 3 months after the end of study treatment.

Критерии исключения

• Any active autoimmune disease or history of autoimmune disease.
• Mucinous ovarian cancer, sex cord-stromal tumors, or other non-eligible histologic types.
• Uncontrolled pleural effusion, pericardial effusion, or ascites that cannot be stabilized despite repeated drainage or other interventions per investigator judgment.
• Other active malignancy within 2 years prior to first dose.
• Central nervous system metastases or carcinomatous meningitis.
• Palliative radiotherapy or immunomodulatory agents (e.g., thymosin, interferon, IL-2) or antitumor Chinese patent medicines within 2 weeks prior to first dose; hormonal therapy within 1 week prior to first dose.
• Use of immunosuppressive agents or systemic corticosteroids for immunosuppression (prednisone >10 mg/day or equivalent) within 2 weeks prior to enrollment.
• Prior immuno-oncology therapies targeting tumor immunity (e.g., PD-1/PD-L1/CTLA-4 inhibitors, immune checkpoint agonists such as ICOS/CD40/CD137/GITR/OX40 antibodies, or immune cell therapy).
• Prior treatment with olaparib.
• Concomitant use of strong/moderate CYP3A inhibitors (washout 2 weeks) or strong/moderate CYP3A inducers (washout 5 weeks for enzalutamide/phenobarbital; 3 weeks for others).
• Major surgery, open biopsy, or significant traumatic injury within 4 weeks prior to first dose (except secondary cytoreductive surgery), or planned major elective surgery during the study.
• Live vaccine within 4 weeks prior to first dose or planned live vaccination during the study.
• Known primary or secondary immunodeficiency, including HIV antibody positive. Untreated chronic hepatitis B or HBV carrier with HBV DNA >1000 IU/mL; active hepatitis C.
• History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• History of interstitial lung disease or non-infectious pneumonitis.
• Serious infection within 4 weeks prior to first dose (e.g., sepsis, severe pneumonia, or infections requiring hospitalization).
• Active or clinically significant inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, chronic diarrhea requiring treatment).
• Severe cardiovascular or cerebrovascular disease/history.
• Peripheral neuropathy ≥ Grade 2 per NCI CTCAE v5.0.
• History of severe hypersensitivity reaction to other monoclonal antibodies. Pregnant or breastfeeding.
• Known allergy to any component of QL1706, olaparib, carboplatin, or paclitaxel formulations.
• Participation in another investigational drug/device study within 4 weeks prior to first dose.
• Any condition that, in the investigator's opinion, would increase risk with study treatment or interfere with study assessments or interpretation.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07454018 · 2026146

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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