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

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

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.

Inclusion Criteria:

1. Female participants aged 18 to 75 years. Voluntarily provide written informed consent and able to comply with protocol requirements.
2. Histologically and/or cytologically confirmed recurrent non-mucinous epithelial ovarian cancer (including serous carcinoma, clear cell carcinoma, endometrioid carcinoma, and carcinosarcoma).
3. 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).
4. Not suitable for surgery as assessed by the investigator.
5. At least one measurable lesion per RECIST v1.1.
6. ECOG performance status 0-1.
7. 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).
8. 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.
9. Estimated life expectancy ≥ 3 months.
10. 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).
11. 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.

Exclusion Criteria:

1. Any active autoimmune disease or history of autoimmune disease.
2. Mucinous ovarian cancer, sex cord-stromal tumors, or other non-eligible histologic types.
3. Uncontrolled pleural effusion, pericardial effusion, or ascites that cannot be stabilized despite repeated drainage or other interventions per investigator judgment.
4. Other active malignancy within 2 years prior to first dose.
5. Central nervous system metastases or carcinomatous meningitis.
6. 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.
7. Use of immunosuppressive agents or systemic corticosteroids for immunosuppression (prednisone >10 mg/day or equivalent) within 2 weeks prior to enrollment.
8. 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).
9. Prior treatment with olaparib.
10. 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).
11. 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.
12. Live vaccine within 4 weeks prior to first dose or planned live vaccination during the study.
13. 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.
14. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
15. History of interstitial lung disease or non-infectious pneumonitis.
16. Serious infection within 4 weeks prior to first dose (e.g., sepsis, severe pneumonia, or infections requiring hospitalization).
17. Active or clinically significant inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, chronic diarrhea requiring treatment).
18. Severe cardiovascular or cerebrovascular disease/history.
19. Peripheral neuropathy ≥ Grade 2 per NCI CTCAE v5.0.
20. History of severe hypersensitivity reaction to other monoclonal antibodies. Pregnant or breastfeeding.
21. Known allergy to any component of QL1706, olaparib, carboplatin, or paclitaxel formulations.
22. Participation in another investigational drug/device study within 4 weeks prior to first dose.
23. Any condition that, in the investigator's opinion, would increase risk with study treatment or interfere with study assessments or interpretation.