Liposomal Irinotecan Plus Enlonstobart for Platinum-Resistant Recurrent Ovarian Cancer

An Exploratory Clinical Study of Liposomal Irinotecan Combined With Enlonstobart in Patients With Platinum-Resistant Recurrent Ovarian Cancer

This is a prospective, single-center, single-arm exploratory clinical study designed to evaluate the efficacy and safety of liposomal irinotecan combined with enlonstobart in patients with platinum-resistant recurrent ovarian cancer.

Eligible female participants with histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, FIGO stage II-IV, will receive liposomal irinotecan and enlonstobart every 2 weeks. Tumor assessment will be performed every 8 weeks. Participants may discontinue study treatment in the event of disease progression, intolerable toxicity, withdrawal of consent, or other reasons judged by the investigator.

Ovarian cancer is one of the most common gynecologic malignancies and has the highest mortality among gynecologic cancers. Most patients are diagnosed at an advanced stage, and recurrence is common after standard surgery and platinum-taxane-based chemotherapy. For patients with platinum-resistant recurrent ovarian cancer, treatment options remain limited and new therapeutic strategies are needed.

Irinotecan is a topoisomerase I inhibitor with antitumor activity in ovarian cancer. Liposomal irinotecan is a liposomal formulation designed to prolong circulation time, increase tumor drug accumulation, and reduce systemic toxicity compared with conventional irinotecan. Immune checkpoint inhibitors have shown activity in selected tumor types, and preclinical and clinical evidence suggests that irinotecan may enhance the effect of anti-PD-1 therapy. Enlonstobart is an anti-PD-1 monoclonal antibody.

This exploratory study will evaluate the objective response rate, progression-free survival, overall survival, and safety of liposomal irinotecan combined with enlonstobart in patients with platinum-resistant recurrent ovarian cancer receiving second- to fourth-line treatment.

Inclusion Criteria:

1. Female participants aged 18 to 75 years, inclusive, at the time of signing informed consent.

2. Histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, FIGO stage II-IV.

3. Platinum-resistant recurrent disease, defined as disease progression within 6 months after the last platinum-containing chemotherapy, and not platinum-refractory disease, defined as disease progression within 4 weeks after initial platinum-containing chemotherapy. Participants may have received up to two prior lines of non-platinum systemic therapy. Treatment with a PARP inhibitor or anti-angiogenic therapy after platinum-resistant recurrence will be counted as one line of therapy; maintenance treatment with a PARP inhibitor or anti-angiogenic therapy will not be counted as a treatment line.

4. Ability to provide sufficient qualified formalin-fixed paraffin-embedded tumor tissue samples or slides for PD-L1 testing. Participants who are unable to provide tumor tissue slides for certain reasons may be enrolled at the investigator's discretion.

5. At least one measurable lesion at baseline according to RECIST version 1.1. The measurable lesion must not have received prior local therapy such as radiotherapy. A lesion located within a previously irradiated area may be selected as a target lesion if disease progression has been confirmed.

6. ECOG performance status of 0 or 1.

7. Expected survival of at least 3 months.

8. Adequate organ function, meeting all of the following criteria without blood transfusion, hematopoietic stimulating factors, or medication correction of blood cell counts within 14 days before the first dose:

   1. Absolute neutrophil count ≥1.5 × 10^9/L;
   2. Platelet count ≥75 × 10^9/L;
   3. Hemoglobin ≥9 g/dL;
   4. Serum creatinine ≤1.5 × the upper limit of normal or creatinine clearance ≥50 mL/min;
   5. Total bilirubin ≤1.5 × the upper limit of normal, or ≤3 × the upper limit of normal for participants with Gilbert's syndrome;
   6. Alanine aminotransferase and aspartate aminotransferase ≤2.5 × the upper limit of normal, or ≤5 × the upper limit of normal for participants with liver metastases;
   7. Activated partial thromboplastin time and international normalized ratio ≤1.5 × the upper limit of normal, without anticoagulants or other drugs affecting coagulation function within 14 days before the first dose, except for participants requiring long-term anticoagulation due to underlying disease.

9. Toxicities caused by prior antitumor therapy must have recovered to Grade 1 or lower according to CTCAE version 5.0, except for residual alopecia and fatigue.

10. Participants must understand the study and voluntarily sign written informed consent before study entry.

Exclusion Criteria:

1. History of severe hypersensitivity reaction to monoclonal antibody preparations or uncontrolled allergic asthma.
2. Known untreated central nervous system metastases, or treated but still symptomatic central nervous system metastases. Participants with residual signs or symptoms related to central nervous system treatment may be eligible if neurological symptoms have been stable or improved for at least 2 weeks before screening.
3. History of primary immunodeficiency.
4. Active autoimmune disease or history of autoimmune disease. Participants with well-controlled type 1 diabetes mellitus, well-controlled hypothyroidism requiring only hormone replacement therapy, skin diseases not requiring systemic treatment such as vitiligo, psoriasis, or alopecia, or conditions not expected to recur without external triggers may be eligible for further screening.
5. Serious arterial or venous thrombotic events within 3 months before screening, such as transient ischemic attack, cerebral hemorrhage, cerebral infarction, deep venous thrombosis, or pulmonary embolism.
6. History of interstitial lung disease, except localized radiation-induced interstitial pneumonia, or noninfectious pneumonia requiring glucocorticoid therapy.
7. Prior treatment with any antibody or drug targeting T-cell costimulatory or immune checkpoint pathways, including PD-1, PD-L1, PD-L2, CTLA-4, OX40, or CD137 inhibitors.
8. Prior immune-related adverse event of CTCAE version 5.0 Grade 3 or higher after immunotherapy.
9. Major surgery or radical radiotherapy within 28 days before the first dose; palliative radiotherapy within 14 days before the first dose; or use of radiopharmaceuticals such as strontium or samarium within 56 days before the first dose.
10. Systemic antitumor therapy within 28 days before the first dose, including but not limited to chemotherapy, immunotherapy, macromolecular targeted therapy, or biological therapy such as tumor vaccines, cytokines, or growth factors used to control cancer. Small-molecule targeted therapy or oral fluoropyrimidines within 14 days before the first dose or within 5 half-lives, whichever is longer; or mitomycin C or nitrosoureas within 6 weeks before the first dose.
11. Receipt of a live attenuated vaccine within 28 days before the first dose or planned receipt of a live attenuated vaccine during the study.
12. Any active infection requiring systemic treatment by intravenous infusion within 28 days before the first dose.
13. Treatment within 14 days before the first dose with traditional Chinese patent medicines approved by the NMPA whose package inserts clearly state antitumor indications, or traditional Chinese herbal medicine documented in the medical record as being used for antitumor purposes.
14. Whole blood or blood component transfusion within 14 days before the first dose.
15. Treatment with glucocorticoids equivalent to prednisone >10 mg/day or other immunosuppressive agents within 14 days before the first dose.
16. Participation in another clinical trial and receipt of investigational treatment within 28 days before the first dose, calculated from the date of the last treatment in the previous clinical study, except participation in overall survival follow-up of a study.
17. Positive human immunodeficiency virus antibody or Treponema pallidum antibody; positive hepatitis B surface antigen and/or hepatitis B core antibody with hepatitis B virus DNA above the upper limit of normal of the testing laboratory; or positive hepatitis C antibody with hepatitis C virus RNA above the upper limit of normal of the testing laboratory.
18. History of active tuberculosis.
19. Pregnancy or breastfeeding.
20. Other malignancy that progressed or required treatment within 5 years before screening, except adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or cured carcinoma in situ such as breast carcinoma in situ.
21. Any other condition that may increase the risk associated with study treatment, interfere with interpretation of study results, affect study compliance, or otherwise make the participant unsuitable for the study in the investigator's judgment.
22. Any clinically significant gastrointestinal disease, including liver disease, bleeding, inflammation, obstruction, or diarrhea greater than Grade 2.
23. Current use or use within the past 2 weeks of strong CYP3A enzyme inducers or inhibitors and/or strong UGT1A inhibitors.
24. Prior use of liposomal irinotecan formulation or irinotecan.
25. Any condition that, in the investigator's judgment, makes the participant unsuitable for this study.