MIRV in Combination With Suvemcitug for Partially Platinum-Sensitive Ovarian Cancer (MISO)

Inclusion Criteria:

1. Signed written informed consent and able to comply with the protocol-specified visits and related procedures.

2. Female patients aged ≥18 years.

3. Patients with histologically or cytologically confirmed high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

4. Recurrence after prior standard platinum-based chemotherapy with or without bevacizumab ± PARP inhibitor, with the date of diagnosis of recurrence being 6-12 months from the last platinum-based chemotherapy.

5. Patients with a BRCA mutation must have received PARP inhibitor therapy.

6. Patients must have experienced disease progression during or after the most recent anticancer therapy received.

7. Tumor FRα expression has been determined by the VENTANA FOLR1 assay to be ≥25% (requiring ≥25% of tumor cells with staining intensity ≥2+ after FRα staining).

8. Patients must provide archived tumor tissue block or sections for central laboratory FRα testing and exploratory biomarker analysis. Tissue wax blocks are preferred; if wax blocks cannot be provided, no fewer than 10 unstained sections should be provided.

9. Patients must have at least one evaluable lesion per RECIST v1.1 (determined by the investigator via imaging).

10. Eastern Cooperative Oncology Group performance status (ECOG PS) must be 0-2.

11. Patients must have received at least 1 but no more than 2 lines of prior systemic anticancer chemotherapy:

    1. Neoadjuvant therapy ± adjuvant therapy is considered as 1 line of therapy;
    2. A change in treatment due to toxicity in the absence of disease progression is considered part of the same line of therapy (i.e., not counted separately).

12. Adequate major organ function, and the patient is considered by the investigator to be suitable for treatment with mirvetuximab soravtansine combined with suvemcitug, defined as:

    1. Absolute neutrophil count (ANC) ≥1.5 × 10^9/L (1,500/μL), and no use of G-CSF within the prior 10 days, or no use of long-acting WBC growth factors within the prior 20 days;
    2. Platelet count ≥100 × 10^9/L (100,000/μL) with no platelet transfusion within the prior 10 days;
    3. Hemoglobin ≥9.0 g/dL with no packed red blood cell (PRBC) transfusion within the prior 21 days;
    4. Serum creatinine ≤1.5 × upper limit of normal (ULN);
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × ULN;
    6. Serum bilirubin ≤1.5 × ULN (patients with Gilbert's syndrome may be enrolled if total bilirubin <3.0 × ULN);
    7. Serum albumin ≥2 g/dL.

13. All toxicities related to prior treatment (except alopecia) must have recovered to ≤ Grade 1 per CTCAE v5.0.

14. Any major surgery the patient has undergone must have been completed at least 4 weeks prior to the first dose of mirvetuximab soravtansine and suvemcitug, and postoperative complications from prior surgical treatment must have resolved or be stable.

15. The subject's life expectancy is assessed by the investigator to be at least 12 weeks.

Exclusion Criteria:

1. Concurrent participation in another clinical study.
2. Patients with endometrioid, clear cell, mucinous, or sarcoma histology, mixed tumors containing any of these histologies, or low-grade/borderline ovarian tumors.
3. Patients whom the investigator considers to have other serious systemic diseases (including active infection, non-infectious interstitial lung disease, clinically significant cardiovascular or cerebrovascular disease within 6 months prior to the first dose, etc.) or other reasons that make them unsuitable for participation in this clinical study.
4. Known prior hypersensitivity to monoclonal antibody therapy or maytansinoids, or to the study drug and/or any of its excipients.
5. Patients with active or chronic corneal disease, history of corneal transplant, or active eye disease requiring continuous treatment/monitoring, for example: uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injection therapy, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and/or monocular vision.
6. Patients with pleural effusion, pericardial effusion, or ascites that cannot be controlled by drainage or other methods should be excluded, except for small amounts of fluid that are asymptomatic or do not require clinical intervention.
7. Patients who have previously received mirvetuximab soravtansine or other FRα-targeted therapies.
8. Known active central nervous system (CNS) metastases and/or leptomeningeal disease. Subjects with untreated but asymptomatic brain metastases, or those with imaging evidence of sustained progression-free status for at least 4 weeks after treatment and no need for hormones or anti-epileptic therapy for at least 2 weeks, may be considered for enrollment.
9. Pregnant or breastfeeding women. Women of childbearing potential must agree to take highly effective contraceptive measures during the study drug period and for at least 7 months after the last dose of study drug. Women of childbearing potential are defined as fertile women from menarche until menopause, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
10. Patients who have received anti-tumor therapy or participated in a clinical study and received an investigational drug within 2 weeks prior to the first dose of this study.
11. Patients with hypertension that cannot be reduced to the normal range with antihypertensive medication (systolic blood pressure > 150 mmHg, diastolic blood pressure > 90 mmHg).
12. Patients with NYHA Class III-IV cardiac insufficiency, or left ventricular ejection fraction (LVEF) < 50% as indicated by echocardiography
13. Patients with proteinuria (urine protein > 1+ found during screening; or urine protein 1+ that does not return to normal upon repeat testing within 24 hours);
14. Patients with a clear tendency for gastrointestinal bleeding, including the following conditions: presence of a local active ulcer lesion with fecal occult blood (++) making them ineligible for enrollment; history of melena or hematemesis within 2 months; presence of high bleeding risk: Grade ≥ 3 bleeding events within the past 6 months, hemoptysis ≥ 2.5 mL per episode; imaging suggesting tumor erosion into major blood vessels; or investigator judgment that the bleeding risk is unacceptable;
15. Presence of high risk of gastrointestinal perforation/fistula: gastrointestinal perforation or active peptic ulcer within the past 6 months; or pelvic tumor significantly invading the bladder/rectum with potential risk of fistula (investigator judgment);
16. Coagulation abnormalities (INR > 1.5, APTT > 1.5 × ULN) with a bleeding tendency;
17. Long-term unhealed wounds or fractures; major surgery or severe traumatic injury, fracture, or ulcer within 4 weeks.