A Single-arm Clinical Trial of IMGN853 in Chinese Adult Patients With Platinum-resistant, Epithelial Ovarian Cancer

Inclusion Criteria:

1. Female patients ≥ 18 years of age
2. Patients must have a histopathologically confirmed diagnosis of high-grade serous EOC.
3. Patients must have platinum-resistant disease:
4. Patients must have had a response (CR or PR) after previous 1 line ofplatinum-based therapy for at least 4 cycles of treatment, and then progressedbetween > 3 months and ≤ 6 months after the date for last dose of platinum.
5. Patients who relapsed after > 6 months since the last platinum-based treatmentwith at least 4 cycles of one line platinum-based therapy: 1) continued toreceive at least 4 cycles of 2 or 3 lines of platinum-based treatment and musthave had PD within 6 months from the last dose of platinum; or 2) had PD duringtreatment with 2 or 3 lines of platinum-containing chemotherapy. Note: PD should be calculated from the date of the last dose of platinum-containingtherapy to the date of PD indicated by radiographic imaging. Note: Patients who are platinum-refractory during 1 line treatment are excluded (seeexclusion criterion 3).
6. Patients must have radiological PD on or after the most recent anti-cancer therapy.
7. Patients must be willing to provide the archival tumor tissue slides or undergolow-risk routine medical procedures to collect new biopsy samples forimmunohistochemistry (IHC) confirmation of FRα positivity.
8. Per VENTANA FOLR1 (FOLR-2.1) Assay criteria, patient's tumor must be positive for FRαexpression by a central laboratory.
9. Patients must have at least one lesion that meets the definition of measurable diseaseby RECIST v1.1 (radiologically assessed by the investigator).
10. Patients must have received at least 1 but no more than 3 lines of prior systemicanti-cancer therapy, including at least 1 line of therapy containing bevacizumab, andfor whom monotherapy is appropriate for the next line of treatment:
11. Neoadjuvant ± adjuvant is considered as 1 line of therapy;
12. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as partof the prior line of therapy (ie, not counted independently);
13. Therapy changed due to toxicity in the absence of PD will be considered as partof the same line (ie, not counted independently);
14. Hormonal therapy (except as maintenance therapy) will be considered as a separateline of therapy.
15. Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS)of 0 or 1.
16. Patients must have completed prior therapy within the following specified times:
17. Systemic anti-tumor therapy (the last prior systemic anti-tumor therapy should beat least 5 half-lives or 4 weeks from the initiation of the investigational drug,whichever is shorter);
18. Focal radiotherapy: previous focal radiotherapy should be at least 2 weeks fromthe initiation of investigational drug.
19. All toxicities (except alopecia) associated with prior therapy must be stable orresolved (Grade 1 or normal).
20. Any major surgery that a patient has undergone must have been completed at least 4weeks prior to the first dose of IMGN853 and the postoperative complications of priorsurgical treatment have resolved or are stable.
21. Patients must have adequate hematologic, hepatic, and renal functions as defined bythe following parameters (without G-CSF [a 20-day drug washout period for long-actinggrowth factors], human albumin injection and other corrective treatment drugs are notallowed within 14 days before obtaining laboratory test values):
22. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L (1,500 μL);
23. Platelet count ≥ 100 × 10^9/L (100,000/μL) without platelet transfusion in theprior 10 days;
24. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in theprior 21 days;
25. Serum creatinine ≤ 1.5 × upper limit of normal (ULN);
26. Both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 ×ULN;
27. Serum bilirubin ≤ 1.5 × ULN (patients with Gilbert syndrome may be enrolled iftotal bilirubin is < 3.0 × ULN);
28. Serum albumin ≥ 2 g/dL.
29. Patients or their legally authorized representatives must be willing and able to signthe ICF and comply with the requirements of the protocol.
30. Women of child bearing potential (WCBP), defined as a sexually mature woman who havenot undergone surgical sterilization or who have not been naturally postmenopausal forat least 12 consecutive months (ie, who have had menses any time in the preceding 12consecutive months) must agree to use effective contraceptive methods; examplesincluded oral, parenteral, or implantable hormonal contraceptive, intrauterine device,barrier contraceptive with spermicide, partner's latex condom or vasectomy) while onstudy treatment and for at least 12 weeks after the last dose of investigational drug.
31. WCBP must have a negative pregnancy test within 4 days prior to the first dose ofIMGN853.
32. The expected survival of the subject is at least 12 weeks as assessed by theinvestigator.

Exclusion Criteria:

1. Male patients.
2. Patients with endometrioid carcinoma, clear cell carcinoma, mucinous carcinoma, orsarcoma tissue, mixed tumor containing any of the above histologies, or lowgrade/borderline ovarian tumor.
3. Patients with primary platinum-refractory disease, defined as disease that did notrespond to (CR or PR) or has progressed within 3 months of the last dose of first-lineplatinum-containing chemotherapy.
4. Patients who have received prior wide-field radiotherapy (RT) with at least 20% of thebone marrow affected.
5. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria forAdverse Events (CTCAE).
6. Patients with active or chronic corneal disorders, history of corneal transplant, oractive ocular conditions requiring ongoing treatment/monitoring such as uncontrolledglaucoma, wet age-related macular degeneration requiring treatment with intravitrealinjections, active diabetic retinopathy with macular edema, macular degeneration,presence of papilloedema, and /or monocular vision.
7. Patients with serious concurrent illness or clinically relevant active infection,including, but not limited to the following:
8. Known acute or chronic active hepatitis B (HBsAg positive and HBV DNA viral load ≥ 2500 copies/mL or > 500 IU/mL, if necessary, patients may receive nucleosideprophylactic anti-hepatitis B virus therapy) or acute or chronic active hepatitisC (HCV antibody positive and HCV RNA positive);
9. Human immunodeficiency virus (HIV) infection;
10. Active cytomegalovirus infection;
11. Any other concurrent infectious disease requiring systematic treatment within 2weeks prior to the first dose of IMGN853.
12. Patients with a history of multiple sclerosis (MS) or other demyelinating diseasesand/or Lambert-Eaton syndrome (paraneoplastic syndrome).
13. Patients with clinically significant cardiac disorders, including but not limited toany of the following:
14. Myocardial infarction ≤ 6 months prior to the first dose;
15. Unstable angina pectoris;
16. Uncontrolled congestive cardiac failure (New York Heart Associationclassification > II);
17. Uncontrolled ≥ Grade 3 hypertension (per CTCAE criteria);
18. Uncontrolled cardiac arrhythmias.
19. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior tosigning the ICF.
20. Patients with a history of hepatic cirrhosis (Child-Pugh B or C).
21. Patients with a previous clinical diagnosis of or currently ongoing non-infectiousinterstitial lung disease (ILD), including noninfectious pneumonitis, lung disorderssuch as pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-relatedpulmonitis, severely impaired lung function, etc.
22. Patients requiring folic acid-containing supplements (e.g., folate deficiency).
23. Known hypersensitivity to previous monoclonal antibody therapy or maytansinoids, or tothe investigational drug and/or any excipients.
24. Pregnant or lactating women.
25. Patients with prior IMGN853 or other FRα-targeted drug therapies.
26. Known active central nervous system (CNS) and/or leptomeningeal metastases. Patientswith untreated but asymptomatic brain metastases, or patients who haveradiographically documented progression-free status for at least 4 weeks aftertreatment and do not require hormonal or antiepileptic therapy for at least 2 weeksmay be considered for enrollment.
27. Patients with a history of other malignancies within 3 years prior to enrollment. Note: patients with tumors with a negligible risk of metastasis or death (e.g.,adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, orcarcinoma in situ of the cervix or breast) are eligible for inclusion.
28. Patients with pleural effusion, pericardial effusion, or ascites that cannot becontrolled by drainage or other means, except the small amount of effusion thatwithout clinical symptoms or do not require clinical intervention.
29. Patients who are detained by a court or administrative decision, receiving psychiatriccare against their will, adults who are under the protection of law (undertutorship/curatorship), people who are unable to give their consent, and people whoare subject to a legal guardianship.
30. Participated in other clinical studies and received their investigational drugs within 4 weeks prior to the first dose.
31. Subject has other serious systemic diseases or other reasons that are not suitable forparticipation in this clinical study as evaluated by the investigator.