The primary objectives of the study are: (1) in the dose-escalation part: to evaluate safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of farletuzumab ecteribulin (MORAb-202) in participants with selected tumor types (ovarian cancer \[OC\], endometrial cancer \[EC\], non-small cell lung carcinoma \[NSCLC\], triple-negative breast cancer \[TNBC\]), and (2) in dose-confirmation part: to evaluate preliminary efficacy measured by objective response rate (ORR) of farletuzumab ecteribulin (MORAb-202) in participants with OC and EC at selected doses and to further evaluate the safety and tolerability of farletuzumab ecteribulin (MORAb-202) and (3) dose-optimization part. (divided in two parts: Part A \[OC and EC participants\] and Part B \[OC only\]): Part A: to evaluate other farletuzumab ecteribulin (MORAb-202) treatment regimens for safety, tolerability and preliminary efficacy in participants with OC and EC; to evaluate the addition of short course of oral corticosteroids following every dose of farletuzumab ecteribulin (MORAb-202) administered every 21 days; and to select treatment regimens with farletuzumab ecteribulin (MORAb-202) for further evaluation in Part B. Part B: to evaluate the safety and tolerability of different doses of farletuzumab ecteribulin (MORAb-202) as monotherapy and in combination with lenvatinib and to determine the recommended dose (RD) of farletuzumab ecteribulin (MORAb-202) as monotherapy and in combination with lenvatinib.
Aged >=18 years
TNBC: Histologically confirmed diagnosis of metastatic TNBC (that is, estrogen receptor (ER) negative/progesterone receptor negative/ human epidermal growth factor receptor 2 (HER2) negative (defined as immunohistochemistry (IHC) less than (<) 2 plus (+) or fluorescence in situ hybridization (FISH) negative) breast cancer). Previously treated with at least one line of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting.
NSCLC adenocarcinoma: Histologically or cytologically confirmed metastatic NSCLC adenocarcinoma: participants who have failed previous treatment for metastatic disease, are not indicated or failed epidermal growth factor receptor (EGFR)-, Anaplastic lymphoma kinase (ALK) -, B-Raf proto-oncogene (BRAF) - or c-ros oncogene 1 (ROS1) - targeted therapy, and for whom no alternative standard therapy exists.
EC: Histologically confirmed diagnosis of advanced, recurrent or metastatic EC. Relapsed or failure of at least one platinum-based regimen or one immunotherapy-based regimen.
Participants with endometrial leiomyosarcoma, endometrial stromal sarcoma or other soft tissue sarcoma histology.
Participants who received previous treatment with any folate receptor targeting agents, except for mirvetuximab soravtansine in the setting of FRA >=75%.
Participants with platinum refractory ovarian cancer (defined as disease progression during the initial platinum-based chemotherapy treatment).
Currently enrolled in another clinical study or used any investigational drug or device, which in the opinion of the Sponsor may interfere with the study treatment, within the past 28 days or 5 times the half-life (where prior drug therapy falls under the parameters these Inclusion Criteria should be followed) of any investigational drug preceding informed consent.
Sequential
Farletuzumab ecteribulin
DrugFarletuzumab ecteribulin intravenous infusion.
Prednisone
DrugPrednisone administered orally.
Prednisolone
DrugPrednisolone administered orally.
Dexamethasone
DrugDexamethasone administered orally.
Lenvatinib
DrugLenvatinib administered orally.
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Treatment groupsSee each treatment group below.
Dose Escalation Part: Recommended Phase 2 Dose (RP2D) of Farletuzumab Ecteribulin
Dose Optimization Part B: Recommended Dose (RD) of Farletuzumab Ecteribulin Monotherapy and in Combination With Lenvatinib
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), based on the investigator assessment of radiologic response according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Number of Participants With Dose-limiting Toxicities (DLTs)
DLTs are any of the toxicities occurring during Cycle 1 and assessed by the investigator as related to study drug. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).
Duration of Response (DOR)
DOR is defined as the time from the first date of documented CR or PR to the date of disease progression or death, whichever occurs first. It will be calculated for participants whose BOR is CR or PR. DOR will be assessed according to RECIST version 1.1.
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD). DCR will be assessed according to RECIST version 1.1.
Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants with BOR of CR, PR, or durable SD (duration of SD greater than or equal to \[\>=\] 5 weeks). Duration of SD is defined as the time from the date of first dose to the date of the first documentation of disease progression or death, whichever occurs first. It will be calculated for participants whose BOR is SD. CBR will be assessed according to RECIST version 1.1.
Progression Free Survival (PFS)
PFS is defined as the time from the date of first dose to the date of the first documentation of disease progression or death, whichever occurs first. PFS will be assessed according to RECIST version 1.1.
