Ovarian cancer , Endometrial cancer, NSCLC, Triple negative breast
Conditions
Interventions
Dose Escalation Part:
Participants with selected tumor types will receive farletuzumab ecteribulin (MORAb-202) as an intravenous infusion on Day 1 of a 21-day cycle.
Dose Confirmation Part:
Particip
Sponsors
Suzuki Takuya
Eligibility
Inclusion criteria
Inclusion criteria: 1.Aged >=18 years 2.For Dose-Escalation:Females (TNBC, EC and OC) or males/females (NSCLC, adenocarcinoma). Participants with the following disease characteristics: Participants with the following tumor types, each as a separate arm: a.TNBC:Histologically confirmed diagnosis of metastatic TNBC. Previously treated with at least one line of systemic anticancer therapy (cytotoxic or targeted anticancer agents) in the metastatic setting. b.NSCLC adenocarcinoma: Histologically or cytologically confirmed metastatic NSCLC adenocarcinoma: participants who have failed previous treatment for metastatic disease, are not indicated or failed EGFR-, ALK-, BRAF- or ROS1-targeted therapy, and for whom no alternative standard therapy exists. c.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. d.OC or primary peritoneal or fallopian tube cancer: Histologically confirmed diagnosis of high grade serous (HGS) epithelial ovarian cancer or primary peritoneal cancer or fallopian tube cancer. Participants must have: -platinum-resistant disease (defined as progression within 6 months after the last dose of at least 4 cycles of the last platinum containing chemotherapy regimen) -received up to 4 lines of systemic therapy post development of platinum resistance. For Dose-Confirmation and Dose Optimization: Note:Only participants with histologically confirmed diagnosis of advanced, recurrent, or metastatic EC will be enrolled at sites in France. HGS ovarian cancer or primary peritoneal cancer or fallopian tube cancer: -Platinum-resistant disease: -For participant with 1 line of platinum-containing therapy: progression > 1 month and <= 6 months after the last dose of the first platinum-containing therapy regimen (of at least 4 cycles) -For participant with 2-3 lines of platinum-containing therapy: progression during or within 6 months after the last dose of the 2nd or 3rd platinum-containing therapy regimen. -Have received up to 3 prior lines of systemic therapy and for whom single-agent therapy is appropriate as the next line of therapy. Participants may have been treated with up to one line of therapy subsequent to determination of platinum-resistance. In Dose Optimization Part B (DOPB) participants may have received up to 3 prior lines of systemic therapy, up to 4 prior lines is permitted for participants who have received prior mirvetuximab soravtansine (MIRV) -Neoadjuvant +/- adjuvant will be considered 1 line of therapy. -Maintenance therapy will be considered part of the preceding line of therapy (will not be counted as an independent line of therapy). -Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance. -Therapy changed due to toxicity in the absence of progression will be considered part of the same line. EC (not enrolled in DOPB): -Participants must have histologically confirmed diagnosis of advanced, recurrent, or metastatic EC. All histologic (including carcinosarcoma [no more than one participant at any dose level]) and molecular subtypes will be included. Participants may have been treated with an ICI containing regimen (or be ineligible for ICI treatment) and must have had no more than 2 prior regimens (not including adjuvant therapy if progression or recurrent/metastatic disease occurred more than 6 months after the completion of the last cycle of adjuvant therapy). -Note: There is
Exclusion criteria
Exclusion criteria: 1. Endometrial leiomyosarcoma, endometrial stromal sarcoma or other soft tissue sarcoma histology. 2. Received previous treatment with any folate receptor targeting agents, except for MIRV in the setting of FRA >=75%. 3. Platinum refractory ovarian cancer (defined as disease progression during the initial platinum-based chemotherapy treatment). 4. 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 of any investigational drug preceding informed consent. 5. Participants with brain or subdural metastases are not eligible. Brain metastases must be stable for at least 4 weeks on 2 consecutive scans of the brain before starting study treatment. 6. Diagnosed with meningeal carcinomatosis. 7. Any other invasive malignancy that required treatment or has shown evidence of recurrence/progression during the 2 years prior to starting study treatment. 8. Significant cardiovascular impairment. History within 6 months prior to the first dose of study drug of: congestive heart failure greater than NYHA Class II); unstable angina; myocardial infarction; stroke; cardiac arrhythmia associated with hemodynamic instability. In addition, for participants enrolled in the MORAb-202 plus Lenvatinib cohorts, significant cardiovascular impairment also includes: History of arterial thromboembolism within 12 months of starting study treatment; LVEF 480 ms. 10. Known to be HIV positive. Testing at entry not required. 11. Active viral hepatitis (B or C as demonstrated by positive serology). 12. Females who are breastfeeding or pregnant at Screening or Baseline with a minimum sensitivity of 25 IU/L or equivalent units of bhCG [or hCG]. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first administration of the study drug. 13. Females of childbearing potential who - within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following: - total abstinence (if it is their preferred and usual lifestyle)* - an intrauterine device or IUS - a contraceptive implant - combined hormonal contraception associated with inhibition of ovulation or progestogen-only hormonal contraception associated with inhibition of ovulation. Participants using an oral contraceptive (participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 7 months (5*half-life plus 180 days) after study drug discontinuation) - bilateral tubal occlusion - have a vasectomized partner with confirmed azoospermia - do not agree to use a highly effective method of contraception throughout the entire study period and for 7 months (5*half-life plus 180 days) after study drug discontinuation. For sites outside of the EU, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Dose Escalation Part: Recommended Phase 2 Dose (RP2D) of Farletuzumab Ecteribulin [Time Frame: Cycle 1 (Cycle length is equal to [=] 21 days)] 2. Dose Optimization Part B: Recommended Dose (RD) of Farletuzumab Ecteribulin Monotherapy and in Combination With Lenvatinib [Time Frame: Up to approximately 5 years] 3. 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. [Time Frame: From date of first dose of study drug until first documentation of CR or PR (up to approximately 24 weeks)] 4. 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). [Time Frame: Cycle 1 (Cycle length=21 days)] 5. Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Treatment Discontinuation and Adverse Events of Interest (AEIs) AE: as any untoward medical occurrence in a participant administered with an investigational product. SAE: as any untoward medical occurrence that at any dose; resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in congenital anomaly/birth defect. AEIs are AEs that may be associated with the use of immunomodulatory drugs, such as infections, malignancies, autoimmune disorders, and injection reactions. Number of participants with AEIs were reported based on safety assessment of participants with interstitial lung disease (ILD), severity of ILD, time to resolution and onset of ILD sympt | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. 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. [Time Frame: From first documented CR or PR until first documentation of recurrent or progressive disease or death (up to approximately 5 years)] 2. 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. [Time Frame: From first dose of study drug until first documentation of CR or PR or SD (up to approximately 5 years)] 3. 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. [Time Frame: From first dose of study drug until disease progression or death, whichever occurs first (up to approximately 5 years)] 4. 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. [Time Frame: From first dose of study drug until disease progression, death, whichever occurs first (up to approximately 5 years)] 5. Overall Survival (OS) OS is defined as the time from the date of first dose to the date of death. For the participants who are alive or lost to follow up, OS is censored as the date of last known alive date or the date of data cutoff, whichever comes first. OS will be calculated using the Kaplan-Meier method. [Time Frame: Fro | — |
Countries
France, Japan, Spain, UK, US
Contacts
Public ContactInquiry service
Eisai Co., Ltd.
Outcome results
None listed