A Study to Evaluate the Safety, Tolerability, and Efficacy of MORAb-202 (Herein Referred to as Farletuzumab Ecteribulin), a Folate Receptor Alpha (FRα)-Targeting Antibody-drug Conjugate (ADC) in Participants With Selected Tumor Types

NCT04300556 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MORAb-202-G000-2012019-003600-122023-506868-14
• Study Type: interventional
• Target: 182
• Locations: 5 countries
• Sites: 58

Brief Summary

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.

Conditions

Solid Tumor

Keywords

Lenvatinib; Farletuzumab ecteribulin; Neoplasms; Endometrial Neoplasms; Triple-Negative Breast Cancer; Endometrial Carcinoma; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Ovarian Neoplasms; Folate Receptor Alpha (FRA)

Outcome Measures

Primary Outcomes (5)

• Dose Escalation Part: Recommended Phase 2 Dose (RP2D) of Farletuzumab Ecteribulin

  Cycle 1 (Cycle length is equal to [=] 21 days)

• Dose Optimization Part B: Recommended Dose (RD) of Farletuzumab Ecteribulin Monotherapy and in Combination With Lenvatinib

  Up to approximately 5 years

• 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.

  From date of first dose of study drug until first documentation of CR or PR (up to approximately 24 weeks)

• 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).

  Cycle 1 (Cycle length=21 days)

• 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 incongenital 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 symptoms and deaths due to ILD.

  Baseline up to 28 days after the last dose of study drug (up to approximately 5 years)

Secondary Outcomes (14)

• Duration of Response (DOR)

  From first documented CR or PR until first documentation of recurrent or progressive disease or death (up to approximately 5 years)

• Disease Control Rate (DCR)

  From first dose of study drug until first documentation of CR or PR or SD (up to approximately 5 years)

• Clinical Benefit Rate (CBR)

  From first dose of study drug until disease progression or death, whichever occurs first (up to approximately 5 years)

• Progression Free Survival (PFS)

  From first dose of study drug until disease progression, death, whichever occurs first (up to approximately 5 years)

• Overall Survival (OS)

  From first dose of study drug until death (up to approximately 5 years)

Study Arms (6)

Dose Escalation Part: Farletuzumab ecteribulin

EXPERIMENTAL

Participants with selected tumor types will receive farletuzumab ecteribulin (MORAb-202) as an intravenous infusion, once every 3 weeks in a 21-day cycle.

Drug: Farletuzumab ecteribulin

Dose Confirmation Part: Farletuzumab ecteribulin

EXPERIMENTAL

Participants with EC and OC will receive farletuzumab ecteribulin (MORAb-202) as an intravenous infusion, once every 3 weeks in a 21-day cycle.

Drug: Farletuzumab ecteribulin

Dose Optimization Part A, Cohort 1: Farletuzumab ecteribulin + Oral Corticosteroids

EXPERIMENTAL

Participants with EC and OC will receive farletuzumab ecteribulin (MORAb-202) as an intravenous infusion and oral corticosteroids in a 21-day cycle.

Drug: Farletuzumab ecteribulin; Drug: Prednisone; Drug: Prednisolone; Drug: Dexamethasone

Dose Optimization Part A, Cohort 2: Farletuzumab ecteribulin

EXPERIMENTAL

Participants with EC and OC will receive farletuzumab ecteribulin (MORAb-202) as an intravenous infusion on three different days in a 21-day cycle.

Drug: Farletuzumab ecteribulin

Dose Optimization Part A, Cohort 3: Farletuzumab ecteribulin

EXPERIMENTAL

Participants with EC and OC will receive farletuzumab ecteribulin (MORAb-202) as an intravenous infusion on two different days in a 21-day cycle.

Drug: Farletuzumab ecteribulin

Dose Optimization Part B: Farletuzumab ecteribulin + Lenvatinib

EXPERIMENTAL

Participants with OC will either receive farletuzumab ecteribulin (MORAb-202) monotherapy as an intravenous infusion or in combination with lenvatinib, orally in a 21-day cycle.

Drug: Farletuzumab ecteribulin; Drug: Lenvatinib

Interventions

Farletuzumab ecteribulin DRUG

Farletuzumab ecteribulin intravenous infusion.

Also known as: MORAb-202

Dose Confirmation Part: Farletuzumab ecteribulin; Dose Escalation Part: Farletuzumab ecteribulin; Dose Optimization Part A, Cohort 1: Farletuzumab ecteribulin + Oral Corticosteroids; Dose Optimization Part A, Cohort 2: Farletuzumab ecteribulin; Dose Optimization Part A, Cohort 3: Farletuzumab ecteribulin; Dose Optimization Part B: Farletuzumab ecteribulin + Lenvatinib

Prednisone DRUG

Prednisone administered orally.

Dose Optimization Part A, Cohort 1: Farletuzumab ecteribulin + Oral Corticosteroids

Prednisolone DRUG

Prednisolone administered orally.

Dose Optimization Part A, Cohort 1: Farletuzumab ecteribulin + Oral Corticosteroids

Dexamethasone DRUG

Dexamethasone administered orally.

Dose Optimization Part A, Cohort 1: Farletuzumab ecteribulin + Oral Corticosteroids

Lenvatinib DRUG

Lenvatinib administered orally.

Dose Optimization Part B: Farletuzumab ecteribulin + Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged \>=18 years
• 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:
• 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.
• OC or primary peritoneal cancer or fallopian tube cancer: Histologically confirmed diagnosis of high grade serous 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.
• High-grade serous ovarian cancer or primary peritoneal cancer or fallopian tube cancer:
• Platinum-resistant disease:
• For participant with 1 line of platinum-containing therapy: progression greater than (\>) 1 month and less than or equal to (\<=) 6 months after the last dose of the first platinum-containing chemotherapy regimen (of at least 4 cycles)

You may not qualify if:

• 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).
• Participants with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 2 weeks before starting treatment in this study. Brain metastases must be stable for at least 4 weeks on 2 consecutive scans of the brain before starting study treatment.
• Diagnosed with meningeal carcinomatosis.
• Any other invasive malignancy that required treatment (other than definitive surgery) or has shown evidence of recurrence/progression (except for non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ) during the 2 years prior to starting study treatment.
• Significant cardiovascular impairment. History within 6 months prior to the first dose of study drug of: congestive heart failure greater than New York Heart Association (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; Left ventricular ejection fraction (LVEF) \<50% or below the institutional normal range determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).Note: Medically controlled arrhythmia is permitted.
• Clinically significant ECG abnormality, including marked prolonged baseline QT as corrected using Fridericia's formula (QTcF) (repeated demonstration of a QTcF interval \>500 milliseconds \[ms\]). A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolong the QTcF.
• For participants enrolled in the MORAb-202 plus lenvatinib cohorts, prolongation of the QTcF interval to \>480 ms.
• Known to be Human Immunodeficiency Virus (HIV) positive. Testing at entry not required.
• Active viral hepatitis (B or C as demonstrated by positive serology). Testing at entry if there are no symptoms or history is not required unless as per local requirements.
• Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta human chorionic gonadotropin \[ß-hCG\] or human chorionic gonadotropin \[hCG\]) with a minimum sensitivity of 25 International units per liter (IU/L) or equivalent units of ß-hCG \[or hCG\]. 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.
• 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:

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (58)

ACRC/Arizona Clinical Research Center, Inc

Tucson, Arizona, 85715, United States

WITHDRAWN

Universty of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

COMPLETED

Stanford Women's Cancer Center

Palo Alto, California, 94304, United States

RECRUITING

University of Miami

Coral Gables, Florida, 33146, United States

COMPLETED

Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

RECRUITING

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

COMPLETED

Georgia Cancer Center

Augusta, Georgia, 30912, United States

RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Ascension Illinois-Skokie Infustion Center

Skokie, Illinois, 60077, United States

WITHDRAWN

Norton Healthcare

Louisville, Kentucky, 40202, United States

WITHDRAWN

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

COMPLETED

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

COMPLETED

Henry Ford Hospital

Detroit, Michigan, 48202, United States

WITHDRAWN

MD Anderson Cancer Center at Cooper

Camden, New Jersey, 08103, United States

COMPLETED

Columbia University Medical Center

New York, New York, 10032, United States

COMPLETED

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

COMPLETED

OSU Wxner Medical Center

Hilliard, Ohio, 43026, United States

WITHDRAWN

Oregon Health &amp; Science University

Portland, Oregon, 97239, United States

WITHDRAWN

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

WITHDRAWN

Chattanooga's Program in Women's Oncology

Chattanooga, Tennessee, 37403, United States

COMPLETED

Vanderbilt University Medical Center

Nashville, Tennessee, 07677, United States

WITHDRAWN

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

WITHDRAWN

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

COMPLETED

Centre Antoine Lacassagne Centre R gional de Lutte Contre Le Cancer

Nice, Alpes-Maritimes, 06100, France

COMPLETED

ICANS - Institut de canc rologie Strasbourg Europe

Strasbourg, Bas-Rhin, 67200, France

COMPLETED

Institut Paoli Calmettes

Marseille, Bouches-du-Rhone, 13009, France

COMPLETED

Hopitaux de La Timone

Marseille, Bouches-du-Rhone, 13385, France

COMPLETED

Centre Fran ois Baclesse

Caen, Calvados, 1400, France

COMPLETED

Clinique Armoricaine de Radiologie-PPDS

Saint-Brieuc, Cote-d'Amore, 22000, France

WITHDRAWN

EDOG Institut de Cancerologie de l Ouest

Nantes, Loir-Atlantique, 44000, France

COMPLETED

Clinique Catherine de Sienne

Nantes, Loir-Atlantique, 44200, France

WITHDRAWN

Centre Oscar Lambret

Lille, Nord, 59000, France

COMPLETED

Centre Hospitalier de La C te Basque

Bayonne, Pyrenees-Atlantiques, 64109, France

COMPLETED

Centre L on B rard Centre R gional de Lutte Contre Le Cancer Rh ne Alpes

Lyone, Rhone, 69008, France

COMPLETED

CLCC-Gustave Roussy Cancer

Vilejuif, Val-de-Marne, 94805, France

COMPLETED

H pital de la Croix Saint-Simon

Paris, 75020, France

COMPLETED

Hopital Cochin

Paris, 75679, France

COMPLETED

National Cancer Center Hospital

Chuo-ku, Tokyo, 1040045, Japan

RECRUITING

Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 1358550, Japan

RECRUITING

ICO Badalona-H.U. Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital General Universitario Gregorio Mara on

Madrid, 28007, Spain

COMPLETED

Clinica Universidad de Navarra

Madrid, 28027, Spain

COMPLETED

Hospital Clinico San Carlos

Madrid, 28040, Spain

COMPLETED

Hospital Universitario Ramon y Cajal

Madrid, 28304, Spain

COMPLETED

Hospital Universitario de Toledo

Toledo, 45007, Spain

COMPLETED

Fundacion Instituto Valenciano de Oncologia

Valencia, 46009, Spain

COMPLETED

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46013, Spain

COMPLETED

Belfast City Hospital

Belfast, Antrim, BT9 7AB, United Kingdom

WITHDRAWN

Beatson West of Scotland Cancer Centre-PPDS

Glasgow, Glasgow City, G12 0YN, United Kingdom

COMPLETED

The Christie NHS Foundation Trust

Manchester, Lancanshire, M20 4BX, United Kingdom

COMPLETED

Lancashire Clinical Research Facility, Royal Preston Hospital

Preston, Lancanshire, PR2 9HT, United Kingdom

COMPLETED

Guy's and St Thomas's Hospital

London, London, City of, SE1 9RT, United Kingdom

COMPLETED

Mount Vernon Cancer Centre

Northwood, Middlesex, HA6 2RN, United Kingdom

COMPLETED

Velindre Cancer Centre-PPDS

Cardiff, South Glamorgan, CF14 2TL, United Kingdom

COMPLETED

The Royal Marsden in Sutton

Sutton, Surrey, SM2 5PT, United Kingdom

WITHDRAWN

MeSH Terms

Conditions

Neoplasms; Endometrial Neoplasms; Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Ovarian Neoplasms

Interventions

MORAb-202; Prednisone; Prednisolone; Dexamethasone; lenvatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Steroids, Fluorinated

Central Study Contacts

Eisai Medical Information

CONTACT

1-888-274-2378; esi_oncmedinfo@eisai.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The Part A of Dose Optimization is randomized, whereas the Dose Escalation, Dose Confirmation and Part B of Dose Optimization are non-randomized.

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 9, 2020
• Study Start: August 6, 2020
• Primary Completion (Estimated): August 8, 2030
• Study Completion (Estimated): August 8, 2030
• Last Updated: March 13, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

FR (14); US (24); JP (2); GB (8); ES (10)