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

Last updated: December 6, 2024
Sponsor: Eisai Inc.
Overall Status: Active - Recruiting

Phase

1/2

Condition

Neuroblastoma

Treatment

Dexamethasone

Prednisolone

Farletuzumab ecteribulin

Clinical Study ID

NCT04300556
MORAb-202-G000-201
2019-003600-12
2023-506868-14
  • Ages > 18
  • All Genders

Study 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 [EC 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 use of the addition of short course of oral corticosteroids following every dose of farletuzumab ecteribulin (MORAb-202) administered every 21 days, as mitigation strategy for interstitial lung disease (ILD); and to select treatment regimens with farletuzumab ecteribulin (MORAb-202) for further evaluation in Part B. Part B: to further evaluate the safety, tolerability and preliminary efficacy of 2 treatment regimens with farletuzumab ecteribulin (MORAb-202) in participants with advanced EC and to determine the recommended treatment regimen for further development of farletuzumab ecteribulin (MORAb-202).

Eligibility Criteria

Inclusion

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:

  3. TNBC: Histologically confirmed diagnosis of metastatic TNBC (that is, estrogenreceptor (ER) negative/progesterone receptor negative/ human epidermal growthfactor receptor 2 (HER2) negative (defined as immunohistochemistry (IHC) lessthan (<) 2 plus (+) or fluorescence in situ hybridization (FISH) negative)breast cancer). Previously treated with at least one line of systemicanticancer therapy (cytotoxic or targeted anticancer agents) in the metastaticsetting.

  4. NSCLC adenocarcinoma: Histologically or cytologically confirmed metastaticNSCLC adenocarcinoma: participants who have failed previous treatment formetastatic disease, are not indicated or failed epidermal growth factorreceptor (EGFR)-, Anaplastic lymphoma kinase (ALK) -, B-Raf proto-oncogene (BRAF) - or c-ros oncogene 1 (ROS1) - targeted therapy, and for whom noalternative standard therapy exists.

  5. EC: Histologically confirmed diagnosis of advanced, recurrent or metastatic EC.Relapsed or failure of at least one platinum-based regimen or oneimmunotherapy-based regimen.

  6. OC or primary peritoneal cancer or fallopian tube cancer: Histologicallyconfirmed diagnosis of high grade serous epithelial ovarian cancer or primaryperitoneal cancer or fallopian tube cancer. Participants must have:

  • platinum-resistant disease (defined as progression within 6 months after thelast dose of at least 4 cycles of the last platinum containing chemotherapyregimen)

  • received up to 4 lines of systemic therapy post development of platinumresistance. 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. Ovarian cancer or primary peritoneal cancer or fallopian tube cancer:

  • Platinum-resistant disease:

  • For participant with 1 line of platinum-containing therapy: RECIST version 1.1 progression greater than (>) 1 month and less than or equal to (<=) 6months after the last dose of the first platinum-containing chemotherapyregimen (of at least 4 cycles)

  • For participant with 2-3 lines of platinum-containing therapy: RECISTversion 1.1 progression during or within 6 months after the last dose ofthe 2nd or 3rd platinum-containing chemotherapy regimen.

  • Have received up to 3 prior lines of systemic therapy and for whom single-agenttherapy is appropriate as the next line of therapy. Participants may have beentreated with up to one line of therapy subsequent to determination ofplatinum-resistance.

  • Neoadjuvant plus/minus (±) adjuvant will be considered 1 line of therapy.

  • Maintenance therapy (example, bevacizumab, PARP inhibitors) will beconsidered part of the preceding line of therapy (will not be counted asan independent line of therapy).

  • Hormonal therapy will be counted as a separate line of therapy unless itwas given as maintenance.

  • Therapy changed due to toxicity in the absence of progression will beconsidered part of the same line. Endometrial cancer:

  • Participants must have histologically confirmed diagnosis of advanced,recurrent, or metastatic EC. All histologic (including carcinosarcoma [no morethan one participant at any dose level]) and molecular subtypes will beincluded. Participants may have been treated with an Immune CheckpointInhibitor (ICI) containing regimen (or be ineligible for ICI treatment) andmust have had no more than 2 prior regimens (not including adjuvant therapy ifprogression or recurrent/metastatic disease occurred more than 6 months afterthe completion of the last cycle of adjuvant therapy).

  • Note: There is no restriction regarding prior hormonal therapy.

  1. Available tumor tissue for FRA expression percent (%) by IHC analysis as assessed ata central laboratory. There is no minimum requirement for FRA expression (%).However, the tumor sample must be evaluable for IHC analysis (that is, of sufficientquality with adequate tumor content). Sample resubmission will be permitted forparticipants with tissue result of "non-evaluable" who are otherwise eligible. Tumorsample submission must be archival formalinfixed, paraffin-embedded (FFPE) tissueblock, or unstained slides sectioned within 45 days from the latest FFPE block, or afresh biopsy sample obtained during screening but prior to initiation of studytreatment.

  2. Radiological disease progression on or after the most recent therapy by investigatorassessment.

  3. Measurable disease meeting the following criteria (confirmed by central radiographicreview, in the Dose-Confirmation Part and in Dose Optimization Part B only):

  • At least one lesion of >1.0 centimeter (cm) in long axis diameter for non-lymphnodes or >1.5 cm in short axis diameter for lymph nodes that is seriallymeasurable according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using either computed tomography (CT) or magnetic resonance imaging (MRI),

  • Lesions that have had external beam radiotherapy (EBRT) or loco-regionaltherapies such as radiofrequency (RF) ablation must show evidence of PD basedon RECIST 1.1 to be deemed a target lesion.

  1. ECOG PS of 0 or 1.

  2. Participants who are expected to survive a minimum of 3 months after the firstadministration of the study drug.

  3. Adequate renal function as evidenced by serum creatinine less than or equal to (<=) 1.5 milligram per deciliter (mg/dL) or calculated creatinine clearance >=50milliliter per (mL) /minute according to a 12 or 24 hour urine collection.

  4. Adequate bone marrow function, as evidenced by:

  • Absolute neutrophil count (ANC) >=1.0*10^9 per liter (/L)

  • Hemoglobin (Hgb) >=9.0 gram per deciliter (g/dL)

  • Platelet count >=75*10^9/L Growth factors or transfusions as per institutionalpractice, are allowed if needed to achieve the above values. Growth factor andplatelet transfusion should not be used within 7 days of initiation of studytreatment.

  1. Adequate liver function, as evidenced by:
  • Total bilirubin <=1.5*upper limit of normal (ULN) except for unconjugatedhyperbilirubinemia (example, Gilbert's syndrome)

  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3ULN (inthe case of liver metastases <=5ULN). Participants with Alkaline Phosphatase (ALP) <=3*ULN unless they and are known to have bone metastases in which casehigher ALP values will also be allowed.

  • Albumin >3.0 g/dL.

  1. Participants must undergo a washout period required from the end of prior treatmentto the first administration of the study drug that will be as follows: Prior anticancer therapy:
  • Prior chemotherapy, surgical therapy, radiation therapy: >3 weeks. Prior chestradiotherapy or pneumonectomy is an exclusion.

  • Antibody and other biologic therapeutic agents: >=4 weeks.

  • Endocrine therapy or, small-molecule targeted therapy: >2 weeks.

  • Immunotherapy >=4 weeks.

  1. Participants with a history of deep vein thrombosis (DVT) within 3 months ofenrollment must be on a stable dose of anticoagulation as demonstrated byappropriate laboratory parameters (depending on the anticoagulant agent) for aminimum of 2 weeks prior to starting study treatment. Anticoagulation must continuewhile on study treatment.

  2. Participants at risk for DVT secondary to central venous catheters or with pastmedical history of DVT or clinical symptoms suggestive of DVT must have venousDoppler ultrasonography to rule out DVT during the screening period and prior toinitiation of study treatment.

  3. If a participant has undergone major surgery, the participant must have recoveredadequately from the toxicity and/or complications from the intervention prior tostarting study treatment.

  4. Resolution of anticancer therapy-related or radiation-related toxicities to Grade 1severity or lower, except for stable sensory neuropathy (Grade <=2), anemia ([haemoglobin] Hgb >=9.0 g/dL), and alopecia (any grade).

  5. Participant must be willing and able to comply with all aspects of the protocol.

  6. Participant must provide written informed consent prior to any study-specificscreening procedures.

Exclusion

Exclusion Criteria:

  1. Participants with endometrial leiomyosarcoma, endometrial stromal sarcoma or othersoft tissue sarcoma histology.

  2. Participants who received previous treatment with any folate receptor targetingagents.

  3. Participants with platinum refractory ovarian cancer (defined as disease progressionduring the initial platinum-based chemotherapy treatment).

  4. Currently enrolled in another clinical study or used any investigational drug ordevice, 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 fallsunder the parameters these Inclusion Criteria should be followed) of anyinvestigational drug preceding informed consent.

  5. Participants with brain or subdural metastases are not eligible, unless they havecompleted local therapy and have discontinued the use of corticosteroids for thisindication for at least 2 weeks before starting treatment in this study. Brainmetastases must be stable for at least 4 weeks on 2 consecutive scans of the brainbefore starting study treatment.

  6. Diagnosed with meningeal carcinomatosis.

  7. Any other invasive malignancy that required treatment (other than definitivesurgery) or has shown evidence of recurrence/progression (except for non-melanomaskin cancer, or histologically confirmed complete excision of carcinoma in situ)during the 2 years prior to starting study treatment.

  8. Significant cardiovascular impairment. History within 6 months prior to the firstdose of study drug of: congestive heart failure greater than New York HeartAssociation (NYHA) Class II); unstable angina; myocardial infarction; stroke;cardiac arrhythmia associated with hemodynamic instability.

  9. Clinically significant ECG abnormality, including marked prolonged baseline QT ascorrected using Fridericia's formula (QTcF) (repeated demonstration of a QTcFinterval >500 milliseconds [ms]). A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the useof concomitant medications that prolong the QTcF.

  10. Known to be Human Immunodeficiency Virus (HIV) positive. Testing at entry notrequired.

  11. Active viral hepatitis (B or C as demonstrated by positive serology). Testing atentry if there are no symptoms or history is not required unless as per localrequirements.

  12. Females who are breastfeeding or pregnant at Screening or Baseline (as documented bya positive beta human chorionic gonadotropin [ß-hCG] or human chorionic gonadotropin [hCG]) with a minimum sensitivity of 25 International units per liter (IU/L) orequivalent units of ß-hCG [or hCG]. A separate baseline assessment is required if anegative screening pregnancy test was obtained more than 72 hours before the firstadministration of the study drug.

  13. Females of childbearing potential who

  • within 28 days before study entry, did not use a highly effective method ofcontraception, which includes any of the following:

  • total abstinence (if it is their preferred and usual lifestyle)*

  • an intrauterine device or intrauterine hormone-releasing system (IUS)

  • a contraceptive implant

  • combined (estrogen and progestogen containing) hormonal contraceptionassociated with inhibition of ovulation (oral, intravaginal, transdermal)or progestogen-only hormonal contraception associated with inhibition ofovulation (oral, injectable, implantable). Participants using an oralcontraceptive (participant must be on a stable dose of the same oralcontraceptive product for at least 28 days before dosing and throughoutthe study and for 7 months (5*half-life plus 180 days) after study drugdiscontinuation)

  • bilateral tubal occlusion

  • have a vasectomized partner with confirmed azoospermia

  • do not agree to use a highly effective method of contraception (as describedabove) 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 ofcontraception is not appropriate or acceptable to the participant, then theparticipant must agree to use a medically acceptable method of contraception, thatis, double-barrier methods of contraception such as latex or synthetic condom plusdiaphragm or cervical/vault cap with spermicide. NOTE: All females will beconsidered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, andwithout other known or suspected cause) or have been sterilized surgically (that is,bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all withsurgery at least 1 month before dosing).

*Sexual abstinence is considered a highly effective method only if defined asrefraining from heterosexual intercourse during the entire period of risk associatedwith the study intervention. The reliability of sexual abstinence needs to beevaluated in relation to the duration of the study and the preferred and usuallifestyle of the participant.

  1. For Dose-Escalation only: Males who have not had a successful vasectomy (confirmedazoospermia) or they and their female partners do not meet the criteria above (thatis, not of childbearing potential or practicing highly effective contraceptionthroughout the study period and for 7 months (5half-life plus 180 days) after studydrug discontinuation). If the female partner is pregnant, then males who do notagree to use latex or synthetic condoms throughout the study period and for 4 months (5half-life plus 90 days) after study drug discontinuation. No sperm donation isallowed during the study period and for 4 months (5*half-life plus 90 days) afterstudy drug discontinuation.

  2. Pulmonary Function Test (PFT) abnormalities: FEV1/FVC <0.7, FEV1 or FVC <80%, DLCO <80% or less than the lower limit of normal according to local institutionalstandards.

  3. Current ILD/pneumonitis, or ILD/pneumonitis is suspected at Screening or history ofinterstitial lung disease (ILD)/pneumonitis of any severity includingILD/pneumonitis from prior anticancer therapy.

  4. Current infectious pneumonia, history of viral pneumonia (including COVID-19-relatedinfection) with evidence of persistent radiologic abnormalities.

  5. Lung-specific clinically significant illnesses including, but not limited to anyunderlying pulmonary disorder (example, pulmonary embolism), asthma, chronicobstructive pulmonary disease (COPD), and restrictive lung disease, or currentlyreceiving any medication that is associated with a clinically significant risk ofdeveloping ILD.

  6. Clinically significant pleural or pericardial effusion requiring drainage or ascitesrequiring peritoneal shunt.

  7. Prior pneumonectomy.

  8. History of chest radiotherapy. Participants with history of chest wall radiation (example, history of breast cancer) may be permitted if chest wall radiation isdocumented > 2 years before starting study treatment.

  9. Any autoimmune, connective tissue, or inflammatory disorders (example, rheumatoidarthritis, Sjögren's syndrome, sarcoidosis, etc) where there is documented (orsuspicion of) pulmonary involvement.

  10. A known history of active TB (bacillus tuberculosis).

  11. Scheduled for surgery during the study, other than minor surgery which would notdelay study treatment.

  12. An active clinically significant (in the opinion of the Investigator) infectionrequiring systemic therapy within 2 weeks prior to the first dose of study drug.

  13. Administration of a live, attenuated vaccine within 4 weeks prior to the first doseof study drug, or anticipation that such a live attenuated vaccine will be requiredduring the study. Inactivated vaccines (such as hepatitis A or polio vaccines) arepermitted during the study. Seasonal influenza and COVID-19 vaccines that do notcontain live virus are permitted.

  14. Any prior hypersensitivity to monoclonal antibodies or contraindication to thereceipt of corticosteroids or any of the excipients (investigators should refer tothe prescribing information for the selected corticosteroid).

  15. Known intolerance to either of the components of the study drug.

  16. Any medical or other condition which, in the opinion of the investigator wouldpreclude the participants participation in the clinical study.

  17. Receiving any medication prohibited in combination with the study treatment(s) asdescribed in the product label for eribulin, unless medication was stopped within 7days prior to enrollment.

  18. Known psychiatric or substance abuse disorders that would interfere with cooperationwith the requirements of the trial.

Study Design

Total Participants: 142
Treatment Group(s): 4
Primary Treatment: Dexamethasone
Phase: 1/2
Study Start date:
August 06, 2020
Estimated Completion Date:
December 31, 2024

Connect with a study center

  • Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer

    Nice, Alpes-Maritimes 6100
    France

    Active - Recruiting

  • ICANS - Institut de cancérologie Strasbourg Europe

    Strasbourg, Bas-Rhin 67200
    France

    Active - Recruiting

  • Institut Paoli Calmettes

    Marseille, Bouches-du-Rhone 13009
    France

    Site Not Available

  • Hopitaux de La Timone

    Marseille, Bouches-du-Rhône 13385
    France

    Site Not Available

  • Centre François Baclesse

    Caen, Calvados 14000
    France

    Site Not Available

  • Clinique Amoricaine de Radiologie

    Saint-Brieuc, Cote-d'Amore 22000
    France

    Site Not Available

  • Clinique Catherine de Sienne

    Nante, Loire-Atlantique 44200
    France

    Site Not Available

  • Clinique Catherine de Sienne

    Nantes, Loire-Atlantique 44200
    France

    Site Not Available

  • EDOG Institut de Cancerologie de l'Ouest - PPDS

    Nantes, Loire-Atlantique 44000
    France

    Active - Recruiting

  • Centre Oscar Lambret

    Lille, Nord 59000
    France

    Site Not Available

  • Centre Hospitalier de la Cote Basque

    Bayonne, Pyrenees-Atlantiques 64109
    France

    Site Not Available

  • Centre Leon Berard Centre Regional de Lutte Contre

    Lyon, Rhone 69008
    France

    Active - Recruiting

  • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes

    Lyon, Rhône 69008
    France

    Active - Recruiting

  • CLCC - Gustave Roussy Cancer

    Villejuif, Val-de-Marne 94805
    France

    Active - Recruiting

  • Hopital Cochin

    Paris, 75679
    France

    Site Not Available

  • Hôpital de la Croix Saint-Simon

    Paris, 75020
    France

    Site Not Available

  • ICO Badalona-H.U. Germans Trias i Pujol

    Badalona, Barcelona 8916
    Spain

    Active - Recruiting

  • Hospital Universitario Vall d'Hebron - PPDS

    Barcelona, 8035
    Spain

    Active - Recruiting

  • Clinica Universidad Navarra - Madrid

    Madrid, 28027
    Spain

    Site Not Available

  • Hospital Clinico San Carlos

    Madrid, 28040
    Spain

    Active - Recruiting

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007
    Spain

    Site Not Available

  • Hospital Universitario Ramon y Cajal

    Madrid, 28304
    Spain

    Active - Recruiting

  • Hospital Universitario de Toledo

    Toledo, 45007
    Spain

    Site Not Available

  • Fundacion Instituto Valenciano de Oncologia

    Valencia, 46009
    Spain

    Active - Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010
    Spain

    Active - Recruiting

  • Hospital Universitari i Politecnic La Fe de Valencia

    Valencia, 46013
    Spain

    Active - Recruiting

  • Belfasr City Hospital

    Belfast, Antrim BT9 7AB
    United Kingdom

    Site Not Available

  • Lancashire Clinical Research Facility, Royal Preston Hospital

    Preston, Lancashire PR2 9HT
    United Kingdom

    Active - Recruiting

  • Mount Vernon Cancer Centre

    Northwood, Middlesex HA6 2RN
    United Kingdom

    Site Not Available

  • Velindre Cancer Centre - PPDS

    Cardiff, South Glamorgan CF14 2TL
    United Kingdom

    Active - Recruiting

  • The Royal Marsden

    Sutton, Surrey SM2 5PT
    United Kingdom

    Site Not Available

  • Beatson West of Scotland Cancer Centre - PPDS

    Glasgow, G12 0YN
    United Kingdom

    Active - Recruiting

  • Guys and St Thomas's Hospital

    London, SE1 9RT
    United Kingdom

    Active - Recruiting

  • The Christie NHS Foundation Trust - PPDS

    Manchester, M20 4BX
    United Kingdom

    Active - Recruiting

  • Arizona Clinical Research Center - Hunt - PPDS

    Tucson, Arizona 85715
    United States

    Site Not Available

  • University of Arkansas For Medical Sciences

    Little Rock, Arkansas 72205
    United States

    Site Not Available

  • Stanford University School of Medicine

    Stanford, California 94305
    United States

    Active - Recruiting

  • H Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida 33612
    United States

    Active - Recruiting

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • Georgia Cancer Center at Augusta University

    Augusta, Georgia 30912
    United States

    Active - Recruiting

  • Northwestern University

    Chicago, Illinois 60611
    United States

    Active - Recruiting

  • Orchard Healthcare Research Inc

    Skokie, Illinois 60077
    United States

    Site Not Available

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland 21231
    United States

    Active - Recruiting

  • Henry Ford Health System

    Detroit, Michigan 48202
    United States

    Site Not Available

  • Memorial Sloan Kettering Cancer Center

    Detroit, Michigan 48201-2013
    United States

    Site Not Available

  • MD Anderson Cancer Center at Cooper

    Camden, New Jersey 08103
    United States

    Completed

  • Barbara Ann Karmanos Cancer Institute

    New Brunswick, New Jersey 08901-1914
    United States

    Site Not Available

  • MD Anderson Cancer Center at Cooper

    Voorhees, New Jersey 08043
    United States

    Site Not Available

  • Columbia University Medical Center

    New York, New York 10032
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York 11065
    United States

    Active - Recruiting

  • University of Cincinnati Medical Center

    Cincinnati, Ohio 45219
    United States

    Active - Recruiting

  • Ohio State University

    Columbus, Ohio 43210
    United States

    Completed

  • Oregon Health and Science University

    Portland, Oregon 97239
    United States

    Site Not Available

  • Chattanooga's Program In Women's Oncology

    Chattanooga, Tennessee 37403
    United States

    Completed

  • University of Texas MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Site Not Available

  • University of Texas MD Anderson Cancer Centre

    Houston, Texas 77030
    United States

    Site Not Available

  • University of Virginia Health System

    Charlottesville, Virginia 22908
    United States

    Completed

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