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

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ClinicalTrials.gov Identifier: NCT04300556
Recruitment Status : Recruiting
First Posted : March 9, 2020
Last Update Posted : March 29, 2021
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
The primary objectives of the study are: (1) in the dose-escalation part: to evaluate safety, tolerability and to determine the recommended Phase 2 dose (RP2D) of MORAb-202, and (2) in an expansion part: to evaluate the objective response rate (ORR) in each of the selected tumor types at the RP2D.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: MORAb-202 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 196 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label Phase 1/2 Trial Evaluating the Safety, Tolerability, and Efficacy of MORAb-202, a Folate Receptor Alpha (FRα)-Targeting Antibody-drug Conjugate (ADC) in Subjects With Selected Tumor Types
Actual Study Start Date : August 6, 2020
Estimated Primary Completion Date : August 28, 2022
Estimated Study Completion Date : August 28, 2025

Arm Intervention/treatment
Experimental: MORAb-202

Dose Escalation: Participants will receive MORAb-202 at a starting dose of 0.9, 1.2, 1.6 milligram per kilogram (mg/kg) administered as an intravenous infusion once every 3 weeks in a 21 days cycle.

Expansion: Participants will receive MORAb-202 at a recommended Phase 2 dose (RP2D) determined in dose escalation part, administered as an intravenous infusion once every 3 weeks in a 21 days cycle.

Drug: MORAb-202
MORAb-202 intravenous infusion.




Primary Outcome Measures :
  1. Dose Escalation Part: Recommended Phase 2 Dose (RP2D) of MORAb-202 [ Time Frame: Cycle 1 (Cycle length is equal to [=] 21 days) ]
  2. Dose Expansion Part: Objective Response Rate (ORR) [ Time Frame: From date of first dose of study drug until first documentation of CR or PR (up to approximately 2 years) ]
    ORR was 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.

  3. Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Cycle length = 21 days) ]
    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).

  4. Number of Participants with Adverse Events (AEs) and Adverse Events of Interest (AEIs) [ Time Frame: Baseline up to 28 days after the last dose of study drug (approximately 2 years) ]
    AEIs are AEs that may be associated with the use of immunomodulatory drugs, such as infections, malignancies, autoimmune disorders, and injection reactions.

  5. Number of participants with Clinically Significant Change From Baseline in Clinical Laboratory Values, Vital Signs, Body Weight and 12-lead Electrocardiograms [ Time Frame: Baseline up to 28 days after the last dose of study drug (approximately 2 years) ]
  6. Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG) Performance Status [ Time Frame: Baseline, up to approximately 2 years ]
  7. Number of Participants with Serum Anti-Drug Antibodies (ADA) Titer to MORAb-202 [ Time Frame: Cycles (1-6) Day 1: pre-infusion and off treatment visit, within 28 days of last dose of study drug (approximately 2 years) (Cycle length=21 days) ]

Secondary Outcome Measures :
  1. Duration of Response (DOR) [ Time Frame: From first documented CR or PR until first documentation of recurrent or progressive disease or death (approximately 5 years) ]
    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.

  2. Disease Control Rate (DCR) [ Time Frame: From first dose of study drug until first documentation of CR or PR or SD (approximately 5 years) ]
    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.

  3. Clinical Benefit Rate (CBR) [ Time Frame: From first dose of study drug until disease progression or death, whichever occurs first (approximately 5 years) ]
    CBR is defined as the percentage of participants with BOR of CR, PR, or durable SD (duration of SD greater than or equal to [>=] 23 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.

  4. Progression Free Survival (PFS) [ Time Frame: From first dose of study drug until disease progression, death, whichever occurs first (approximately 5 years) ]
    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.

  5. Overall Survival (OS) [ Time Frame: From first dose of study drug until death (approximately 5 years) ]
    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.

  6. Pharmacokinetics (PK) Profiles of MORAb-202 [ Time Frame: Cycles (1-6) Day 1: pre-infusion to 336 hours post-infusion, (Cycle length=21 days) ]
  7. Total Antibody Concentration for Eribulin and MORAb-202 [ Time Frame: Cycles (1-6) Day 1: pre-infusion up to 336 hours post-infusion and off treatment visit (within 28 days of last dose of study drug) (Cycle length=21 days) ]
  8. Relationship Between Folate Receptor Alpha (FRA) Expression Levels and Clinical Outcome [ Time Frame: Baseline up to 28 days after the last dose of study drug (approximately 1 year 7 months) ]
    Evaluate how clinical outcomes like objective response and progression free survival correlate with the level of expression of FRA in tumors.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged >=18 years
  2. Females (Triple-negative breast cancer [TNBC], endometrial and ovarian cancer) or males/females (NSCLC, adenocarcinoma). Participants with the following disease characteristics:

    Participants with the following tumor types, each as a separate arm:

    1. 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.
    2. 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.
    3. Endometrial cancer (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.
    4. Ovarian cancer 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.
  3. FRA-positive tumors (in the Expansion Part only). FRA expression to be assessed by immunohistochemistry (IHC) at a central laboratory using formalin-fixed, paraffin-embedded (FFPE) tissue samples. FRA positivity is defined as membrane staining in >=5% of neoplastic cells at any intensity level.
  4. Available tumor tissue for FRA expression analysis. Either archival paraffin-embedded formalin-fixed (FFPE) tissue or newly obtained biopsies are acceptable if obtained under standard of care.
  5. Radiological disease progression on or after the most recent therapy by investigator assessment.
  6. Measureable disease meeting the following criteria (confirmed by central radiographic review, in the Expansion Part only):

    • At least one lesion of greater than (>) 1.0 centimeter (cm) in long axis diameter for non-lymph nodes or >1.5 cm in short axis diameter for lymph nodes that is serially measurable 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-regional therapies such as radiofrequency (RF) ablation must show evidence of PD based on RECIST 1.1 to be deemed a target lesion.
  7. ECOG PS of 0 or 1.
  8. Participants who are expected to survive a minimum of 3 months after the first administration of the study drug.
  9. Adequate renal function as evidenced by serum creatinine less than or equal to (<=) 1.5 milligram per deciliter (mg/dL) or calculated creatinine clearance >=50 milliliter per (mL) /minute according to a 12 or 24 hour urine collection.
  10. Adequate bone marrow function, as evidenced by:

    • 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 are allowed (up to 2 weeks before study entry) if needed to achieve the above values.
  11. Adequate liver function, as evidenced by:

    • Total bilirubin <=1.5*upper limit of normal (ULN) except for unconjugated hyperbilirubinemia (example, Gilbert's syndrome)
    • Alkaline phosphatase (ALP), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3*ULN (in the case of liver metastases <=5*ULN). In case ALP is >3*ULN (in absence of liver metastases) or >5*ULN (in presence of liver metastases) AND participant also is known to have bone metastases, the liver specific ALP isoenzyme must be separated from the total and used to assess the liver function instead of the total ALP.
    • Albumin >3.0 g/dL.
  12. Participants must undergo a washout period required from the end of prior treatment to the first administration of the study drug that will be as follows:

    Prior anticancer therapy:

    • Prior chemotherapy, surgical therapy, radiation therapy: >3 weeks.
    • Antibody and other biologic therapeutic agents: >=4 weeks.
    • Endocrine therapy or, small-molecule targeted therapy: >2 weeks.
    • Immunotherapy >=4 weeks.

    Supportive therapies:

    • Blood/platelet transfusion, hematopoietic stimulating agent including granulocyte colony-stimulating factor (G-CSF) formulation: >=2 weeks.

  13. If a participant has undergone major surgery, the participant must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
  14. Resolution of anticancer therapy-related or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy (Grade <=2), anemia ([haemoglobin] Hgb >=9.0 g/dL), and alopecia (any grade).
  15. Participant must be willing and able to comply with all aspects of the protocol.
  16. Participant must provide written informed consent prior to any study-specific screening Procedures.

Exclusion Criteria:

  1. Participants who received previous treatment with any folate receptor targeting agents.
  2. Participants with platinum refractory ovarian cancer (defined as disease progression during the initial platinum-based chemotherapy treatment).
  3. 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.
  4. 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 4 weeks before starting treatment in this study. Any signs (example, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
  5. Diagnosed with meningeal carcinomatosis.
  6. Any other 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.
  7. 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.
  8. Clinically significant ECG abnormality, including marked prolonged baseline QT as corrected using Fridericia's formula (QTcF) (repeated demonstration of a QTcF interval >500 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.
  9. Previously known to be Human Immunodeficiency Virus (HIV) positive. Testing at entry not required.
  10. Active viral hepatitis (B or C as demonstrated by positive serology).
  11. 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 litre (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. Scheduled for surgery during the study, other than minor surgery which would not delay study treatment.
  12. 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 intrauterine hormone-releasing system (IUS)
    • a contraceptive implant
    • 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 90 days after study drug discontinuation)
    • have a vasectomized partner with confirmed azoospermia
    • do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 90 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 participant, then the participant must agree to use a medically acceptable method of contraception, that is, double-barrier methods of contraception such as latex or synthetic condom plus diaphragm or cervical/vault cap with spermicide. NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).

    *Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study intervention. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.

  13. Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period and for 90 days after study drug discontinuation). If the female partner is pregnant, then males who do not agree to use latex or synthetic condoms throughout the study period and for 90 days after study drug discontinuation. No sperm donation is allowed during the study period and for 90 days after study drug discontinuation.
  14. Any history of non-infectious pneumonitis or current pneumonitis.
  15. Currently has active, or a history of, interstitial lung disease (ILD).
  16. Has a known history of active TB (bacillus tuberculosis).
  17. Scheduled for surgery during the study, other than minor surgery which would not delay study treatment.
  18. Has an active infection requiring systemic therapy within 4 weeks prior to the first dose of study drug.
  19. Administration of a live, attenuated vaccine within 4 weeks prior to the first dose of study drug, or anticipation that such a live attenuated vaccine will be required during the study. Inactivated vaccines (such as hepatitis A or polio vaccines) are permitted during the study. Seasonal influenza vaccines that do not contain live virus are permitted.
  20. Known intolerance to either of the components of the study drug.
  21. Any medical or other condition which, in the opinion of the investigator would preclude the participants participation in the clinical study.
  22. Is receiving any medication prohibited in combination with the study treatment(s) as described in the product label for eribulin, unless medication was stopped within 7 days prior to enrollment.
  23. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04300556


Contacts
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Contact: Eisai Medical Information 1-888-274-2378 esi_oncmedinfo@eisai.com

Locations
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United States, Florida
H Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Georgia Cancer Center at Augusta University Recruiting
Augusta, Georgia, United States, 30912
United States, Illinois
Orchard Healthcare Research Inc Active, not recruiting
Skokie, Illinois, United States, 60077
United States, Michigan
Henry Ford Health System Active, not recruiting
Detroit, Michigan, United States, 48202
United States, New Jersey
MD Anderson Cancer Center at Cooper Recruiting
Voorhees, New Jersey, United States, 08043
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
United States, Ohio
University of Cincinnati Medical Center Active, not recruiting
Cincinnati, Ohio, United States, 45267
United States, Oregon
Oregon Health and Science University Active, not recruiting
Portland, Oregon, United States, 97239
United States, Tennessee
Chattanooga's Program In Women's Oncology Active, not recruiting
Chattanooga, Tennessee, United States, 37403
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22903
Sponsors and Collaborators
Eisai Inc.
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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT04300556    
Other Study ID Numbers: MORAb-202-G000-201
2019-003600-12 ( EudraCT Number )
First Posted: March 9, 2020    Key Record Dates
Last Update Posted: March 29, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eisai Inc.:
MORAb-202
Neoplasms
Endometrial Neoplasms
Negative Breast Cancer
Endometrial Carcinoma
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Folate Receptor Alpha (FRA)