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A Study of MORAb-202 in Participants With Solid Tumors

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ClinicalTrials.gov Identifier: NCT03386942
Recruitment Status : Recruiting
First Posted : December 29, 2017
Last Update Posted : May 28, 2018
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
The primary objective of this study is to evaluate the tolerability and safety profile of MORAb-202 in participants with solid tumors.

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This is a Phase 1 study of MORAb-202 in participants with solid tumors. This study will be conducted in 2 parts (Part 1 and Part 2). Part 1 will be the dose escalation portion of this study to evaluate dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) of MORAb-202 in participants with solid tumors. Considering efficacy, safety, and the pharmacokinetic (PK) profile, one dose may be selected from Part 1 for Part 2. Part 2 will comprise cohort expansions to further characterize the safety of MORAb-202 and to evaluate the preliminary efficacy of MORAb-202 in participants with folate receptor α (FRA)-positive triple negative breast cancer (TNBC) and Type 2 endometrial carcinoma. The recommended dose for future studies will be determined based on the data from Part 1 and Part 2.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of MORAb-202 in Subjects With Solid Tumors
Actual Study Start Date : November 28, 2017
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Arm Intervention/treatment
Experimental: MORAb-202

Part 1 (Dose-escalation): The initial dose level of MORAb-202 will be 0.3 milligrams per kilogram (mg/kg) every 3 weeks in the first cohort with 1 participant for dose-limiting toxicity (DLT) evaluation. DLTs will be evaluated in successive dose level cohorts with a single participant until a drug-related Grade 2 or higher toxicity is observed. If such a toxicity is observed, the cohort will be expanded to enroll a total of 3 participants.

Part 2 (Treatment Phase): MORAb-202 will be administered every 3 weeks during the treatment phase at the dose determined in Part 1 until participants meet any of the criteria for discontinuation. Criteria for discontinuation include: withdrawal of consent, major protocol violations, unable to continue due to adverse events, pregnancy, progressive disease, Investigator decision, or infusion reactions.

Drug: MORAb-202
Part 1: MORAB-202 intravenous (IV) infusion administered every 3 weeks. starting at a 0.3 mg/kg dose and successively increasing doses until DLT. Part 2: MORAb-202 administered IV every 3 weeks at a dose determined in Part 1 until any of the criteria for discontinuation are met.




Primary Outcome Measures :
  1. Part 1: Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: At the end of Cycle 1 (21 days) ]
    The following toxicities developed in Cycle 1 and causal relationship with MORAb-202 cannot be ruled out are regarded as DLTs: 1) febrile neutropenia; 2) Grade 4 neutropenia that persists for more than 7 days or that requires hematopoietic-stimulating agents; 3) Grade 4 thrombocytopenia, or thrombocytopenia that requires platelet transfusion; 4) Grade 4 anemia or anemia that requires blood transfusion; 5) any Grade 3 non-hematological toxicity with the exception of: a) abnormal clinical laboratory values with no clinical significance; b) any events that can be managed and controlled to Grade 2 or less by maximal medical management; c) infusion reactions of Grade 3 or higher are not considered DLTs because they are stochastic and idiosyncratic events, not related to dose; 6) any Grade 4 non-hematologic toxicity; 7) development of any toxicity that is considered to be related to MORAb-202 and where dose at C2D1 is necessary to postpone for over 14 days for recovery from the toxicities.

  2. Part 1 and Part 2: Number of participants with adverse events (AEs), adverse events of interest (AEIs), and serious adverse events (SAEs) [ Time Frame: Up to 22 months ]
  3. Number of participants with any clinically significant clinical laboratory test value [ Time Frame: Up to 22 months ]
    Clinical significance will be determined by the Investigator.

  4. Number of participants with any clinically significant vital sign value [ Time Frame: Up to 22 months ]
    Clinical significance will be determined by the Investigator.

  5. Change from Baseline in arterial oxygen saturation [ Time Frame: Baseline; up to 22 months ]
  6. Change from Baseline in body weight [ Time Frame: Baseline; up to 22 months ]
  7. Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value [ Time Frame: Up to 22 months ]
    Clinical significance will be determined by the Investigator.

  8. Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG) [ Time Frame: Baseline; up to 22 months ]
  9. Change from Baseline in serum anti-drug antibody (ADA) titer [ Time Frame: Baseline; up to 22 months ]

Secondary Outcome Measures :
  1. Part 1: Maximum Tolerated Dose (MTD) of MORAb-202 [ Time Frame: 21 days following each dose level of MORAb-202 (up to a maximum of 22 months) ]
    The MTD will be selected as the dose with the smallest difference between the target DLT rate of 25% and an estimate of DLT rate based on the posterior distribution of DLT rate for each dose.

  2. Part 1 and Part 2: Maximum observed serum concentration (Cmax) of MORAb-202 [ Time Frame: Predose; end of infusion; 0.5, 1, 2, 4, and 24 hours (h) post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 22 months) ]
    Cmax is the maximum serum concentration of MORAb-202 after administration of the drug.

  3. Part 1 and Part 2: Maximum serum concentration of total antibody [ Time Frame: Predose; end of infusion; 0.5, 1, 2, 4, and 24 h post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 22 months) ]
  4. Part 1 and Part 2: Plasma concentration of free eribulin [ Time Frame: Predose; end of infusion; 0.5, 1, 2, 4, 24 h post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 22 months) ]
  5. Recommended dose (RD) of MORAb-202 for future studies [ Time Frame: From the date of screening until the last observation visit (up to 22 months) ]
    The RD will be determined based on the MTD, efficacy, and safety data in Part 1 and Part 2

  6. Part 1 and Part 2: Best overall response (BOR) [ Time Frame: From the date of screening until the last observation visit (up to 22 months) ]
    BOR was based on Response Evaualtion Criteria in Solid Tumors version 1.1 (RECIST v1.1). BORs are complete response (CR), partial response (PR), stable disease (SD), progression of disease (PD), and not evaluable (NE), where SD has to be achieved at ≥5 weeks after the first dose. CR or PR in Part 1 of this study requires no confirmation of the next response at ≥4 weeks. CR or PR in Part 2 of this study requires confirmation of the next response at ≥4 weeks.

  7. Part 1 and Part 2: Overall response rate (ORR) [ Time Frame: From the date of screening until the last observation visit (up to 22 months) ]
    ORR is defined as the percentage of participants with BOR of CR or PR.

  8. Part 1 and Part 2: Disease control rate (DCR) [ Time Frame: From the date of screening until the last observation visit (up to 22 months) ]
    DCR is defined as the percentage of participants with BOR of CR, PR, or SD.

  9. Part 1 and Part 2: Clinical benefit rate (CBR) [ Time Frame: From the date of screening until the last observation visit (up to 22 months) ]
    CBR is defined as the percentage of participants with BOR of CR, PR or durable (SD) (duration of SD ≥ 23 weeks).

  10. Part 2: Progression-free survival (PFS) [ Time Frame: From the date of screening until disease progression or death (up to 22 months) ]
    PFS is defined as the time from the date of the first dose of study drug to the first documented date of event (disease progression or death from any cause, whichever occurs first).

  11. Part 2: Overall Survival (OS) [ Time Frame: From the date of screening until the last observation visit (up to 22 months) ]
    OS is defined as the time from the date of the first dose to the date of death from any cause. For participants who are alive or unknown, OS is censored as the date of the last known alive date or the date of data cut off, whichever comes first.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants who have provided voluntary written consent for participation in this clinical study.
  • Participants to whom the rules for complying with this clinical study have been adequately explained, and who intend to and can comply with those rules.
  • Male or female participants age ≥ 20 years at the time of informed consent of screening 1 (at screening 2, in case of participants who enter this clinical study from screening 2).
  • Participants with folate receptor α (FRA)-positive solid tumor confirmed by immunohistochemistry (IHC) at central laboratory using their available tumor samples from resected specimen (i.e., surgical or excisional/incisional biopsy samples)
  • At informed consent of screening 2, participants who failed standard therapies, or for which no appropriate treatment is available.
  • Participants with adequate function of major organs within 2 weeks prior to the first administration of the study drug as follows.

    1. Hemoglobin ≥ 9.0 grams per deciliter (g/dL).
    2. Neutrophil count ≥ 1.5 × 10^3/microliters (μL).
    3. Platelet count ≥ 10 × 10^4/μL.
    4. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) in the facility.
    5. Alanine aminotransferase and aspartate aminotransferase ≤ 3.0 × ULN in the facility.
    6. Serum creatinine ≤ 1.5 × ULN in the facility.
    7. Albumin ≥ 3 g/dL.
  • Participants with Performance Status score of 0-1 established by Eastern Cooperative Oncology Group.
  • Participants who are expected to survive for 3 months or longer after the first administration of the study drug.
  • Washout period required from the end of prior treatment to the first administration of the study drug will be as follows

    1. Anticancer therapy

      • Antibody and other study drugs: > 4 weeks (however, in the case where the half-life of other study drugs is known and 5 × half-lives of that study drug is less than or equal to 4 weeks, participants can be eligible after ≥ 5 × half-lives of that study drug has passed).
      • Prior chemotherapy (except small-molecule targeted therapy), surgical therapy, radiation therapy: >3 weeks.
      • Endocrine therapy, immunotherapy except antibody, small-molecule targeted therapy: >2 weeks.
    2. Supportive therapies • Blood/platelet transfusion, hematopoietic stimulating agent including granulocyte colony-stimulating factor formulation: > 2 weeks.
  • Participants whose formalin fixed, paraffin-embedded unstained slides of tumor sample must be available for IHC test at central laboratory. Biopsy should be excisional, incisional or core needle (≤18-gauge).

Inclusion Criteria (Part 2 only)

  • Measurable disease meeting the following criteria:

    1. At least 1 lesion of ≥ 1.0 centimeters (cm) in the longest diameter for a non-lymph node or ≥ 1.5 cm in the short-axis diameter for a lymph node that is measurable according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 using computerized tomography/magnetic resonance imaging.
    2. Lesions that have had external beam radiotherapy or locoregional therapies such as radiofrequency ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.

      Inclusion Criteria (Part 2: triple negative breast cancer [TNBC] cohort only)

  • Histologically or cytologically confirmed diagnosis of TNBC.
  • Female participants who had received at least an anthracycline or taxane treatment for the neoadjuvant/adjuvant or chemotherapy for refractory or relapse TNBC and progressed radiographically.

Inclusion Criteria (Part 2: Type 2 endometrial carcinoma cohort only)

  • Histologically or cytologically confirmed diagnosis of Type 2 endometrial carcinoma (non-estrogen-dependent adenocarcinoma. However, carcinosarcoma and sarcoma are excluded).
  • Participants who had received at least one prior platinum-based chemotherapeutic regimen for advanced or metastatic endometrial carcinoma.

Exclusion Criteria:

  • Medical history of clinically significant cardiovascular impairment:

    1. Congestive heart failure greater than or equal to New York Heart Association Class III.
    2. Unstable angina pectoris, myocardial infarction or stroke within 6 months before of the first administration of the study drug.
    3. Prolongation of corrected QT (QTc) interval to > 480 milliseconds (ms) (Fridericia method).
    4. Arrhythmias requiring treatment.
  • Concomitant systemic infection requiring medical treatment.
  • Participants who test positive for human immunodeficiency virus (HIV antibody).
  • Active viral hepatitis (B or C) (*) as demonstrated by positive serology or requiring treatment.

(*) hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs)/hepatitis B core antibody (HBcAb), and anti-hepatitis C virus (HCV) antibody test. Participants who are anti-HBs/HBcAb (+) without detectable hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) are eligible.

  • Effusion requiring drainage continually.
  • Participants whose toxicity of previous treatment has not recovered to Grade 1 or lower (except for alopecia).
  • Participants who have received a previous monoclonal antibody therapy and have evidence of an immune or allergic serious reaction.
  • Participants who had previous treatment with other folate receptor targeting agents.
  • Participants who have medical history of discontinuing prior eribulin due to toxicity.
  • Other active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months prior to the first administration of the study drug.
  • Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin or human chorionic gonadotropin). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 3 days before the first administration of the study drug (breastfeeding participants are not eligible even if they discontinue breastfeeding).
  • Women of childbearing potential or man of impregnate potential who don't agree that both the participant and his/her partner will use a medically effective method for contraception (as below) during the study and after study drug discontinuation (male; 90 days, female; 60 days).

Note: Condom*, contraceptive sponge**, foam**, jelly**, diaphragm*, intrauterine device*, or use of oral contraception* from at least 4 weeks before starting the study treatment (*Approved drugs or certified medical devices in Japan, **Non-approved drugs or certified medical devices in Japan).

  • Known intolerance to the study drug or any of the excipients.
  • Any medical or other condition that in the opinion of the investigator(s) would preclude the subject's participation in the study.
  • Scheduled for surgery during the study.
  • Diagnosed with meningeal carcinomatosis.
  • 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 (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
  • Use of illegal recreational drugs.

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): NCT03386942


Contacts
Contact: Customer Joy Department. EJ 81-3-3817-3700 CLNCL@hhc.eisai.co.jp

Locations
Japan
Eisai Trial Site Recruiting
Tokyo, Japan, 104-0045
Sponsors and Collaborators
Eisai Inc.

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT03386942     History of Changes
Other Study ID Numbers: MORAb-202-J081-101
First Posted: December 29, 2017    Key Record Dates
Last Update Posted: May 28, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Eisai Inc.:
Solid Tumors
Folate Receptor α (FRA)-Positive Triple Negative Breast Cancer
FRA-Positive Type 2 Endometrial Carcinoma