Clinical Trials /

A Study of MORAb-202 in Participants With Solid Tumors

NCT03386942

Description:

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

Related Conditions:
  • Breast Carcinoma
  • Endometrial Adenocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of MORAb-202 in Participants With Solid Tumors
  • Official Title: A Phase 1 Study of MORAb-202 in Subjects With Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: MORAb-202-J081-101
  • NCT ID: NCT03386942

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
MORAb-202MORAb-202

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
MORAb-202ExperimentalPart 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.
  • MORAb-202

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of participants with dose-limiting toxicities (DLTs)
Time Frame:At the end of Cycle 1 (21 days)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:Cmax is the maximum serum concentration of MORAb-202 after administration of the drug.
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:The RD will be determined based on the MTD, efficacy, and safety data in Part 1 and Part 2
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:ORR is defined as the percentage of participants with BOR of CR or PR.
Measure: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)
Safety Issue:
Description:DCR is defined as the percentage of participants with BOR of CR, PR, or SD.
Measure: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)
Safety Issue:
Description:CBR is defined as the percentage of participants with BOR of CR, PR or durable (SD) (duration of SD ≥ 23 weeks).
Measure:Part 2: Progression-free survival (PFS)
Time Frame:From the date of screening until disease progression or death (up to 22 months)
Safety Issue:
Description: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).
Measure:Part 2: Overall Survival (OS)
Time Frame:From the date of screening until the last observation visit (up to 22 months)
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Inc.

Trial Keywords

  • Solid Tumors
  • Folate Receptor α (FRA)-Positive Triple Negative Breast Cancer
  • FRA-Positive Type 2 Endometrial Carcinoma

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