A Study of MORAb-202 (Herein Referred to as Farletuzumab Ecteribulin) in Participants With Solid Tumors

NCT03386942 | Completed Phase 1

• 1 other identifier: MORAb-202-J081-101
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

Solid Tumors

Keywords

Solid Tumors; Folate Receptor α (FRA) and platinum-resistant ovarian carcinoma; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (9)

• Part 1: Number of participants with dose-limiting toxicities (DLTs)

  DLTs are defined as the following occurring in Cycle 1 for which a causal relationship with study drug cannot be ruled out: febrile neutropenia, Grade 4 neutropenia persisting for more than 7 days, or neutropenia requiring hematopoietic stimulating agents, Grade 4 thrombocytopenia, or thrombocytopenia requiring platelet transfusion, Grade 4 anemia, or anemia requiring blood transfusion, Grade 3 non-hematological toxicity (except abnormal clinical laboratory values of no clinical significance, any events which can be managed and controlled to Grade 2 or less by maximal medical management, infusion reactions of Grade 3 or higher are NOT considered DLTs because they are stochastic and idiosyncratic events, not related to dose), Grade 4 non-hematological toxicity, and/or when the second treatment with farletuzumab ecteribulin is postponed more than 14 days from the scheduled day due to toxicity. DLTs will be determined by discussion between the investigator, sponsor, and medical expert.

  At the end of Cycle 1 (21 days)

• Part 1 and Part 2: Number of participants with adverse events (AEs), adverse events of interest (AEIs), and serious adverse events (SAEs)

  Up to 50 months

• Number of participants with any clinically significant clinical laboratory test value

  Clinical significance will be determined by the Investigator.

  Up to 50 months

• Number of participants with any clinically significant vital sign value

  Clinical significance will be determined by the Investigator.

  Up to 50 months

• Change from Baseline in arterial oxygen saturation

  Baseline; up to 50 months

• Change from Baseline in body weight

  Baseline; up to 50 months

• Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value

  Clinical significance will be determined by the Investigator.

  Up to 50 months

• Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG)

  Baseline; up to 50 months

• Change from Baseline in serum anti-drug antibody (ADA) titer

  Baseline; up to 50 months

Secondary Outcomes (12)

• Part 1: Maximum Tolerated Dose (MTD) of Farletuzumab Ecteribulin

  21 days following each dose level of farletuzumab ecteribulin (up to a maximum of 50 months)

• Part 1 and Part 2: Maximum observed serum concentration (Cmax) of Farletuzumab Ecteribulin

  Predose; end of infusion; 0.5, 1, 2, 4, and 24 hours post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 50 months)

• Part 1 and Part 2: Maximum serum concentration of total antibody

  Predose; end of infusion; 0.5, 1, 2, 4, and 24 hours post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 50 months)

• Part 1 and Part 2: Plasma concentration of free eribulin

  Predose; end of infusion; 0.5, 1, 2, 4, and 24 hours post infusion on Day 1; on Days 4, 8, and 15; and the discontinuation and last observation visit (up to 50 months)

• Recommended dose (RD) of farletuzumab ecteribulin for future studies

  From the date of screening until the last observation visit (up to 50 months)

Study Arms (1)

Farletuzumab Ecteribulin

EXPERIMENTAL

Part 1 (Dose-escalation): The initial dose level of farletuzumab ecteribulin 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): farletuzumab ecteribulin 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: Farletuzumab Ecteribulin

Interventions

Farletuzumab Ecteribulin DRUG

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

Also known as: MORAb-202

Farletuzumab Ecteribulin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (or screening 2, in case of participants who enter this clinical study from screening 2).
• Part 1 only: Participants with FRA-positive solid tumor confirmed by immunohistochemistry (IHC) assay at the central laboratory using their available tumor samples from resected specimen (i.e., surgical or excisional/incisional biopsy samples) or core needle biopsy (\<=18-gauge), or participants with a histological and/or cytological diagnosis of any serous ovarian carcinoma, fallopian tube carcinoma, endometrial carcinoma, or adenocarcinoma of Non-Small Cell Lung Cancer (NSCLC), whose archival resected tumor samples (that is, surgical or excisional/incisional biopsy sample).
• Part 1 only: 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.
• Hemoglobin \>=9.0 grams per deciliter (g/dL).
• Neutrophil count \>=1.5 × 10\^3/microliters (μL).
• Platelet count \>=10 × 10\^4/μL.
• Total bilirubin \<=1.5 × upper limit of normal (ULN) in the facility.
• Alanine aminotransferase and aspartate aminotransferase \<=3.0 × ULN in the facility (in the case of liver metastases \<=5\*ULN).
• Serum creatinine \<=1.5 × ULN in the facility.
• 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.

You may not qualify if:

• Medical history of clinically significant cardiovascular impairment:
• Congestive heart failure greater than or equal to New York Heart Association Class III.
• Unstable angina pectoris, myocardial infarction or stroke within 6 months before of the first administration of the study drug.
• Prolongation of corrected QT (QTc) interval to \> 480 milliseconds (ms) (Fridericia method).
• Arrhythmias associated with hemodynamic instability.
• 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)/HCV- ribonucleic acid (RNA) are eligible.
• Effusion requiring drainage continually.
• Participants whose toxicity of previous treatment has not recovered to Grade 1 or lower (except for alopecia and hemoglobin).
• 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.
• Has an active pneumonitis/interstitial lung disease (ILD), a history of pneumonitis/ILD that required systemic steroids, received radiotherapy to lung field within 12 months before the first dose of study intervention, or current clinically relevant lung disease (example, Chronic Obstructive Pulmonary Disease).

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (10)

Eisai Trial Site 5

Matsuyama, Ehime, Japan

Location

Eisai Trial Site 6

Kurume, Fukuoka, Japan

Location

Eisai Trial Site 8

Sapporo, Hokkaido, Japan

Location

Eisai Trial Site 4

Akashi, Hyōgo, Japan

Location

Eisai Trial Site 7

Niigata, Niigata, Japan

Location

Eisai Trial Site 3

Hidaka, Saitama, Japan

Location

Eisai Trial Site 9

Sunto-gun, Shizuoka, Japan

Location

Eisai Trial Site 1

Chuo-ku, Tokyo, Japan

Location

Eisai Trial Site 10

Koto-Ku, Tokyo, Japan

Location

Eisai Trial Site 2

Koto-ku, Tokyo, Japan

Location

Related Publications (2)

• Yonemori K, Yunokawa M, Matsumoto K, Takehara K, Hasegawa K, Hirashima Y, Kato H, Ikezawa H, Otake Y, Yusa W, Miura T, Nishio S. Clinical trial of safety and antitumor activity of farletuzumab ecteribulin in patients with platinum-resistant ovarian cancer: Phase I expansion results. Int J Gynaecol Obstet. 2025 Dec 23. doi: 10.1002/ijgo.70676. Online ahead of print.

  PMID: 41432226 DERIVED

• Shimizu T, Fujiwara Y, Yonemori K, Koyama T, Sato J, Tamura K, Shimomura A, Ikezawa H, Nomoto M, Furuuchi K, Nakajima R, Miura T, Yamamoto N. First-in-Human Phase 1 Study of MORAb-202, an Antibody-Drug Conjugate Comprising Farletuzumab Linked to Eribulin Mesylate, in Patients with Folate Receptor-alpha-Positive Advanced Solid Tumors. Clin Cancer Res. 2021 Jul 15;27(14):3905-3915. doi: 10.1158/1078-0432.CCR-20-4740. Epub 2021 Apr 29.

  PMID: 33926914 DERIVED

MeSH Terms

Conditions

Pyogenic arthritis, pyoderma gangrenosum, and acne; Carcinoma, Non-Small-Cell Lung

Interventions

MORAb-202

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

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

Model Details: This is a Phase 1 study of farletuzumab ecteribulin 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 farletuzumab ecteribulin in participants with solid tumors. Considering efficacy, safety, and the pharmacokinetic (PK) profile, two doses may be selected from Part 1 for Part 2. Part 2 will comprise cohort expansions to further characterize the safety of farletuzumab ecteribulin and to evaluate the preliminary efficacy of farletuzumab ecteribulin in participants with FRA-positive platinum-resistant ovarian carcinoma and non-small cell lung cancer (NSCLC). The recommended dose for future studies will be determined based on the data from Part 1 and Part 2.

Study Record Dates

• First Submitted: November 28, 2017
• First Posted: December 29, 2017
• Study Start: November 28, 2017
• Primary Completion: October 26, 2022
• Study Completion: October 26, 2022
• Last Updated: November 28, 2022

Record last verified: 2022-11

Locations

JP (10)