A Phase 1 Study of MORAb-004 in Patients With Solid Tumor (Study: MORAb-004-J081-103)

A Phase 1 Study of MORAb-004 in Patients With Solid Tumor

This is a multicenter, multiple doses, open-label Phase 1 study of MORAb-004 in subjects with solid tumors. Subjects may have any solid tumor without intracranial involvement or metastases that has failed standard chemotherapy.

This study will be conducted in 2 parts: 1) Part 1 will be the dose escalation portion of this study to assess the tolerability and the safety profile of MORAb-004. Dose will escalate in different cohorts as follows: 2, 4, 8 and 12 mg/kg weekly dosing each as a 4-week cycle with no intra-subject escalation. Individual participants may have additional cycles at the same dose until disease progression unless the participants meet the discontinuation criteria.

2) Part 2 will comprise cohort expansions to further characterize the safety and tolerability of MORAb-004 and to assess preliminary efficacy and the pharmacokinetic/pharmacodynamic relationship of MORAb-004 in gastric cancer and hepatocellular carcinoma (HCC). Three dose levels will be expanded based on the safety profile that was obtained in the dose escalation portion of this study (Part 1): 4 mg/kg (administered on a weekly basis), 8 mg/kg (administered on a weekly basis) and 12 mg/kg (administered every OTHER week).

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: MORAb-004

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Chikusa-ku, Aichi, Japan
  • Chiba
    • Kashiwa, Chiba, Japan
  • Shizuoka
    • Nagaizumi-cho, Shizuoka, Japan
  • Tokyo
    • Chuo-ku, Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Provide written informed consent,
2. Japanese male and female subjects aged at 20 or older at informed consent,
3. Have malignant solid tumor, without intracranial involvement or metastasis, diagnosed by standard pathology criteria that has failed or are resistant to standard chemotherapy,
4. Performance status (PS) is 0 to 1 by Eastern Cooperative Oncology Group,
5. With no carry-over effect and no adverse drug reaction of prior treatment which may affect the safety evaluation of MORAb-004, except for Grade 1 or 2 neuropathy and alopecia,
6. Survival expectation is 12 weeks or longer after starting MORAb-004 administration

Exclusion criteria:

1. Have clinically significant cardiovascular disease,
2. Scheduled for laparotomic surgery due to trauma or other reasons for during the study,
3. Have clinically significant hemorrhagic event or history, or event with high risk of hemorrhage,
4. Receiving chronic systemic anticoagulation,
5. Have evidence of other active invasive malignancy
6. Females who are lactating or pregnant at Screening or Baseline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MORAb-004

Drug: MORAb-004; MORAb-004 5 mg/mL is administered as an intravenous infusion (IV) in an escalating dose design and will not be escalated or de-escalated in individual participants. Part 1 (Dose escalation): 4 weekly administrations of 2, 4, 8, and 12 mg/kg in four different cohorts on Days 1, 8, 15, and 22 of a 4-week cycle (28 days). Part 2 (Cohort expansion): 4 and 8 mg/kg on Days 1, 8, 15, and 22 of a 4-week cycle (28 days) and 12 mg/kg biweekly administration on Days 1 and 15 of a 4-week cycle in different cohorts. The dosages in Part 2 can be amended considering the results of Part 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability and Safety	Tolerability and the safety profile of multiple intravenous (IV) infusions of MORAb-004 in Japanese participants with solid tumors.	Up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)- Part I	Maximum tolerated dose (MTD) as defined by dose limiting toxicities (DLTs) within the administered range.	Up to 30 months
Optimal Biologic Dose (OBD)- Part II		Up to 30 months

Collaborators and Investigators

• Sponsor: Eisai Co., Ltd.
• Investigators: Study Director: Ryo Nakajima, Eisai Co., Ltd.

Publications and helpful links

General Publications

• Doi T, Aramaki T, Yasui H, Muro K, Ikeda M, Okusaka T, Inaba Y, Nakai K, Ikezawa H, Nakajima R. A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors. Invest New Drugs. 2019 Oct;37(5):1061-1074. doi: 10.1007/s10637-018-0713-7. Epub 2019 Jan 9.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: January 17, 2013
• First Submitted That Met QC Criteria: January 18, 2013
• First Posted (Estimate): January 23, 2013

Study Record Updates

• Last Update Posted (Estimate): November 10, 2016
• Last Update Submitted That Met QC Criteria: November 8, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: MORAb-004-J081-103