Study Evaluating ABT-414 in Japanese Subjects With Malignant Glioma

A Non-Randomized, Open-Label, Multi-Center Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Japanese Subjects With Malignant Glioma

This study seeks to evaluate the tolerability, pharmacokinetics (PK), efficacy, and safety of ABT-414 in Japanese participants with newly diagnosed and recurrent, World Health Organization (WHO) grade III or IV malignant glioma.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme; Malignant Glioma
• Intervention / Treatment: Drug: ABT-414; Drug: Temozolomide; Radiation: Whole Brain Radiation

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 260-0801
    • Chiba Cancer Center /ID# 164375
  • Kyoto, Japan, 612-0861
    • NHO Kyoto Medical Center /ID# 140437
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute /ID# 148494
  • Aichi
    • Nagoya-shi, Aichi, Japan, 466-8560
      • Nagoya University Hospital /ID# 138559
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 734-8551
      • Hiroshima University Hospital /ID# 139399
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital /ID# 150589
  • Ibaraki
    • Tsukuba-shi, Ibaraki, Japan, 305-8576
      • University of Tsukuba Hospital /ID# 140433
  • Iwate
    • Shiwa-gun, Iwate, Japan, 028-3695
      • Iwate Medical University Hospital /ID# 149145
  • Kanagawa
    • Sagamihara-shi, Kanagawa, Japan, 252-0375
      • Kitasato University Hospital /ID# 148493
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 860-8556
      • Kumamoto University Hospital /ID# 138558
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • Kyoto Prefect Univ Med /ID# 149093
    • Kyoto-shi, Kyoto, Japan, 606-8507
      • Kyoto University Hospital /ID# 163206
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 980-8574
      • Tohoku University Hospital /ID# 138464
  • Okayama
    • Okayama-shi, Okayama, Japan, 700-8558
      • Okayama University Hospital /ID# 148674
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0871
      • Osaka University Hospital /ID# 140438
  • Saitama
    • Hidaka-shi, Saitama, Japan, 350-1298
      • Saitama Medical University International Medical Center /ID# 140361
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center /ID# 148673
  • Tochigi
    • Shimotsuga-gun, Tochigi, Japan, 321-0293
      • Dokkyo Medical University Hospital /ID# 150990
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 140435
    • Itabashi-ku, Tokyo, Japan, 173-0032
      • Nihon University Itabashi Hospital /ID# 149385
    • Mitaka-shi, Tokyo, Japan, 181-8611
      • Kyorin University Hospital /ID# 140360
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Tokyo Women's Medical University Hospital /ID# 140436

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Japanese participants with WHO grade III or IV malignant glioma
• 70 or above on Karnofsky Performance Status in Arm A of Phase 1 portion and Phase 2 portion
• 80 or above on Karnofsky Performance Status in Arm B and Arm C of Phase 1 portion
• Adequate bone marrow function
• Recurrent malignant glioma per RANO criteria in Arm A of Phase 1 portion and Phase 2 portion
• Histologically proven newly diagnosed malignant glioma in Arm B and Arm C of Phase 1 portion
• Participants must have confirmed EGFR amplification by central lab in Phase 2 portion

Exclusion Criteria:

• Anti-cancer treatment 28 days prior to study Day 1 for Arm A of Phase 1 portion and Phase 2 portion (except temozolomide therapy for newly diagnosed treatment for Phase 2 portion)
• Anti-cancer treatment prior to study Day 1 for Arm B and Arm C of Phase 1 portion
• Participant has received prior treatment with bevacizumabor, EGFR therapy in Arm A of Phase 1 portion and Phase 2 portion, or for recurrent glioblastoma in Phase 2 portion
• Participant has a history of major immunologic reaction to any Immunoglobulin G containing agents or component of ABT-414.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A of Phase 1 portion; ABT-414 administered every other weeks monotherapy	Drug: ABT-414; ABT-414 will be administered by intravenous infusion; Other Names: Depatuxizumab; Mafodotin
Experimental: Phase 2 portion; ABT-414 administered every other weeks in combination with temozolomide	Drug: ABT-414; ABT-414 will be administered by intravenous infusion; Other Names: Depatuxizumab; Mafodotin; Drug: Temozolomide; Temozolomide will be administered per label.
Experimental: Arm C of Phase 1 portion; ABT-414 administered every other weeks in combination with radiation and temozolomide	Drug: ABT-414; ABT-414 will be administered by intravenous infusion; Other Names: Depatuxizumab; Mafodotin; Drug: Temozolomide; Temozolomide will be administered per label.; Radiation: Whole Brain Radiation; Whole Brain Radiation will be administered in over 30 fractions as per the procedure in each study site.
Experimental: Arm B of Phase 1 portion; ABT-414 administered every other weeks in combination with radiation and temozolomide	Drug: ABT-414; ABT-414 will be administered by intravenous infusion; Other Names: Depatuxizumab; Mafodotin; Drug: Temozolomide; Temozolomide will be administered per label.; Radiation: Whole Brain Radiation; Whole Brain Radiation will be administered in over 30 fractions as per the procedure in each study site.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with adverse events		At each visit for approximately 4 years
Number of Dose Limiting Toxicities	Measurement by clinical lab results, vital signs, physical exam and electrocardiogram (ECG) during the Phase 1 portion of the study.	At each visit for approximately 1 year
Progression-free survival	Time to progression-free survival is defined as the number of days from the date of first dose to the date of earliest disease progression based on Response Assessment in Neuro-Oncology (RANO) criteria or to the date of death, if disease progression does not occur (except Arm B and Arm C of Phase 1 portion).	At each visit for approximately 1 year
Area under the plasma concentration-time curve (AUC) of ABT-414	Assessed during the Phase 1 portion of the study, the area under the plasma concentration-time curve (AUC) is a method of measurement to determine the total exposure of a drug in blood plasma.	Multiple time points in Cycles 1, 2 and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment for approximately 1 year for recurrent subjects and in every week of Day 1 until Week 7 and end of treatment for the newly diagnosed subjects
Maximum plasma concentration (Cmax) of ABT-414	Assessed during the Phase 1 portion of the study, the maximum plasma concentration (Cmax) is the highest concentration that a drug achieves in the blood after administration in a dosing interval.	Multiple time points in Cycles 1, 2 and 3 (4 weeks each) and Day 1 of remaining cycles until end of treatment for approximately 1 year for recurrent subjects and in every week of Day 1 until Week 7 and end of treatment for the newly diagnosed subjects

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The objective response rate is defined as the proportion of participants with at least one measurable lesion at baseline who achieves a confirmed complete (CR) or partial response (PR) based on RANO criteria (except Arm B and Arm C of Phase 1 portion).	At each visit for approximately 1 year
Overall Survival	Overall survival is defined as number of days from the date of first dose to the date of death for all dosed participants (except Arm B and Arm C of Phase 1 portion).	At each visit for approximately 1 year
Duration of Overall Response	The duration of overall response for a given participant is defined as the number of days from the day the RANO criteria are met for CR or PR (whichever is recorded first) to the date that progressive disease (PD) is objectively documented (based RANO criteria) (except Arm B and Arm C of Phase 1 portion).	At each visit for approximately 1 year

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Narita Y, Muragaki Y, Kagawa N, Asai K, Nagane M, Matsuda M, Ueki K, Kuroda J, Date I, Kobayashi H, Kumabe T, Beppu T, Kanamori M, Kasai S, Nishimura Y, Xiong H, Ocampo C, Yamada M, Mishima K. Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial. Cancer Sci. 2021 Dec;112(12):5020-5033. doi: 10.1111/cas.15153. Epub 2021 Oct 30.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2015
• Primary Completion (Actual): August 27, 2020
• Study Completion (Actual): August 27, 2020

Study Registration Dates

• First Submitted: September 28, 2015
• First Submitted That Met QC Criteria: October 27, 2015
• First Posted (Estimate): October 29, 2015

Study Record Updates

• Last Update Posted (Actual): September 3, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Glioblastoma; WHO grade III; WHO grade IV
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: M13-714

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• 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