Phase 2 Study of Sym004 for Adult Patients With Recurrent Glioblastoma

NCT02540161 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Pro00063483
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the activity of Sym004, a recombinant antibody mixture that specifically binds to EGFR, in patients diagnosed with recurrent glioblastoma whose tumor is EGFR amplified. This is a phase 2 study that will accrue patients with WHO grade IV recurrent malignant glioma (glioblastoma or gliosarcoma) in two cohorts to assess the efficacy of Sym004.

Conditions

Malignant Glioma

Keywords

Sym004; Glioblastoma; Desjardins; Pro00063483; Symphogen; Duke Cancer Institute

Outcome Measures

Primary Outcomes (1)

• Six-month Progression-free Survival (PFS6)

  Within each cohort, the percentage of participants alive and progression-free at 6 months after the start of Sym004 treatment will be determined. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival.

  6 months

Secondary Outcomes (4)

• Percentage of Participants Who Experience Grade 3, 4 or 5 Adverse Events

  2 years

• Radiographic Response

  2 years

• Median Progression-free Survival (PFS)

  2 years

• Median Overall Survival (OS)

  2 years

Study Arms (4)

non-bevacizumab failures - 18 mg/kg

EXPERIMENTAL

Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks.

Drug: Sym004 - 18 mg/kg

bevacizumab failures - 18 mg/kg

EXPERIMENTAL

Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks.

Drug: Sym004 - 18 mg/kg

non-bevacizumab failures - 24 mg/kg

EXPERIMENTAL

Non-bevacizumab failure (either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable for at least 6 months from prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen) will receive Sym004 intravenously every two weeks.

Drug: Sym004 - 24 mg/kg

bevacizumab failures - 24 mg/kg

EXPERIMENTAL

Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment) will receive Sym004 intravenously every two weeks.

Drug: Sym004 - 24 mg/kg

Interventions

Sym004 - 18 mg/kg DRUG

Sym004 was dosed at 18 mg/kg intravenously every two weeks.

bevacizumab failures - 18 mg/kg; non-bevacizumab failures - 18 mg/kg

Sym004 - 24 mg/kg DRUG

Beginning in August 2017, the dose was increased to 24 mg/kg intravenously every two weeks.

bevacizumab failures - 24 mg/kg; non-bevacizumab failures - 24 mg/kg

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed diagnosis of World Health Organization (WHO) grade 4 malignant glioma and radiographic evidence of recurrence or disease progression (as defined by the Response Assessment in Neuro-Oncology (RANO) criteria as a greater than 25% increase in the largest bi-dimensional product of enhancement or a new enhancing lesion, or a significant increase in T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) abnormality without another co-morbid cause);
• Age ≥ 18 years;
• Karnofsky Performance Status ≥ 70%;
• No more than 3 prior progressions;
• Cohort 1 only: Non-bevacizumab failure, i.e. either no prior bevacizumab or bevacizumab stable/responder, which is defined as stable within 6 months of prior treatment with bevacizumab without experiencing a bevacizumab adverse event of special interest (AESI) while on a bevacizumab-containing regimen, such as:
• ≥ grade 3 hypertension not controlled by medication, hypertensive crisis, or hypertensive encephalopathy
• ≥ grade 3 proteinuria that does not resolve or nephrotic syndrome
• Any grade GI perforation
• ≥ grade 3 infusion-related reaction
• ≥ grade 3 woundhealing complications
• ≥ grade 3 hemorrhage or any grade central nervous system (CNS) hemorrhage or ≥ grade 2 hemoptysis
• Any grade arterial thromboembolic event (e.g. myocardial infarction or cerebral infarction) or ≥ grade 3 venous thromboembolic event
• Any grade posterior reversible encephalopathy syndrome (PRES)
• ≥ grade 3 congestive heart failure
• ≥ grade 2 non-gastrointestinal (GI) abscesses and fistulae;

You may not qualify if:

• Pregnancy or breastfeeding;
• Prior treatment with EGFR-targeted therapy, including, but not limited to, the following examples: Gilotrif® (afatinib),Tarceva® (erlotinib), Erbitux® (cetuximab), Iressa™ (gefitinib), Vectibix® (panitumumab), Caprelsa® (vandetanib), Tykerb® (lapatinib), CDX110, D2C7-immunotoxin;
• Active infection requiring intravenous antibiotics within 7 days before enrollment;
• Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
• Less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation;
• Treated with immunotherapeutic agents, vaccines, or Mab therapy within 4 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy
• Treated with alkylating agents within 4 weeks (6 weeks for nitrosoureas) before enrollment or treated within 1 week before enrollment with daily or metronomic chemotherapy, unless the patient has recovered from the expected toxic effects of such therapy to their baseline or to grade 1;
• Prior treatment (non-alkylating agents) within 2 weeks before enrollment, unless the patient has recovered from the expected toxic effects of such therapy;
• Known hypersensitivity reactions to any of the components of Sym004;
• Known current drug abuse or alcohol abuse;
• Known Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection. Testing is not required as part of this study.

Sponsors & Collaborators

• Annick Desjardins: lead
• Symphogen A/S: collaborator

Study Sites (1)

The Preston Robert Tisch Brain Tumor Center

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke
• Duke Cancer Institute

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

futuximab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Results Point of Contact

• Title: Principal Investigator
• Organization: Duke University Medical Center

dukebrain1@duke.edu

9196845301

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: September 1, 2015
• First Posted: September 3, 2015
• Study Start: February 1, 2016
• Primary Completion: July 10, 2019
• Study Completion: April 27, 2020
• Last Updated: August 5, 2020
• Results First Posted: July 24, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)