ASP8374 + Cemiplimab in Recurrent Glioma

NCT04826393 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 21-054
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

Brief Summary

This study is looking at the safety and efficacy of the drug combination of ASP8374 with cemiplimab in people with recurrent malignant glioma. The study will be conducted in two parts, the first portion of the study will be to establish the highest dose of ASP8374 that can be given safely with cemiplimab and will be used as the recommended dose of ASP8374 in combination with cemiplimab for the second portion of the study. The second portion of the study will be to compare the effect of having ASP8374 in combination with cemiplimab prior to surgery. The names of the study drugs involved in this study are:

• ASP8374
• Cemiplimab

Conditions

Glioblastoma; Recurrent Glioblastoma

Keywords

Glioblastoma; Recurrent Glioblastoma; Glioma, Grade 3

Outcome Measures

Primary Outcomes (2)

• Maxium Tolerated Dose-MTD/ Phase 2 Recommend Dose-RP2D - Cohort 1

  primary endpoint for Cohort 1 will be determination of the MTD/RP2D of ASP8374 when administered with cemiplimab among recurrent malignant glioma participants.

  Enrollment up to 2 years

• CD8+ TIL Tumor Density-Cohort 2

  CD8+ TIL density from tumors obtained from participants randomized to the neoadjuvant study arm (2A) will be compared to tumor CD8+ TIL density obtained from control participants enrolled on Arm 2B who do not receive neoadjuvant therapy.

  Enrollment up to 2 years

Secondary Outcomes (3)

• Rate of Adverse Events

  Enrollment up to 2 years

• progression-free survival (PFS)

  6 months

• overall survival (OS).

  12 months

Study Arms (2)

ASP8374 and Cemiplimab-Cohort 1

EXPERIMENTAL

A 3+3 dose escalation design will be used to determine maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ASP8374 when combined with cemiplimab. Participants will receive ASP8374 and Cemiplimab every 3 weeks for up to 2 years. ASP8374 will be available until October 31, 2022. Subjects may continue treatment with cemiplimab alone after that date.

Drug: ASP8374; Drug: cemiplimab

ASP8374 and Cemiplimab-Cohort 2

EXPERIMENTAL

Upon determination of the MTD/RP2D of ASP8374 plus cemiplimab in Cohort 1, a dose expansion will be performed in which eligible participants who are candidates for surgical resection will enroll to Cohort 2 and will be randomized into one of two treatment groups (2A-2B). Group 2A: IV ASP8374 plus cemiplimab within 14± 5 days prior to surgery at the MTD/RP2D established in Cohort 1. Group 2B: No immune checkpoint therapy prior to surgery. Post-operatively, all Cohort 2 participants will receive ASP8374 plus cemiplimab every 3 weeks administered at the MTD/RP2D established by Cohort 1

Drug: ASP8374; Drug: cemiplimab

Interventions

ASP8374 DRUG

every 3 weeks by intravenous infusion

ASP8374 and Cemiplimab-Cohort 1; ASP8374 and Cemiplimab-Cohort 2

cemiplimab DRUG

intravenous infusion

Also known as: Libtayo

ASP8374 and Cemiplimab-Cohort 1; ASP8374 and Cemiplimab-Cohort 2

Eligibility Criteria

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

You may qualify if:

• Have histologically confirmed WHO grade IV GBM or its variants. Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of GBM is made. Participants with WHO grade III recurrent malignant glioma will be allowed to enroll to Cohort 1 only.
• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a Karnofsky performance status (KPS) ≥ 70 (Appendix A).
• Previous first line therapy with at least radiotherapy.
• Be at first or second relapse. Note: Relapse is defined as progression following initial therapy (i.e., radiation ± chemotherapy). For participants who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse.
• Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 days of registration.
• Table 1: Adequate Organ Function Laboratory Values
• System Laboratory Value
• Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Renal Serum creatinine OR measured or calculated a creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X institutional upper limit of normal (ULN) OR
• ≥60 mL/min for participant with creatinine levels \> 1.5 X institutional ULN a Creatinine clearance should be calculated per institutional standard.
• Hepatic Serum total bilirubin ≤ 1.5 X institutional ULN OR Direct bilirubin ≤ institutional ULN for participants with total bilirubin levels \> 1.5 institutional ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X institutional ULN OR
• ≤ 5 X institutional ULN for participants with Gilberts syndrome Albumin \>2.5 mg/dL

You may not qualify if:

• Current or planned participation in a study of an investigational agent or using an investigational device.
• Has a diagnosis of immunodeficiency.
• Has tumor primarily localized to the brainstem or spinal cord.
• Has presence of diffuse leptomeningeal disease or extracranial disease.
• Has received systemic immunosuppressive treatments, aside from systemic corticosteroids as described in Section 3.2.7, (such as methotrexate, chloroquine, azathioprine, etc.) within six months of registration.
• Has received anti-VEGF or anti-VEGFR targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc.).
• Requires treatment with moderate or high dose systemic corticosteroids defined as dexamethasone \> 2 mg/day or bioequivalent for at least 3 consecutive days within 7 days of registration.
• Has received prior interstitial brachytherapy or stereotactic radiosurgery (Cohort 2 only).
• Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of registration.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade \> 3 within 6 months of registration.
• Has a known additional malignancy that is progressing or requires active treatment within 2 years of registration. Exceptions include malignancies treated with surgery alone including but not limited to basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. See Section 5.4.3 for additional information on allowed corticosteroid dosing.
• Has confirmed history or any evidence of active non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Regeneron Pharmaceuticals: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (4)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Hospital of the University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Glioblastoma; Glioma; Lymphoma, Follicular

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• David A Reardon, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 1, 2021
• Study Start: March 9, 2022
• Primary Completion: October 31, 2022
• Study Completion: January 1, 2024
• Last Updated: October 22, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (4)