A Pilot Surgical Trial To Evaluate Early Immunologic Pharmacodynamic Parameters For The PD-1 Checkpoint Inhibitor, Pembrolizumab (MK-3475), In Patients With Surgically Accessible Recurrent/Progressive Glioblastoma

NCT02852655 | Active Not Recruiting Phase 1 Results DMC

• 1 other identifier: 16-225
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 7

Brief Summary

This research study is studying an immunotherapy as a possible treatment for Glioblastoma.

Conditions

Brain Cancer

Keywords

Brain Tumor

Outcome Measures

Primary Outcomes (3)

• Tumor Infiltrating T Lymphocyte (TIL) Density

  To measure changes in tumor infiltrating T lymphocyte (TIL) density, defined as % total cells. It will be assessed using pooled Group A and Group B patients.

  2 weeks. TIL density is determined in surgical tumor tissue; on-study surgery occurs 14 days (+/- 5 days) after Neoadjuvant Day 1.

• Cell Cycle and Cancer Proliferation Genetic Signature

  To measure changes in cell cycle and cancer proliferation genetic signature; these results are reported using Gene Set Variation Analysis (GSVA) absolute enrichment scores (ES). GSVA scores are unit-less scores derived by comparing mRNA expression of a specific gene set to genes outside of the gene set in a sample. In this case, GSVA scores for "Farmers\_breast\_cancer\_cluster\_2, as previously described" were utilized. PMID 30742122 (https://pubmed.ncbi.nlm.nih.gov/30742122/) and PMID 23323831 (https://pubmed.ncbi.nlm.nih.gov/23323831/) It will be assessed using pooled Group A and Group B patients.

  2 weeks. Cell cycle/cancer proliferation genetic signature is determined in surgical tumor tissue; on-study surgery occurs 14 days (+/- 5 days) after Neoadjuvant Day 1.

• Incidence of Treatment-Emergent Adverse Events

  Number of Participants who Experienced a Serious Adverse Event (SAE) or Event of Clinical Interest (ECI) Deemed At Least Possibly Related to Pembrolizumab (MK3475). The following are measured as part of safety: laboratory safety assessments, KPS status, vital signs and physical examinations.

  5 years. Although there is still 1 patient on active study treatment as of today (4/1/2024), we stopped looking at this information as of 6/2/2022 for study reporting purposes.

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  180 Days

Study Arms (2)

Pre-surgery MK-3475

EXPERIMENTAL

-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK3475) pre-surgery at pre-determine dosage followed by Pembrolizumab at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously

Drug: MK-3475

No MK-3475 at Pre-Surgery

ACTIVE COMPARATOR

-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK-3475) at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously

Drug: MK-3475

Interventions

MK-3475 DRUG

Also known as: Pembrolizumab

No MK-3475 at Pre-Surgery; Pre-surgery MK-3475

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 World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma). Participants will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made.
• 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

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 (such as methotrexate, chloroquine, azathioprine, etc) within six months of registration.
• Has received anti-angiogenic or anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL-184, sunitinib, etc).
• Requires treatment with high dose systemic corticosteroids defined as dexamethasone \> 4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of registration.
• Has received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection or convection enhanced delivery.
• 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 3 years of registration. Exceptions include 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94143-0372, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan-Kettering Cancer

New York, New York, 10065, United States

Location

UT, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• McFaline-Figueroa JR, Sun L, Youssef GC, Huang R, Li G, Kim J, Lee EQ, Nayak L, Chukwueke U, Beroukhim R, Batchelor TT, Chiocca EA, Everson RG, Doherty L, Stefanik J, Partridge K, Spearman A, Myers A, Westergaard C, Russ A, Lavallee M, Smokovich A, LaForest-Roys C, Garcia Fox R, McCluskey C, Bi WL, Arnaout O, Peruzzi P, Cosgrove GR, Ligon KL, Arrillaga-Romany I, Clarke JL, Reardon DA, Cloughesy TF, Prins RM, Wen PY. Neoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort. Nat Commun. 2024 Dec 30;15(1):10757. doi: 10.1038/s41467-024-54326-7.

  PMID: 39737895 DERIVED

MeSH Terms

Conditions

Brain Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Jose R. McFaline Figueroa, MD, PhD
• Organization: Dana-Farber Cancer Institute

jose_mcfalinefigueroa@dfci.harvard.edu

617-632-2166

Study Officials

• Patrick Wen, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Patrick Wen, MD

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: August 2, 2016
• Study Start: September 21, 2016
• Primary Completion: June 2, 2022
• Study Completion (Estimated): July 31, 2026
• Last Updated: March 20, 2026
• Results First Posted: November 26, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)