Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence

NCT04013672 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CASE6318
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to assess the clinical activity of Pembrolizumab and SurVaxM in participants with recurrent glioblastoma.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Assess clinical activity of Pembrolizumab and SurVaxM in patients with recurrent glioblastoma using PFS at 6 months (PFS-6)

  6 months from start of treatment

Secondary Outcomes (1)

• Safety and Tolerability of Pembrolizumab and SurVaxM as Measure by CTCAE v 5 Grading as Per NCI

  up to 1 year from enrollment

Study Arms (2)

Arm A - Have not received immunotherapy

EXPERIMENTAL

Arm A is patients with first recurrence of glioblastoma who have failed prior chemotherapy and radiation but have not received any immunotherapy.

Drug: Pembrolizumab; Drug: SurVaxM; Drug: Sargramostim; Drug: Montanide ISA 51

Arm B - Have failed prior anti-PD1 therapy

EXPERIMENTAL

Arm B is an exploratory arm of 10 patients who have failed prior anti-PD1 therapy.

Drug: Pembrolizumab; Drug: SurVaxM; Drug: Sargramostim; Drug: Montanide ISA 51

Interventions

Pembrolizumab DRUG

200 mg IV every 3 weeks

Arm A - Have not received immunotherapy; Arm B - Have failed prior anti-PD1 therapy

SurVaxM DRUG

500 mcg per dose, dosed every two weeks for 4 doses and then every 3 months

Also known as: SVN53-67, M57-KLH

Arm A - Have not received immunotherapy; Arm B - Have failed prior anti-PD1 therapy

Sargramostim DRUG

100 mcg per dose, dosed every two weeks for 4 doses and then every 3 months

Also known as: GM-CSF

Arm A - Have not received immunotherapy; Arm B - Have failed prior anti-PD1 therapy

Montanide ISA 51 DRUG

1 ml per dose dosed every two weeks for 4 doses and then every 3 months

Arm A - Have not received immunotherapy; Arm B - Have failed prior anti-PD1 therapy

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of World Health Organization Grade IV glioma (glioblastoma or gliosarcoma)
• Previous first line treatment with at least radiotherapy with or without temozolomide
• Documented first recurrence of GBM by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI) performed within 21 days of randomization per RANO criteria.
• If first recurrence of GBM is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either:
• \-- Histopathologic confirmation of recurrent tumor, or
• \-- New enhancement on MRI outside of the radiotherapy treatment field
• Karnofsky performance status of 70 or higher or ECOG 0-2
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study drug.
• Previous treatment with anti PD1 will be allowed only in the exploratory arm
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archive tissue
• Screening/Baseline laboratory values must meet the following criteria (laboratory value):
• Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
• Hematological system:
• Absolute neutrophil count (ANC) ≥1500/uL

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1 (except in the exploratory arm), anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to (randomization /allocation).
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 2 mg daily of dexamethasone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Patients that likely to have the potential risk of cerebral edema due to inflammation related to SurVaxM and pembrolizumab and will exclude patients with \> 1 cm midline shift on imaging. Patients ust not have cerebral edema requiring more than 2 mg of daily of dexamethasone equivalent.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• More than one recurrence of GBM
• Presence of extracranial metastatic or leptomeningeal disease
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• 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.

Sponsors & Collaborators

• David Peereboom: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

pembrolizumab; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; montanide ISA 51

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: David Peereboom, MD
• Organization: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

TaussigResearch@ccf.org

1-866-223-8100

Study Officials

• David Peereboom, MD

  Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Principal Investigator

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 10, 2019
• Study Start: March 19, 2020
• Primary Completion: August 16, 2021
• Study Completion: February 16, 2022
• Last Updated: August 28, 2024
• Results First Posted: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

US (1)