Pembrolizumab and a Vaccine (ATL-DC) for the Treatment of Surgically Accessible Recurrent Glioblastoma

NCT04201873 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 19-001090NCI-2019-07994
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and how well of pembrolizumab and a vaccine therapy (ATL-DC vaccine) work in treating patients with glioblastoma that has come back (recurrent) and can be removed by surgery (surgically accessible). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Vaccines, such as ATL-DC vaccine, may help the body build an effective immune response to kill tumor cells. Giving pembrolizumab and ATL-DC vaccine may work better in treating patients with glioblastoma compared to ATL-DC alone.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (3)

• Cell cycle-related signature

  Up to 6 years

• Expansion of T cell receptor (TCR) clones

  Two-sample T-test with Bonferroni adjustment will be used to compare the increase number of expanded TCR clones after dendritic cell (DC) vaccination with PD-1 blockade in Group A versus (vs) DC vaccination with a placebo in Group B.

  Up to 6 years

• Incidence of adverse events (AEs)

  Adverse events will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. All patients who receive any amount of pembrolizumab/placebo or ATL-DC vaccination will be evaluable for toxicity, serious adverse events (SAEs), and events of clinical interest (ECIs).

  Up to 30 days post treatment

Secondary Outcomes (2)

• 6 month progression-free survival (PFS6)

  At 6 months

• Overall survival (OS)

  Up to 6 years

Other Outcomes (7)

• Biomarker analysis

  Up to 6 years

• TIL (tumor infiltrating lymphocyte) density and TCR (T cell receptor) Clonality in the tumor quantitatively measured by next generation TCR sequencing

  from baseline to surgery

• TIL density and TCR Clonality in the peripheral blood quantitatively measured by next generation TCR sequencing

  from baseline to surgery and post surgery treatment period, up to 24 months

Study Arms (2)

Group A (pembrolizumab, ATL-DC, poly ICLC)

EXPERIMENTAL

Beginning 14 days prior to scheduled surgery, patients receive pembrolizumab IV over 30 minutes. After surgery, patients receive pembrolizumab IV over 30 minutes on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

Biological: Dendritic Cell Tumor Cell Lysate Vaccine; Biological: Pembrolizumab; Drug: Poly ICLC

Group B (placebo, ATL-DC, poly ICLC)

ACTIVE COMPARATOR

Beginning 14 days prior to scheduled surgery, patients receive placebo IV. After surgery, patients receive placebo IV on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity.

Biological: Dendritic Cell Tumor Cell Lysate Vaccine; Other: Placebo Administration; Drug: Poly ICLC

Interventions

Dendritic Cell Tumor Cell Lysate Vaccine BIOLOGICAL

Given ID

Also known as: DC tumor cell lysate vaccine, dendritic cell-pulsed tumor cell lysate vaccine

Group A (pembrolizumab, ATL-DC, poly ICLC); Group B (placebo, ATL-DC, poly ICLC)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Group A (pembrolizumab, ATL-DC, poly ICLC)

Placebo Administration OTHER

Given IV

Group B (placebo, ATL-DC, poly ICLC)

Poly ICLC DRUG

Given IM

Also known as: Hiltonol, Poly I:Poly C with Poly-L-Lysine Stabilizer, poly-ICLC, PolyI:PolyC with Poly-L-Lysine Stabilizer, Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose, Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose, Stabilized Polyriboinosinic/Polyribocytidylic Acid

Group A (pembrolizumab, ATL-DC, poly ICLC); Group B (placebo, ATL-DC, poly ICLC)

Eligibility Criteria

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

You may qualify if:

• Participants with histologically confirmed diagnosis of surgically accessible recurrent/progressive glioblastoma will be enrolled in this study
• 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)
• Must be undergoing surgery that is clinically indicated, and eligible for resection with the expectation that the surgeon is able to resect at least 2 gram of tumor for lysate and research with low risk of inducing neurological injury
• A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
• A female participant who has childbearing potential must have negative urine or serum pregnancy test 72 hrs prior to the first dose and be willing to use adequate method of contraception for course of study and 120 days after last dose
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial
• Have unequivocal evidence for contrast enhancing tumor progression by RANO criteria based on MRI scan within 14 days prior to randomization
• Have a minimum tumor size of 2 x 2 cm\^2 based on MRI scan prior to surgery
• An interval of the following durations prior to randomization:
• At least 28 days from prior surgical resection
• At least 7 days from prior stereotactic biopsy
• At least 12 weeks from prior radiotherapy, unless there is unequivocal histologic confirmation of tumor progression
• At least 23 days from prior chemotherapy
• At least 42 days from nitrosureas
• Have sufficient archival tumor tissue confirming glioblastoma or variants for submission following registration. The following amount of tissue is required: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 10 FFPE ,unstained slides (5um thick)

You may not qualify if:

• A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to randomization. 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, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137)
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to randomization
• Note: Participants must have recovered from all adverse events (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 prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
• 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-guerin (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 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
• 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
• Has known tumor primarily localized to the brainstem or spinal cord
• 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Merck Sharp & Dohme LLC: collaborator
• Phase One Foundation: collaborator
• Oncovir, Inc.: collaborator

Study Sites (1)

Quan

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

pembrolizumab; poly ICLC

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

Study Officials

• Timothy F Cloughesy

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2019
• First Posted: December 17, 2019
• Study Start: January 8, 2020
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: August 22, 2025

Record last verified: 2025-08

Locations

US (1)