Study of Pembrolizumab and M032 (NSC 733972)

NCT05084430 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-30000775658006
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I (Cohort I and Cohort II) and Phase II trial is designed to confirm the safety and tolerability of Pembrolizumab when given in conjunction with M032, an Oncolytic Herpes Simplex Virus (oHSV) that expresses IL-12 and perform the Phase II portion using a Recommended Phase 2 Dose (RP2D) of M032 (provided by the Phase I) when given in conjunction with Pembrolizumab for recurrent malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, or glio-sarcoma).

Conditions

Glioblastoma Multiforme; Anaplastic Astrocytoma; Gliosarcoma

Keywords

Recurrent; Progressive; M032; Pembrolizumab

Outcome Measures

Primary Outcomes (4)

• Overall Survival at 12 and 24 months

  Overall Survival at 12 and 24 months allows for a quantifiable outcome that should be straightforward to compare to historical data in this patient population.

  12-24 months

• Progression Free Survival at 6 months (PFS-6)

  PFS-6 evaluates all treated patients at 6 months after baseline MRI and determines the percentage of patients who have not progressed by either imaging or neurologic evaluation. The iRA-NO criteria will be utilized to determine progression for this trial. PFS-6 will also be compared to historical controls for each cohort.

  6 months

• Overall Survival (OS)

  OS will be determined for each cohort of patients and compared to historical controls for that cohort. .

  3 years

• Progression Free Survival (PFS)

  PFS will be determined by MRI and neurologic evaluation using the iRANO criteria. PFS utilizes an historical approach to determining if progression has occurred and is helpful measure to compare this current study to historical studies. An important limitation in the assessment of PFS centers on the fact that patients may not get imaging or neurologic examinations done at an optimal or consistent time; as such, another approach, PFS-6, has been adopted in some studies. PFS-6 evaluates all treated patients at 6 months after baseline MRI and determines the percentage of patients who have not progressed by either imaging or neurologic evaluation. The iRANO criteria will be utilized to determine progression for this trial. PFS and OS will be compared to historical controls for each cohort.

  3 years

Study Arms (2)

Recurrent MG

EXPERIMENTAL

To determine the safety and tolerability of M032 at the doses examined when given in combinations with pembrolizumab in patients with recurrent MG.

Drug: M032; Drug: Pembrolizumab

Newly Diagnosed MG

EXPERIMENTAL

To determine Overall Survival at 12 and 24 months, and Progression Free Survival at 6 months (PFS-6) in patients with newly diagnosed glioblastoma multiforme of M032 when given in combinations with pembrolizumab (while maintaining safety).

Drug: M032; Drug: Pembrolizumab

Interventions

M032 DRUG

Starting at week four, patients will undergo treatment on the same day, and every three weeks thereafter, with intravenous infusion of 200mg of Pembrolizumab . A total of 3 combined doses of Pembrolizumab and M032 will be given.

Newly Diagnosed MG; Recurrent MG

Pembrolizumab DRUG

Starting at week four, patients will undergo treatment on the same day, and every three weeks thereafter, with intravenous infusion of 200mg of Pembrolizumab . A total of 3 combined doses of Pembrolizumab and M032 will be given.

Newly Diagnosed MG; Recurrent MG

Eligibility Criteria

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

You may qualify if:

• Phase I/Cohort I: Participants are eligible to be included in the study only if all of the following criteria apply:
• Patients must have histologically or cytologically confirmed glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma, and is deemed a potential candidate for resection of the recurrent tumor.
• Prior therapy: Patients must have failed external beam radio-therapy to the brain, and if eligible and tolerated, undergone appropriate treatment with temozolomide chemotherapy. All radiation and additional chemotherapies must have been completed at least 4 weeks prior to enrollment. Prior therapy with nitrosoureas must have been completed at least 6 weeks prior to enrollment.
• Phase I/Cohort II or Phase II: Participants are eligible to be included in the study only if all of the following criteria apply:
• Patient must have MRI findings consistent with probable malignant glioma, have no previous diagnosis of glioma, and have had either no history of any surgery for brain tumor. The exception to this requirement is that patients who have under-gone biopsy for diagnosis only and have not received any other treatment. All patients must be potential candidates for resection of the probably malignant glioma tumor.
• Should a patient in Phase I/Cohort II or Phase II be found on final pathologic diagnosis to not have a glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma, he/she will receive no other doses of M032 other than that administered at the time of craniotomy, nor will he/she receive any doses of Pembrolizumab. He/she will be followed for evidence of toxicity of M032 only and will be considered off-study for all efficacy and other secondary endpoints.

You may not qualify if:

• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of M032 in patients \<16 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials.
• Karnofsky Performance Status (KPS) ≥70% (see Appendix B).
• Life expectancy of greater than 4 weeks.
• Preoperatively, the lesion must be ≥1.0 cm in diameter as determined by MRI.
• The effects of M032 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for six months after receiving the final dose of M032. Because it is currently unknown if M032 can be transmitted by sexual contact, a barrier method of birth control must be employed and for six (6) months following the administration of the last dose of this study drug. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. Subjects should also refrain from donating blood during the trial.
• Ability to understand and the willingness to sign a written informed con-sent document.
• Females of childbearing potential must not be pregnant; this will be con-firmed by a negative serum pregnancy test within 14 days prior to starting study treatment.
• Patients must have normal organ and marrow function as defined below:
• leukocytes……………………. \>3,000/μl
• absolute neutrophil count………. \>1,500/μl
• platelets…………………………... \>100,000/μl
• total bilirubin……………………. within normal institutional limits
• AST(SGOT)/ALT(SGPT)………… \<2.5 X institutional upper limit of normal creatinine within normal institutional limits Or
• creatinine clearance……………... \>60 mL/min/1.73 m2 for patients with creatinine levels above insti-tutional normal
• A Woman of Child Bearing Potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to allocation.(see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Gliosarcoma; Recurrence

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• James Markert, MD

  The University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Markert, MD

CONTACT

2059343411; jmarkert@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Department of Neurosurgery

Model Details: Recurrent Newly Diagnosed

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: October 19, 2021
• Study Start: February 25, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)