Laser Interstitial Thermal Therapy (LiTT) With Cemiplimab or Other Chemotherapy in Recurrent Glioblastomas

NCT07620548 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 26-x027
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 2

Brief Summary

This study will assess the therapeutic efficacy of the combination of Laser Interstitial Thermal Therapy (LiTT) with adjuvant cemiplimab compared to the therapeutic efficacy of the combination of LiTT with physician's choice of adjuvant chemotherapy in patients with recurrent glioblastoma. Patients will be enrolled and randomized on a 2:1 ratio to either the experimental arm (LiTT + cemiplimab) or the control arm (LiTT + physician/s choice chemotherapy).

Conditions

Glioblastoma; Glioblastoma, IDH-wildtype; Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype

Keywords

GBM; Recurrent; IDH-wt; IDH-wildtype; Glioblastoma; Immunotherapy; LiTT

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (PFS) at Month 6 (PFS6)

  PFS6 as defined from the time of treatment start to the time of progression (based on clinical assessment and imaging per Immunotherapy Response Assessment in Neuro-Oncology (iRANO)) or death, whichever is earlier, or last follow-up if neither progression nor death event is observed. PFS6 will be estimated as the empirical PFS probability at Month 6 using the Kaplan-Meier method.

  Start of treatment through 6 months after start of treatment (month 6)

• Overall survival (OS) at Month 18 (OS18)

  OS as defined from the time of treatment start to the time of death or last follow up if surviving; OS-18 is further estimated as the empirical OS probability at Month 18 using the Kaplan-Meier method.

  Start of treatment through 18 months after start of treatment (month 18)

Secondary Outcomes (8)

• Median Progression-Free Survival (PFS) as determined using the Kaplan-Meier method

  Start of treatment through 1 year after completion of treatment or progression (up to 3 years)

• Median Overall Survival (OS) as determined using the Kaplan-Meier method

  Start of treatment through 1 year after completion of treatment or progression (up to 3 years)

• Objective Response Rate (ORR)

  Start of treatment through completion of treatment or progression (up to 2 years)

• Disease control rate (DCR)

  Start of treatment through 1 year after completion of treatment or progression (up to 3 years)

• Duration of response (DoR)

  From first positive response (6 weeks after start of treatment) through 1 year after completion of treatment or progression (up to 3 years)

Study Arms (2)

Experimental Arm: LiTT + Cemiplimab

EXPERIMENTAL

Patients in the Experimental Arm will receive adjuvant cemiplimab (at a dose of 350 mg intravenously (IV)) every 3 weeks after LiTT for a maximum total of 36 months (or until disease progression or intolerable adverse event). The first adjuvant dose of cemiplimab must be given within 14 days post-LiTT.

Device: NeuroBlate® Laser Ablation Laser Interstitial Thermal Therapy; Drug: Cemiplimab

Control Arm: LiTT + adjuvant chemotherapy

ACTIVE COMPARATOR

Patients in the Control Arm will undergo LiTT, then will receive adjuvant chemotherapy (chosen by their treating physician) for up to 12 months as per standard of care (SOC), starting within 14 days post-LiTT.

Device: NeuroBlate® Laser Ablation Laser Interstitial Thermal Therapy; Drug: Chemotherapy

Interventions

NeuroBlate® Laser Ablation Laser Interstitial Thermal Therapy DEVICE

LiTT, or magnetic resource imaging (MRI)-guided laser ablation, is a minimally invasive surgery approved for cytoreductive treatment of brain tumors. It employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MRI imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim.

Also known as: LiTT

Control Arm: LiTT + adjuvant chemotherapy; Experimental Arm: LiTT + Cemiplimab

Cemiplimab DRUG

Cemiplimab is a programmed death receptor-1 (PD-1)-blocking antibody that is administered intravenously at 350mg over 30 minutes every 3 weeks on an outpatient basis.

Also known as: Libtayo®

Experimental Arm: LiTT + Cemiplimab

Chemotherapy DRUG

Adjuvant chemotherapy will be decided by the physician's choice of best fit by patient, including the agent(s), dosing, and schedule.

Control Arm: LiTT + adjuvant chemotherapy

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed WHO grade 4 GBM (IDH-wt). Note: GBM variants, including histone-mutant and molecular-defined gliomas per WHO 2021 are allowed. Any number of recurrences are permitted.
• Unequivocal evidence of tumor progression as documented on the screening biopsy.
• At least 12 weeks post-completion of standard frontline therapy. Standard frontline therapy in this population includes maximal feasible surgical resection (biopsy alone is allowed), radiotherapy, and temozolomide chemotherapy. There is no restriction on the number of adjuvant temozolomide cycles.
• Candidate for LITT based on the size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon. Surgical resection/debulking prior to LITT is allowed per standard of care but is not required; if the patient undergoes resection or debulking, it must have occurred at least 3 weeks prior to the start of any study treatment.
• At least 18 years of age.
• Karnofsky performance status ≥ 60%
• Adequate bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1.5 K/cumm
• Platelets ≥ 100 K/cumm
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
• Creatinine clearance \> 30 mL/min by Cockcroft-Gault
• INR or PT ≤ 1.5 x IULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
• aPTT ≤ 1.5 x IULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants)

You may not qualify if:

• Received prior treatment with any anti-angiogenic agent (including bevacizumab) within 3 months of date of surgery (LITT). (Note: bevacizumab is otherwise permitted when used outside this window for cerebral edema.)
• Received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD127, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Received prior treatment with a monoclonal antibody within 4 weeks prior to the first day of study treatment.
• Received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first day of study treatment.
• Has not recovered (i.e., grade 1 or baseline) from adverse events caused by anti-cancer agents administered no more than 4 weeks prior to consent. Note: patients with ≤ grade 2 neuropathy are an exception to this criterion. Note: if a patient underwent major surgery, they must have recovered adequately from the toxicity and/or complications prior to the first day of study treatment.
• Candidate for curative resection or urgent surgical procedure(s) needed.
• Presence of brainstem lesions or lesions that are \< 5 mm from the hypophysis or cranial nerves.
• Multifocal glioma that is bilateral. Patients with unilateral multifocal gliomas may be eligible if their multifocal disease can be treated effectively and safely in a single LITT procedure. Note: Corpus callosal tumors are eligible even if they are bilateral as long as they satisfy the size and shape limits of LITT as determined by the performing neurosurgeon.
• Presence of leptomeningeal metastases.
• Recent (within 8 weeks) history of CNS hemorrhage unless the hemorrhage is located within the tumor that will be removed en total during surgical debulking or ablated during LITT.
• Requires therapeutic doses of anticoagulants unless anticoagulation can be safely discontinued before surgery per standard practice or an IVC filter can be used in place of anticoagulation. Patients are permitted to resume anticoagulation following LITT at the discretion of their treating physician.
• Received prior local therapy (stereotactic radiosurgery, brachytherapy, or carmustine wafers) to the proposed area of LITT.
• Received a live vaccine or live-attenuated vaccine within 28 days prior to the first day of study treatment. Received COVID-19 vaccine within 7 days of first dose.
• Currently receiving any other investigational agents or has participated in a study of an investigational agent or device within 3 weeks of the first day of study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents used in the study.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Glioblastoma; Recurrence

Interventions

cemiplimab; Drug Therapy

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Omar H Butt, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Omar H Butt, M.D., Ph.D.

CONTACT

215-279-3388; omarhbutt@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2026
• First Posted: June 2, 2026
• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): August 31, 2032
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months and ending 5 years following study article publication
• Access Criteria: Researchers who provide a methodologically sound proposal. If approved, a data access/transfer agreement to be completed. Proposal requests to be emailed to corresponding article author. Link will be included on study conclusion

Locations

US (2)