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

A Randomized Phase II Study of the Efficacy of Laser Interstitial Thermal Therapy (LiTT) Combined With Cemiplimab Versus Physician's Choice Chemotherapy in Recurrent Glioblastomas

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma; Glioblastoma, IDH-wildtype; Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype
• Intervention / Treatment: Device: NeuroBlate® Laser Ablation Laser Interstitial Thermal Therapy; Drug: Cemiplimab; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 99
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Omar H Butt, M.D., Ph.D.; Phone Number: 215-279-3388; Email: omarhbutt@wustl.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
      • Contact: Jian L Campian, M.D., Ph.D.; Phone Number: 507-512-8186; Email: campian.jian@mayo.edu
      • Principal Investigator: Jian L Campian, M.D., Ph.D.
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
      • Sub-Investigator: Milan Chheda, M.D.
      • Sub-Investigator: Eric Leuthardt, M.D.
      • Sub-Investigator: Tanner M Johanns, M.D., Ph.D.
      • Sub-Investigator: Jingqin (Rosy) Luo, Ph.D.
      • Sub-Investigator: Dimitrios Mathios, M.D.
      • Principal Investigator: Omar H Butt, M.D., Ph.D.
      • Sub-Investigator: Albert H Kim, M.D., Ph.D.
      • Contact: Omar H Butt, M.D., Ph.D.; Phone Number: 215-279-3388; Email: omarhbutt@wustl.edu
      • Sub-Investigator: Yu (Jade) Tao, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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)
• The effects of cemiplimab on the developing human fetus are unknown. For this reason, people of childbearing potential and people able to father a child must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after completion of study participation (for patients in the Experimental Arm) OR 14 days after completion of study participation (for people of childbearing potential in the Control Arm) or 4 months (for people able to father a child in the Control Arm).
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

• 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.
• Dexamethasone > 4 mg at the time of consent.
• 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 trial treatment (with the exception of daily dexamethasone ≤ 4 mg).
• History of immune related pneumonitis or (non-infectious) interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease in the last 5 years.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection or infection requiring hospitalization or treatment with IV anti-infectives within 14 days of first dose, myocardial infarction within 12 months of first dose, symptomatic congestive heart failure, unstable angina pectoris, acute coronary syndrome within 12 months of first dose, transient ischemic attack or stroke within 12 months of first dose, or cardiac arrhythmia. New York Heart Association Function Classification of class II, II, or IV are exclusionary.
• Has an active autoimmune disease requiring systemic treatment within 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.
• Pregnant and/or breastfeeding. People of childbearing potential must have a negative pregnancy test within 14 days of study entry and again within 72 hours of initiation of cemiplimab (if applicable).
• Active or latent tuberculosis.
• History of HIV infection if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
• Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
• History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm: LiTT + Cemiplimab; 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; 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.; Other Names: LiTT; Drug: Cemiplimab; 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.; Other Names: Libtayo®
Active Comparator: Control Arm: LiTT + adjuvant chemotherapy; 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; 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.; Other Names: LiTT; Drug: Chemotherapy; Adjuvant chemotherapy will be decided by the physician's choice of best fit by patient, including the agent(s), dosing, and schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Progression-Free Survival (PFS) as determined using the Kaplan-Meier method	PFS 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.	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	OS as defined from the time of treatment start to the time of death or last follow up if surviving.	Start of treatment through 1 year after completion of treatment or progression (up to 3 years)
Objective Response Rate (ORR)	Proportion of patients achieving Complete Response (CR) or Partial Response (PR) by iRANO criteria. CR - Requires all of the following: complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks. No new lesions; stable or improved non-enhancing (T2/FLAIR) lesions. Patients must be off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically. PR - Requires all of the following: ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. No progression of nonmeasurable disease. Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. Stable or improved clinically.	Start of treatment through completion of treatment or progression (up to 2 years)
Disease control rate (DCR)	DCR, defined as proportion of patients achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) by iRANO criteria.	Start of treatment through 1 year after completion of treatment or progression (up to 3 years)
Duration of response (DoR)	DoR, defined as the time period from when a patient first achieves a positive response (complete or partial response) by iRANO criteria to when disease progresses or death.	From first positive response (6 weeks after start of treatment) through 1 year after completion of treatment or progression (up to 3 years)
Number of participants with adverse events as defined by CTCAE v5.0		Start of treatment through 90 days after last dose of treatment (up to 27 months)
Changes in Health-related quality of life (HRQoL) as measured by the EORTC QLQ C30	HRQoL changes over the timeline of the trial will be assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) questionnaire which examines 5 major domains (physical, role, emotional, social, cognitive). The questionnaire is composed of 30 questions. Twenty-eight questions follow a 4-point scale ranked as follows: 1 Not at all, 2 A Little, 3 Quite a bit, and 4 Very much. Two questions follow a 7-point Likert scale from 1 Very Poor to 7 Excellent. The higher the score, the higher quality of life.	Baseline through end of treatment (up to 3 years)
Changes in neurologic symptoms as measured by the EORTC QLQ BN20	Changes in patient's neurologic symptoms across the timeline of the trial will be assessed via the EORTC QLQ BN20 questionnaire, which is specifically formulated to assess symptoms and quality of life of brain cancer patients. The questionnaire is composed of 20 questions that follow a 4-point scale ranked as follows: 1 Not at all, 2 A Little, 3 Quite a bit, and 4 Very much. Separate symptom and quality of life scores are calculated according to the validated measure. The higher the score on the symptom scale generally means a greater severity of symptoms and a higher score on the functionality scale generally means a higher quality of life.	Baseline through end of treatment (up to 2 years)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Omar H Butt, M.D., Ph.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): August 31, 2032

Study Registration Dates

• First Submitted: May 26, 2026
• First Submitted That Met QC Criteria: May 26, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: GBM; Immunotherapy; Glioblastoma; Recurrent; IDH-wildtype; IDH-wt; LiTT
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pathological Conditions, Signs and Symptoms; Recurrence; Glioblastoma; Therapeutics; Drug Therapy; cemiplimab
• Other Study ID Numbers: 26-x027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlies the results reported will be shared (after deidentification) at time of final reporting/article. This will further include study protocol and statistical plan.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following study article publication
• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes