CUE-102 in Recurrent Glioblastoma

NCT06917885 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-023
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this study is to evaluate the safety of the experimental drug, CUE-102, and establish the recommended dose of CUE-102 for participants with Recurrent Glioblastoma (GBM). The name of the study drug involved in this study is:

• CUE-102 (a type of fusion protein)

Conditions

Recurrent Glioblastoma; Glioblastoma; Glioma, Malignant

Keywords

Glioblastoma; Recurrent Glioblastoma; Glioma, Malignant

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Dose-limiting-toxicities (DLT)

  A DLT is defined as any adverse event (AE) considered related to CUE-102 that meets DLT criteria in the 21-day period following the first dose of CUE-102 including pre-treatment laboratory results required for C2D1.

  3 weeks

• Maximum Tolerated Dose (MTD)

  MTD is determined using a 3+3 design as listed in protocol section 1.1

  3 weeks

Secondary Outcomes (1)

• Safety and tolerability

  Up to 1 year

Study Arms (1)

CUE-102

EXPERIMENTAL

The first 12 participants will be enrolled using a standard 3 + 3 design in a safety lead-in to determine the maximum tolerated dose (MTD) of CUE-102 per protocol. Once the MTD has been determined, up to 6 additional participants will be enrolled in a dose expansion cohort. Participants will complete: * Baseline visit * Imaging every 9 weeks starting at Cycle 3 * Cycle 1 through End of Treatment (up to 1 year in total, approximately 17 cycles) --Day 1 of 21 day cycle: Predetermined dose of CUE-102 1x daily. * End of Treatment visit with imaging * Long-Term Follow Up: every 3-4 months

Biological: CUE-102

Interventions

CUE-102 BIOLOGICAL

A WT-1-pHLA-IL2-Fc fusion protein, single-use vial, via intravenous (into the vein) infusion per protocol.

CUE-102

Eligibility Criteria

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

You may qualify if:

• Have HLA-A\*0201 genotype as determined by genomic testing performed locally;
• Have histologically confirmed World Health Organization (WHO) Grade 4 glioblastoma, other WHO grade 4 malignant glioma or molecular GBM (based on the 2021 WHO Classification) at first recurrence. Patients with gliosarcoma are NOT eligible;
• Be willing and able to provide written informed consent/assent for the trial;
• Be ≥ 18 years of age on day of signing informed consent;
• Have a Karnofsky performance status (KPS) ≥ 70 (Appendix A);
• Participants must be at least 4 weeks from start of last chemotherapy cycle (at least 6 weeks for nitrosoureas and at least 1 week for metronomic dosing) and at least 4 weeks or 5 half-lives (whichever is shorter) for any prior investigational agent. There is no minimal time from cessation of Optune TTF nor for prior cancer vaccine therapy.
• MRI within 14 days prior to registration. MRIs should include vascular imaging when possible. Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan. If steroids are added or the steroid dose is increased between the date of the screening MRI scan and the start of treatment, a new baseline MRI or CT is required;
• Patients must have fully completed initial radiation therapy with or without daily temozolomide including 60 Gy in 30 fractions, 59.4 Gy in 1.8 Gy per fraction or equivalent;
• At least 12 weeks from completion of radiotherapy +/- temozolomide. Patients \< 12 weeks from the completion of radiation therapy may be eligible if they have either of the following: 1) histopathologic confirmation of recurrent tumor; or 2) new contrast enhancing disease outside the primary radiation field. Participants who have received investigational therapies as a component of treatment for newly diagnosed GBM as long as remaining eligibility criteria are satisfied;
• Participants must meet the following organ and marrow function as defined below, all screening labs should be performed within 14 days of registration:
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks)
• Serum creatinine ≤ 1.5 X institutional ULN OR
• Measured or calculated creatinine clearance (CrCl) ≥45 mL/min for participant with creatinine levels \> 1.5 X institutional ULN (CrCl should be calculated per institutional standard, GFR can also be used in place of creatinine or CrCl)

You may not qualify if:

• Received any therapy for tumor recurrence other than surgery;
• More than one episode of recurrent or progressive tumor;
• Is currently participating or plans to participate in another study of an investigational agent or using an investigational device.
• Tumor primarily localized to the brainstem or spinal cord;
• Presence of multifocal tumor, bi-hemispheric tumor (radiographic evidence of tumor extending from one hemisphere into the other through the corpus callosum), diffuse leptomeningeal or extracranial disease;
• Has a diagnosis of immunodeficiency;
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. Examples include - but are not limited to - unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements;
• Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of enrollment;
• Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans;
• Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade \> 3 within 6 months of enrollment;
• Has a known additional malignancy that is progressing or requires active treatment within 1 year of start of study drug, except for those treated with surgical therapy only (e.g. basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy);
• Has active autoimmune disease requiring 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 for adrenal insufficiency or pituitary/hypothalamic dysfunction, etc.) is not considered a form of systemic treatment;
• Has history of (non-infectious) pneumonitis that required steroids or has current pneumonitis;
• Has an active infection requiring systemic therapy within 7 days before enrollment;
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial;

Sponsors & Collaborators

• David Reardon, MD: lead
• Cue Biopharma: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Glioma

Condition Hierarchy (Ancestors)

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

Study Officials

• David Reardon, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Reardon, MD

CONTACT

617-632-4750; david_reardon@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 9, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)