Study of ABBV-637 or ABBV-155 With ERAS-801 for People With Glioblastoma

NCT06934889 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 24-409
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 10

Brief Summary

The researchers are doing this study to find out whether the drugs ABBV-637 and ABBV-155 are safe treatments that cause few or mild side effects when given alone or in combination with ERAS-801 in people with recurrent GBM.

Conditions

Glioblastoma; Gliosarcoma

Keywords

WHO grade IV; ABBV-637; ABBV-155; ERAS-801; 24-409

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  All patients who receive a single dose of investigational drug will be included in the primary endpoint analysis. Will be measured descriptively using CTCAE v5.0

  1 year

Secondary Outcomes (2)

• Overall survival

  1 year

• Progression-free survival (PFS)

  6 months

Study Arms (4)

Cohort A (Recurrent)

EXPERIMENTAL

will receive ABBV-637 before standard surgery, followed by ABBV-637 and ERAS-801 after standard surgery.

Drug: ERAS-801; Drug: ABBV-637

Cohort B (Recurrent)

EXPERIMENTAL

will receive ABBV-155 before standard surgery, followed by ABBV-155 and ERAS-801 after standard surgery

Drug: ERAS-801; Drug: ABBV-155

Cohort C (Newly Diagnosed)

EXPERIMENTAL

will receive ABBV-637 in combination with standard radiation and chemotherapy drug temozolomide.

Drug: ABBV-637; Drug: Temozolomide; Radiation: Radiotherapy

Cohort D (Newly Diagnosed)

EXPERIMENTAL

will receive ABBV-155 in combination with standard radiation and chemotherapy drug temozolomide

Drug: ABBV-155; Drug: Temozolomide; Radiation: Radiotherapy

Interventions

ERAS-801 DRUG

will be administered orally at the assigned dose once daily starting on Cycle 1 Day 1.

Cohort A (Recurrent); Cohort B (Recurrent)

ABBV-637 DRUG

will be administered intravenously over one hour (+/- 10 min) once every 28 days on the first day of the new cycle.

Cohort A (Recurrent); Cohort C (Newly Diagnosed)

ABBV-155 DRUG

will be administered intravenously over at least 30 minutes once every 21 days on the first day of the new cycle.

Cohort B (Recurrent); Cohort D (Newly Diagnosed)

Temozolomide DRUG

Temozolomide will be continued for 6 cycles after radiation.

Cohort C (Newly Diagnosed); Cohort D (Newly Diagnosed)

Radiotherapy RADIATION

will be given as per standard of care radiation for GBM

Cohort C (Newly Diagnosed); Cohort D (Newly Diagnosed)

Eligibility Criteria

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

You may qualify if:

• Patients must be 18 years of age or older at the time of consent signing.
• All Patients must have WHO Grade IV Glioblastoma/Gliosarcoma using WHO 2021 criteria and include the diagnosis of molecular GBM, recurrent patients must be progressive or recurrent following radiation therapy +/- chemotherapy
• Patients must be IDH wild type by CLIA-certified laboratory assay available at time of consent.
• Patients must have evidence of EGFR gene amplification by CLIA-certified laboratory assay at time of consent.
• Patients must have measurable disease as per RANO criteria pre-operatively (there is no requirement for post-operative disease to be present or absent). \[cohort A/B only\]
• Patients must be able to tolerate MRIs
• Patients may have no more than 2 prior therapy regimens. \[cohort A/B only\]
• Patients must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:
• weeks from the completion of radiation
• weeks from a nitrosourea chemotherapy
• weeks from a non-nitrosourea chemotherapy
• weeks from any investigational (not FDA-approved) agents
• months from the last treatment with bevacizumab
• weeks or 5 half-lives from administration of a non-cytotoxic, Chemotherapies other than bevacizumab, whichever is shorter
• Patients must be undergoing surgery that is clinically indicated as determined by their care providers. \[cohort A/B only\] Patients must be eligible for surgical resection according to the following criteria:

You may not qualify if:

• Patients may not be receiving any other investigational agents.
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the investigational agents are ineligible.
• Patients with prior therapy with EGFR targeting agents are ineligible because treatment with EGFR kinase inhibitors or other EGFR-targeted agents has the potential to deplete the tumor of EGFR-amplified or EGFR mutant cell populations and confound the evaluation of the investigational regimen. Patients would only be eligible if surgery on a recurrence after the EGFR-targeted therapy confirmed persistence of an EGFR alteration.
• Patients on enzyme-inducing anti-epileptic drugs (EIAED) are not eligible for treatment on this protocol. Patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs. Patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of study drug(s).
• Patients must not have evidence of significant hematologic, renal, or hepatic dysfunctioPatients must not have evidence of significant intracranial hemorrhage (For example, in the recurrent setting, circumstances where the intracranial hemorrhage would obscure the amount and quality of tissue obtained at the time of the on-treatment surgery).
• Patients with uncontrolled intercurrent illness including, but not limited to, hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements, are ineligible.
• Participants with clinically significant cardiovascular disease including, but not limited to:
• No recent history (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, cardiac arrhythmia requiring pharmacological or surgical intervention, pericardial effusion, or pericarditis.
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG, e.g., complete left bundle branch block, second- or third-degree heart block, PR-interval \> 250 ms.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, or any concomitant medication know to prolong the QT interval.
• No history of clinically significant medical and/or psychiatric conditions or any other reason that, in the opinion of the investigator, would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug
• Pregnant women are excluded from this study because the investigational regimens have potential for teratogenic or abortifacients effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated on this study.
• HIV-positive patients on strong CYP3A4 inducers or inhibitors are ineligible because of the potential for pharmacokinetic interactions.
• Patients who have acute or currently active/requiring anti-viral therapy hepatic or biliary disease are ineligible (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases from the primary brain tumor, or stable chronic liver disease per investigator assessment).
• Patients receiving P-gp inhibitors/P-gp substrates with narrow therapeutic index are ineligible.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (10)

University of Miami (Data collection only)

Miami, Florida, 33136, United States

RECRUITING

Indiana University (Data Collection Only)

Indianapolis, Indiana, 46202, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Rockville Centre, New York, 11553, United States

RECRUITING

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

NOT YET RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Temozolomide; Radiotherapy

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Thomas Kaley, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Kaley, MD

CONTACT

212-639-5122; kaleyt@mskcc.org

Ingo Mellinghoff, MD

CONTACT

646-888-2766

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase Ib Trial of ABBV-637 or ABBV-155 in Combination with ERAS-801. The first eight patients were randomized 1:1 to: ABBV-637 or ABBV-155 (6 to cohorts A/B and 2 to cohorts C/D) using the Randomization Module in the Clinical Research Database (CRDB). Due to drug viability and impending expiration dates, the trial will no longer use randomization going forward beginning with patient 9. Participants will be assigned.

Study Record Dates

• First Submitted: April 11, 2025
• First Posted: April 18, 2025
• Study Start: April 7, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (10)