Abemaciclib + Pembrolizumab In Glioblastoma

NCT04118036 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 19-351
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a combination therapy as a possible treatment for recurrent glioblastoma (GBM), a brain tumor that is growing or progressing despite earlier treatment. This study will involve participants with recurrent glioblastoma at their first relapse enrolled in two arms including patients who require reoperation and patients not requiring surgery. This research study involves a combination of two drugs:

• Pembrolizumab (MK3475)
• Abemaciclib (LY2835219)

Conditions

Glioblastoma

Keywords

Glioblastoma

Outcome Measures

Primary Outcomes (7)

• TIL density in tumor tissue (surgery)

  One-sided Wilcoxon test

  Day 1-Post Surgery

• Progression Free Survival 6 months (non surgery)

  Kaplan Meier curves

  6 months

• Radiographic response rate (non surgery)

  RANO Criteria

  2 years

• Median progression free survival

  2 Years

• Overall survival

  calculated using standard statistical methods

  From date of first dose (date of first post-surgery treatment for participants in Cohort 1) to date of death due to any causeup to 100 months

• Tumor cell death (Surgery)

  Effects of abemaciclib and pembrolizumab on tumor cell proliferation and tumor cell death will be measured using immunohistochemistry for pRB1, Ki-67 and Cleaved Caspase 3

  2 years

• tumor cell proliferation (surgery)

  Effects of abemaciclib and pembrolizumab on tumor cell proliferation and tumor cell death will be measured using immunohistochemistry for pRB1, Ki-67 and Cleaved Caspase 3

  2 years

Study Arms (2)

Surgery Arm

EXPERIMENTAL

In the surgical arm participants who require reoperation and have evidence of CDKN2A/B or C loss and intact RB from a prior tumor sample will receive * Pembrolizumab-prior to surgery, at predetermined dose and time point * Abemaciclib: every 12 hours from the day of pembrolizumab infusion to the morning of surgery * Post surgery Participants with receive * Abemaciclib, twice daily oral at specified dose for 21 day cycle * Pembrolizumab intravenous once in 21 day cycle (3 weeks)

Drug: Pembrolizumab; Drug: Abemaciclib

Non Surgery Arm

EXPERIMENTAL

The treatment arm will be comprised of participants not requiring surgery. \- Participants will receive treatment with * Abemaciclib, twice daily oral at specified dose for 21 day cycle * Pembrolizumab intravenous once in 21 day cycle (3 weeks)

Drug: Pembrolizumab; Drug: Abemaciclib

Interventions

Pembrolizumab DRUG

intravenously over 30 minutes every 21 days (+/- 3 days)

Also known as: Keytruda

Non Surgery Arm; Surgery Arm

Abemaciclib DRUG

Oral 2 times a day

Also known as: Verzenio

Non Surgery Arm; Surgery Arm

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Participants must be able to understand and willing to sign a written informed consent document.
• Participants must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary.
• Participants must be at least 18 years old on day of signing informed consent.
• Participants must have a Karnofsky Performance Status (KPS) ≥ 70 (see Appendix A).
• Participants must be able to swallow oral medications.
• Nature of illness and treatment history
• Participants must have histologically confirmed diagnosis of glioblastoma or variants. Participants will not be eligible if the prior diagnosis was low-grade glioma and a subsequent histological diagnosis of glioblastoma or variants was made (e.g. secondary GBM).
• To be eligible for the study all participants (Cohort 1 and 2) are required to provide genomic profiling data from a sequencing-based assay and must include reporting of the RB1 gene in explicit terms within the report. Only sequencing assays that include coverage of all exons of the RB1 gene are able to be utilized (most commonly called a targeted exome assay; e.g. Oncopanel, Impact, FoundationOne). In addition, patients must provide a report of copy assessment which reports status of RB1. The reporting may be from a copy array (ideally Oncoscan SNP array or Agilent array CGH) or can also be from sequencing assay if copy status is explicitly provided with quantitative information regarding the status of relevant genes.
• Inactivation of CDKN2A/B or C in the tumor by homozygous deletion (evidence for more than single copy loss for any of the genes defined as copy array log2 ratio of \<0.3 by copy array; or from sequencing data with sufficient coverage for evaluation). Rearrangement/evidence or intragenic breaks by copy or sequencing assay also will be considered eligible for study (any copy status).
• Validation of wild-type RB status (no deletion/losses more than single copy by copy number or sequencing data; and/or no inactivating mutations or rearrangement by sequencing).
• Participants must be at first relapse of GBM. Relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy). The intent therefore is that patients had no more than 1 prior therapy (initial treatment). If the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered to constitute 1 relapse.
• Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.
• For Cohort 2 subjects, CT or MRI within 14 days prior to study registration. For Cohort 2, 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 or CT scan and the start of treatment, a new baseline MRI or CT is required.
• For Cohort 1 subjects, CT or MRI should be performed ideally within 14 days prior to study registration, but because the screening MRI for this subset of subjects will not be used for evaluation of response, it is acceptable for this MRI/CT to have been performed greater than 14 days prior to registration if unavoidable. Furthermore, for this same reason, fluctuation in corticosteroid dose around this MRI does not warrant repeat scan so long as there is documented unequivocal evidence of tumor progression available.

You may not qualify if:

• Participants who meet any of the following criteria will not be eligible for admission into the study.
• Pathology
• Prior evidence of 1p/19q co-deletion.
• IDH1/2 mutation in any prior biopsy.
• Tumor primarily localized to the brainstem or spinal cord.
• Presence of diffuse leptomeningeal disease or extracranial disease.
• Previous therapies
• Participants who have received prior treatment with a CDK4/6 inhibitor (e.g. abemaciclib, palbociclib).
• Participants who have received anti-VEGF targeted agents (e.g. bevacizumab, cediranib, aflibercept, vandetanib, XL184, sunitinib etc.).
• Participants who have received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Participants who have received prior interstitial brachytherapy, implanted chemotherapy, stereotactic radiosurgery or therapeutics delivered by local injection (including intra-tumoral vaccines) or convection enhanced delivery.
• Concomitant medications
• Participants requiring treatment with high dose systemic corticosteroids defined as dexamethasone \> 2 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of start of study drug.
• Participants who have received systemic immunosuppressive treatments, aside from systemic corticosteroids (such as methotrexate, chloroquine, azathioprine, etc.) within six months of start of study drug.
• Participants taking an enzyme-inducing anti-epileptic drug (EIAED): phenobarbital, phenytoin, fosphenytoin, primidone, carbamazepine, oxcarbazepine, eslicarbazepine, rufinamide, and felbamate. Participants must be off any EIAEDs for at least 14 days prior to starting study drug. A list of EIAEDs and other inducers of CYP3A4 can be found in Appendix D.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

pembrolizumab; abemaciclib

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

Study Officials

• Patrick Wen, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 4, 2019
• First Posted: October 7, 2019
• Study Start: December 1, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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)