The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive Enhancing IDH-1 Mutant Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05484622
Recruitment Status : Recruiting
First Posted : August 2, 2022
Last Update Posted : May 8, 2024
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

Tracking Information
First Submitted Date  ICMJE July 21, 2022
First Posted Date  ICMJE August 2, 2022
Last Update Posted Date May 8, 2024
Actual Study Start Date  ICMJE January 20, 2023
Estimated Primary Completion Date February 28, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2022)
  • Safety Lead-in Phase: Percentage of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: First 21 days of dosing (Cycle 1) in safety lead-in phase ]
  • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: approximately up to 19 months ]
  • Percentage of Tumor-infiltrating Lymphocyte (TIL) Cells in Surgically Resected Tumors Following Treatment With Vorasidenib + Pembrolizumab Compared to Untreated Control Tumors [ Time Frame: approximately 2 months ]
    TIL is defined as the percentage of tumor-infiltrating lymphocyte cells on a logarithmic scale.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2024)
  • Overall Survival (OS) [ Time Frame: Up to approximately 55 months ]
    Overall survival is defined as the time from the date of first dose (in Safety Lead-in) or first postoperative dose (in randomized perioperative phase) to the date of death due to any cause.
  • AUC: Area Under the Plasma Concentration-Time Curve of Vorasidenib [ Time Frame: approximately 16 months ]
  • Cmax: Maximum Observed Plasma Concentration of Vorasidenib [ Time Frame: approximately 16 months ]
  • Concentration of 2-hydroxygluarate (2-HG) in Surgically Resected Tumors [ Time Frame: approximately 2 months ]
  • Concentration of Vorasidenib in Surgically Resected Tumors [ Time Frame: approximately 2 months ]
  • Clinical Activity Associated With Vorasidenib in Combination With Pembrolizumab According to Modified Response Assessment in Neuro-oncology (mRANO) Criteria [ Time Frame: Up to approximately 16 months ]
  • Time to response [ Time Frame: Up to approximately 55 months ]
    Defined as the time from the date of first dose (in Safety Lead-In) or the date of first postoperative dose (in randomized perioperative phase) to the date of first documented objective response as assessed by the Investigator per Modified Response Assessment in Neuro-oncology (mRANO) criteria.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2022)
  • Overall Survival (OS) [ Time Frame: Up to approximately 55 months ]
    Overall survival is defined as the time from the date of first dose (in Safety Lead-in) or first postoperative dose (in randomized perioperative phase) to the date of death due to any cause.
  • AUC: Area Under the Plasma Concentration-Time Curve of Vorasidenib [ Time Frame: approximately 16 months ]
  • Cmax: Maximum Observed Plasma Concentration of Vorasidenib [ Time Frame: approximately 16 months ]
  • Concentration of 2-hydroxygluarate (2-HG) in Surgically Resected Tumors [ Time Frame: approximately 2 months ]
  • Concentration of Vorasidenib in Surgically Resected Tumors [ Time Frame: approximately 2 months ]
  • Clinical Activity Associated With Vorasidenib in Combination With Pembrolizumab According to Modified Response Assessment in Neuro-oncology (mRANO) Criteria [ Time Frame: Up to approximately 16 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive Enhancing IDH-1 Mutant Glioma
Official Title  ICMJE A Phase 1, Safety Lead-In and Randomized, Open-label, Perioperative Study of Vorasidenib in Combination With Pembrolizumab in Subjects With Recurrent or Progressive Enhancing IDH-1 Mutant Glioma
Brief Summary Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive enhancing isocitrate dehydrogenase-1 (IDH-1) mutant Glioma.
Detailed Description

The study is divided into 2 phases, a Safety Lead-In phase and a randomized perioperative phase. In the Safety Lead-In Phase, the recommended combination dose (RCD) of vorasidenib will be determined. In the Randomized Perioperative Phase, the Lymphocytes infiltration in tumors will be evaluated following pre-surgical treatment with vorasidenib and pembrolizumab combination, compared to untreated control tumors. Prior to surgery, participants will be randomized to receive vorasidenib at the RCD in combination with pembrolizumab, or vorasidenib only, or no treatment (untreated control group). Following surgery, participants will have the option to receive treatment with vorasidenib in combination with pembrolizumab in 21-day cycles.

Study treatment will be administered until participant experiences unacceptable toxicity, disease progression, or other discontinuation criteria are met.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Sequential design for safety lead-in and randomized perioperative phases, parallel design within randomized perioperative phase.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Astrocytoma
Intervention  ICMJE
  • Drug: Vorasidenib
    Administered orally as tablets.
    Other Names:
    • S095032
    • AG-881
  • Drug: Pembrolizumab
    Administered as IV infusion.
    Other Names:
    • MK-3475
    • KEYTRUDA®
    • KEYNOTE-B39
    • MK-3475-B39
Study Arms  ICMJE
  • Experimental: Safety Lead-In Phase: Vorasidenib + Pembrolizumab
    Participants will receive vorasidenib orally, once daily (QD) in combination with pembrolizumab 200 mg intravenous (IV) infusion, once every 3 weeks (Q3W) in each 21-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
    Interventions:
    • Drug: Vorasidenib
    • Drug: Pembrolizumab
  • Experimental: Randomized Perioperative Phase: Vorasidenib + Pembrolizumab
    Participants will receive vorasidenib recommended combination dose (RCD) determined in the Safety Lead-in phase, orally, QD from Day 1 to 28 in combination with pembrolizumab 200 mg IV infusion, Q3W on Days 1 and 22 of a 28-day cycle prior to surgery.
    Interventions:
    • Drug: Vorasidenib
    • Drug: Pembrolizumab
  • Experimental: Randomized Perioperative Phase: Vorasidenib Only
    Participants will receive vorasidenib orally, QD from Day 1 to 28 of a 28-day cycle prior to surgery.
    Intervention: Drug: Vorasidenib
  • No Intervention: Randomized Perioperative Phase: Untreated Control Group
    Participants will not receive any treatment prior to surgery.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 1, 2022)		 72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 30, 2027
Estimated Primary Completion Date February 28, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Have Karnofsky Performance Status (KPS) of ≥ 70%.
  2. Have expected survival of ≥ 3 months.
  3. Have histologically confirmed Grade 2 or Grade 3 astrocytoma (per the 2016 or 2021 World Health Organization [WHO] Classification of Tumors of the central nervous system)
  4. Have documented IDH1-R132H gene mutation and for Astrocytomas: Absence of 1p19q co-deletion (i.e., exclusion of combined whole-arm deletions of 1p and 19q) and/or documented loss of nuclear ATRX expression or ATRX mutation by local testing. For Oligodendrogliomas: Presence of 1p19q co-deletion (i.e., combined whole-arm deletions of 1p and 19q) by local testing.
  5. Have measurable, magnetic resonance imaging (MRI)-evaluable, unequivocal contrast enhancing disease as determined by institution radiologist/Investigator at Screening on either 2D T1 post-contrast weighted images or 3D T1 post-contrast weighted images. Per mRANO criteria, measurable lesion is defined as at least 1 enhancing lesion measuring ≥ 1 cm x ≥ 1 cm.
  6. Have recurrent or progressive disease and received prior treatment with chemotherapy, radiation, or both.
  7. Surgical resection is indicated for treatment, but surgery is not urgently indicated (e.g., for whom surgery within the next 6-9 weeks is appropriate). (NOTE: This criterion only applies to participants enrolled in the perioperative phase of the study. Participants in the Safety Lead-In should not require surgery).

Exclusion Criteria:

  1. Have received prior systemic anti-cancer therapy within 1 month of the first dose of IMP, radiation within 12 months of the first dose of IMP, or an investigational agent < 14 days prior to the first dose of IMP. In addition, the first dose of IMP should not occur before a period of ≥ 5 half-lives of the investigational agent has elapsed.
  2. Have received 2 or more courses of radiation.
  3. Have received any prior treatment with an isocitrate dehydrogenase (IDH) inhibitor; anti-programmed cell death 1 (PD1), anti-programmed cell death ligand 1 (PD-L1), or anti-PD-ligand 2 (L2) agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137); any other checkpoint inhibitor; bevacizumab; or any prior vaccine therapy.

Note: Other inclusion and exclusion criteria may apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Institut de Recherches Internationales Servier Clinical Studies Department +33 1 55 72 43 66 scientificinformation@servier.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05484622
Other Study ID Numbers  ICMJE CL1-95032-005
MK-3475-B39 ( Other Identifier: Merck Sharp & Dohme LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

  • Used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • Where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

  • Sponsored by Servier
  • With a first patient enrolled as of 1 January 2004 onwards
  • for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
URL: https://clinicaltrials.servier.com/
Current Responsible Party Servier ( Institut de Recherches Internationales Servier )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Institut de Recherches Internationales Servier
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Merck Sharp & Dohme LLC
Investigators  ICMJE Not Provided
PRS Account Servier
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP