Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Neoplasms, Germ Cell and Embryonal

Disease Attributes

Astrocytoma

Neoplasms, Nerve Tissue

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Oligodendroglioma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neuroepithelioma

Vorasidenib

Servier Pharmaceuticals LLC

Jonathan Dewey, MD

This is an expanded access program to provide vorasidenib for treatment of patients 12 years or older with IDH1- or IDH2-mutated glioma.

This expanded access program is designed to provide access to vorasidenib for patients with IDH1- or IDH2-mutated glioma who are not eligible for other vorasidenib clinical trials, and who in the opinion of the treating oncologist would potentially benefit from treatment with vorasidenib.

Safety assessments (including vital signs, hematology, and serum chemistry) occur every two weeks for the first two cycles (28 day each cycle), then monthly for the duration of treatment. Treatment with vorasidenib will continue until, in the clinical judgement of the treating physician, the patient is no longer benefiting from the treatment, vorasidenib is approved and available by prescription, or the study is terminated.

Requests by treating physicians to file a single patient investigational new drug application as part of the expanded access program for vorasidenib will be considered on a case-by-case basis.

Vorasidenib Expanded Access Program

The Expanded Access Use of Vorasidenib in Patients With IDH1 or IDH2 Mutated Glioma

Servier Pharmaceuticals, LLC

Servier

Nervous System Diseases

Brain Neoplasms

All Drugs and Chemicals

Vaccines

Immunomodulating Agents

Patients will receive vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids) intramuscularly into the deltoid muscle. Patients will then receive vorasidenib 40mg orally once a day for 28 days. After two cycles of 28-day vorasidenib and at the start of the 3rd cycle of vorasidenib, patients will receive the PEPIDH1M vaccine intradermally (i.d.) to alternating groin regions on the following schedule: vaccine #1, day 1; vaccine #2, day 15. The day before vaccine #1, patients will receive a vaccine site pre-conditioning injection of a single dose of Td toxoid. This will be administered twelve hours to one day prior to receiving PEPIDH1M vaccine i.d. to the RIGHT groin area. Vaccines #3 and #4 will be given on day 1 and day 15 of cycle 4. Starting on 6th cycle of 28-day vorasidenib, subjects will receive PEPIDH1M vaccine (i.d. to alternating groin regions) every 28 days on day 1 for vaccine #5-#12. Patients will receive up to a total of 14 cycles of vorasidenib.

PEPIDH1M vaccine + vorasidenib

Katherine Peters, MD, PhD

Stevie Threatt

The purpose of this study is to determine the safety and efficacy of a PEPIDH1M vaccine in combination with vorasidenib, a dual inhibitor of mutant IDH1 and IDH2 enzymes, in adult patients diagnosed with recurrent IDH1 mutant lower grade gliomas.

This study is designed to assess the safety and efficacy of the PEPIDH1M vaccine in combination with vorasidenib in adult patients recurrent IDH1 mutant lower grade gliomas. Patients will receive vaccination with 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly (I.M.) into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Patients will then receive vorasidenib 40 mg orally once a day for 28 days. After two cycles of 28-day vorasidenib and at the start of the 3rd cycle of vorasidenib, patients will receive the PEPIDH1M vaccine intradermally (i.d.) to alternating groin regions on the following schedule: vaccine #1, day 1; vaccine #2, day 15. The day before vaccine #1, patients will receive a vaccine site pre-conditioning injection of a single dose of Td toxoid (1 flocculation unit \[Lf\] in a total volume of 0.4 mL saline). This will be administered twelve hours to one day prior to receiving PEPIDH1M vaccine i.d. to the RIGHT groin area. Vaccines #3 and #4 will be given on day 1 and day 15 of cycle 4. Starting on 6th cycle of 28-day vorasidenib, subjects will receive PEPIDH1M vaccine (i.d. to alternating groin regions) every 28 days on day 1 for vaccine #5-#12. Patients will receive up to a total of 14 cycles of vorasidenib. Notably, a safety lead-in will be performed before commencing on the full study to assess the safety of the combination and evaluation for any dose-limiting toxicity (DLT).

The most common side effects of peptide vaccines are redness or swelling at the injection site, local changes to the texture of skin (hardening) at the injection site, itching, allergic reactions, and a potentially serious side effect called cytokine release syndrome. The most common side effects of vorasidenib are abnormal liver function tests, QT prolongation, stomach and/or intestinal ulcers, neurologic disturbances, skin peeling, and isocitrate dehydrogenase (IDH) differentiation syndrome.

All patients who receive any protocol treatment will be included in either primary or secondary efficacy analyses. Statistical analyses for the primary objective of adverse experience will exclude patients who terminate protocol treatment prematurely (i.e., less than 4 vaccinations) without an unacceptable toxicity.

ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas

The proportion of patients with an unacceptable toxicity

The time between initiation of cycle 1 vorasidenib and first documentation of disease progression or death

Katy Peters, MD, PhD

Sponsor-Investigator

Antineoplastic Agents

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

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.

Participants will receive vorasidenib orally, QD from Day 1 to 28 of a 28-day cycle prior to surgery.

Participants will not receive any treatment prior to surgery.

Institut de Recherches Internationales Servier Clinical Studies Department

Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive enhancing isocitrate dehydrogenase-1 (IDH-1) mutant Glioma.

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.

Sequential design for safety lead-in and randomized perioperative phases, parallel design within randomized perioperative phase.

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

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

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.

TIL is defined as the percentage of tumor-infiltrating lymphocyte cells on a logarithmic scale.

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.

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.

Merck Sharp & Dohme LLC

Institut de Recherches Internationales Servier

Vorasidenib 40 mg, continuous daily dosing.

Matching placebo 40 mg, continuous daily dosing.

Matching Placebo

Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment. Participants will be required to have central confirmation of IDH mutation status prior to randomization. Approximately 340 participants are planned to be randomized 1:1 to receive orally administered vorasidenib 40 mg QD or placebo.

Participants randomized in a 1:1 allocation (vorasidenib vs Placebo)

Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study of AG-881 in Subjects With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation

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.

PFS is defined as the time from date of randomization to date of first documented radiographic PD (as assessed by the blinded independent review committee (BIRC) per modified Response Assessment for Neuro-oncology for Low-Grade Gliomas or date of death due to any cause, whichever occurs earlier.

All AEs and SAEs were to be recorded starting at the first dose of IMP through 28 days after the last dose of IMP. After the 28-day follow-up period, only SAEs that were considered to be related to IMP were reported in the safety database.

Vorasidenib 40 mg, continuous daily dosing.

Vorasidenib: Vorasidenib oral film-coated tablets

Matching placebo 40 mg, continuous daily dosing.

Matching Placebo: Matching Placebo oral tablets

Total

Age, Continuous

Participant Age

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

Canada

Netherlands

United States

Italy

United Kingdom

Israel

France

Switzerland

Germany

Spain

Region of Enrollment

BMI (kg/m^2)

Clinical Studies Department

Progression-Free Survival (PFS)

Matching placebo 40 mg, continuous daily dosing. Matching Placebo: Matching Placebo oral tablets

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vorasidenib Expanded Access Program	NCT05592743	Glioma Recurrence Disease Attribu... Pathologic Proc... Neoplasms, Neur... Neuroectodermal... Neoplasms, Germ... Neoplasms by Hi... Neoplasms Neoplasms, Glan... Neoplasms, Nerv...	Vorasidenib	12 Years -	Servier
ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas	NCT05609994	Low Grade Gliom...	PEPIDH1M vaccin...	18 Years -	Duke University
Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive Enhancing IDH-1 Mutant Glioma	NCT05484622	Astrocytoma	Vorasidenib Pembrolizumab	18 Years -	Servier
Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive Enhancing IDH-1 Mutant Glioma	NCT05484622	Astrocytoma	Vorasidenib Pembrolizumab	18 Years -	Servier
Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)	NCT04164901	Grade 2 Glioma Residual Glioma Recurrent Gliom...	Vorasidenib Matching Placeb...	12 Years -	Servier
ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas	NCT05609994	Low Grade Gliom...	PEPIDH1M vaccin...	18 Years -	Duke University
Vorasidenib Expanded Access Program	NCT05592743	Glioma Recurrence Disease Attribu... Pathologic Proc... Neoplasms, Neur... Neuroectodermal... Neoplasms, Germ... Neoplasms by Hi... Neoplasms Neoplasms, Glan... Neoplasms, Nerv...	Vorasidenib	12 Years -	Servier

Spots Global Cancer Trial Database for vorasidenib

Every month we try and update this database with for vorasidenib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for vorasidenib

Every month we try and update this database with for vorasidenib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for vorasidenib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.