Clinical Trials /

SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors

NCT03434262

Description:

Approximately 90% of children with malignant brain tumors that have recurred or relapsed after receiving conventional therapy will die of disease. Despite this terrible and frustrating outcome, continued treatment of this population remains fundamental to improving cure rates. Studying this relapsed population will help unearth clues to why conventional therapy fails and how cancers continue to resist modern advances. Moreover, improvements in the treatment of this relapsed population will lead to improvements in upfront therapy and reduce the chance of relapse for all. Novel therapy and, more importantly, novel approaches are sorely needed. This trial proposes a new approach that evaluates rational combination therapies of novel agents based on tumor type and molecular characteristics of these diseases. The investigators hypothesize that the use of two predictably active drugs (a doublet) will increase the chance of clinical efficacy. The purpose of this trial is to perform a limited dose escalation study of multiple doublets to evaluate the safety and tolerability of these combinations followed by a small expansion cohort to detect preliminary efficacy. In addition, a more extensive and robust molecular analysis of all the participant samples will be performed as part of the trial such that we can refine the molecular classification and better inform on potential response to therapy. In this manner the tolerability of combinations can be evaluated on a small but relevant population and the chance of detecting antitumor activity is potentially increased. Furthermore, the goal of the complementary molecular characterization will be to eventually match the therapy with better predictive biomarkers. PRIMARY OBJECTIVES: - To determine the safety and tolerability and estimate the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of combination treatment by stratum. - To characterize the pharmacokinetics of combination treatment by stratum. SECONDARY OBJECTIVE: - To estimate the rate and duration of objective response and progression free survival (PFS) by stratum.

Related Conditions:
  • Anaplastic Astrocytoma
  • Anaplastic Astrocytoma, IDH-Mutant
  • Anaplastic Ependymoma
  • Anaplastic Oligodendroglioma
  • Anaplastic Oligodendroglioma, IDH-Mutant and 1p/19q-Codeleted
  • Anaplastic Pleomorphic Xanthoastrocytoma
  • Atypical Teratoid/Rhabdoid Tumor
  • Central Nervous System Embryonal Neoplasm
  • Central Nervous System Ganglioneuroblastoma
  • Central Nervous System Neuroblastoma
  • Diffuse Glioma
  • Diffuse Midline Glioma, H3 K27M-Mutant
  • Embryonal Tumor with Multilayered Rosettes, C19MC-Altered
  • Embryonal Tumor with Multilayered Rosettes, Not Otherwise Specified
  • Ependymoma
  • Ependymoma, RELA Fusion-Positive
  • Glioblastoma
  • High-Grade Glioma, NOS
  • Malignant Glioma
  • Medulloblastoma
  • Medulloblastoma, Non-WNT/Non-SHH
  • Medulloblastoma, SHH-Activated
  • Medulloblastoma, WNT-Activated
  • Medulloepithelioma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors
  • Official Title: Molecularly-Driven Doublet Therapy for All Children With Refractory or Recurrent CNS Malignant Neoplasms and Young Adults With Refractory or Recurrent SHH Medulloblastoma

Clinical Trial IDs

  • ORG STUDY ID: SJDAWN
  • SECONDARY ID: NCI-2018-00284
  • NCT ID: NCT03434262

Conditions

  • Anaplastic Astrocytoma
  • Anaplastic Ependymoma
  • Anaplastic Ganglioglioma
  • Anaplastic Meningioma
  • Anaplastic Oligodendroglioma
  • Pleomorphic Xanthoastrocytoma, Anaplastic
  • Atypical Teratoid/Rhabdoid Tumor
  • Brain Cancer
  • Brain Tumor
  • Central Nervous System Neoplasms
  • Choroid Plexus Carcinoma
  • CNS Embryonal Tumor With Rhabdoid Features
  • Ganglioneuroblastoma of Central Nervous System
  • CNS Tumor
  • Embryonal Tumor of CNS
  • Ependymoma
  • Glioblastoma
  • Glioma
  • Glioma, Malignant
  • Medulloblastoma
  • Medulloblastoma; Unspecified Site
  • Medulloepithelioma
  • Neuroepithelial Tumor
  • Neoplasms
  • Neoplasms, Neuroepithelial
  • Papillary Tumor of the Pineal Region (High-grade Only)
  • Pediatric Brain Tumor
  • Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only)
  • Pineoblastoma
  • Primitive Neuroectodermal Tumor
  • Recurrent Medulloblastoma
  • Refractory Brain Tumor
  • Neuroblastoma. CNS
  • Glioblastoma, IDH-mutant
  • Glioblastoma, IDH-wildtype
  • Medulloblastoma, Group 3
  • Medulloblastoma, Group 4
  • Glioma, High Grade
  • Neuroepithelial Tumor, High Grade
  • Medulloblastoma, SHH-activated and TP53 Mutant
  • Medulloblastoma, SHH-activated and TP53 Wildtype
  • Medulloblastoma, Chromosome 9q Loss
  • Medulloblastoma, Non-WNT Non-SHH, NOS
  • Medulloblastoma, Non-WNT/Non-SHH
  • Medulloblastoma, PTCH1 Mutation
  • Medulloblastoma, WNT-activated
  • Ependymoma, Recurrent
  • Glioma, Recurrent High Grade
  • Glioma, Recurrent Malignant
  • Embryonal Tumor, NOS
  • Glioma, Diffuse Midline, H3K27M-mutant
  • Embryonal Tumor With Multilayered Rosettes (ETMR)
  • Ependymoma, NOS, WHO Grade III
  • Ependymoma, NOS, WHO Grade II
  • Medulloblastoma, G3/G4
  • Ependymoma, RELA Fusion Positive

Interventions

DrugSynonymsArms
GemcitabineGemzar®A: ribociclib + gemcitabine
ribociclibLEE011, LEE-011, KISQALI®A: ribociclib + gemcitabine
sonidegibLDE225, LDE-225, ODOMZO®C: ribociclib + sonidegib
trametinibTMT212, TMT-212, MEKINIST(TM)B: ribociclib + trametinib
filgrastimG-CSFA: ribociclib + gemcitabine

Purpose

Approximately 90% of children with malignant brain tumors that have recurred or relapsed after receiving conventional therapy will die of disease. Despite this terrible and frustrating outcome, continued treatment of this population remains fundamental to improving cure rates. Studying this relapsed population will help unearth clues to why conventional therapy fails and how cancers continue to resist modern advances. Moreover, improvements in the treatment of this relapsed population will lead to improvements in upfront therapy and reduce the chance of relapse for all. Novel therapy and, more importantly, novel approaches are sorely needed. This trial proposes a new approach that evaluates rational combination therapies of novel agents based on tumor type and molecular characteristics of these diseases. The investigators hypothesize that the use of two predictably active drugs (a doublet) will increase the chance of clinical efficacy. The purpose of this trial is to perform a limited dose escalation study of multiple doublets to evaluate the safety and tolerability of these combinations followed by a small expansion cohort to detect preliminary efficacy. In addition, a more extensive and robust molecular analysis of all the participant samples will be performed as part of the trial such that we can refine the molecular classification and better inform on potential response to therapy. In this manner the tolerability of combinations can be evaluated on a small but relevant population and the chance of detecting antitumor activity is potentially increased. Furthermore, the goal of the complementary molecular characterization will be to eventually match the therapy with better predictive biomarkers. PRIMARY OBJECTIVES: - To determine the safety and tolerability and estimate the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of combination treatment by stratum. - To characterize the pharmacokinetics of combination treatment by stratum. SECONDARY OBJECTIVE: - To estimate the rate and duration of objective response and progression free survival (PFS) by stratum.

Detailed Description

      Patients will be stratified by the molecular and histologic characteristics of their tumor to
      one of three treatment strata.

      STRATUM A:

        -  Combination Treatment: ribociclib and gemcitabine.

        -  Patient Population: Participants with a diagnosis of refractory or recurrent
           medulloblastoma (Group 3/4) or refractory or recurrent ependymoma (including:
           ependymoma, not otherwise specified (NOS), WHO Grade III; ependymoma, RELA fusion
           positive; anaplastic ependymoma; ependymoma, NOS, WHO grade II).

      STRATUM B:

        -  Combination Treatment: ribociclib and trametinib.

        -  Patient Population: Participants with a diagnosis of one of the following refractory or
           recurrent CNS diseases: medulloblastoma [sonic hedgehog (SHH)], medulloblastoma (WNT),
           high grade glioma (including: high grade glioma, (NOS), WHO Grade III or IV; anaplastic
           astrocytoma, IDH mutant; glioblastoma, IDH-wildtype; glioblastoma, IDH-mutant; diffuse
           midline glioma, H3K27-mutant; anaplastic oligodendroglioma, IDH mutant and
           1p/19q-codeleted; anaplastic pleomorphic xanthoastrocytoma) or select central nervous
           system (CNS) embryonal tumors (including: embryonal tumors with multilayered rosettes,
           C19MC-altered; embryonal tumors with multilayered rosettes, not otherwise specified
           (NOS); medulloepithelioma; CNS neuroblastoma; CNS ganglioneuroblastoma; CNS embryonal
           tumor, NOS; atypical teratoid/rhabdoid tumor; CNS embryonal tumor with rhabdoid
           features).

      STRATUM C:

        -  Combination Treatment: ribociclib and sonidegib.

        -  Patient Populations: Participants with refractory or recurrent medulloblastoma (SHH) >6
           months off smoothened inhibitor, presence of 9q loss or PTCH1 mutant, skeletally mature.

      The rolling 6 design will be used separately in each stratum to estimate the MTD or RP2D and
      determine the dose-limiting toxicity (DLT) of the combination of escalating doses. Therapy
      will be administered in cycles of 28 days and may be continued for up to 24 months (26
      cycles) in the absence of disease progression or unacceptable toxicity.

      Patients will receive doublet therapy in cycles of 28 days. The dose-limiting toxicity
      (DLT)-evaluation period will consist of the first cycle (i.e. first 4 weeks of therapy).
      Research participants will be evaluated at least once a week during the DLT-evaluation period
      and at regular intervals thereafter. Standard (e.g., physical exam, blood tests, and disease
      evaluations) tests will be obtained at regular intervals. Research-associated evaluations
      (e.g., pharmacokinetic studies, etc.) will also be obtained during therapy. Treatment may be
      continued for up to 2 years in the absence of disease progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
A: ribociclib + gemcitabineExperimentalStratum A participants with a diagnosis of refractory or recurrent medulloblastoma (Group 3/4) or refractory or recurrent ependymoma. (including: ependymoma, not otherwise specified (NOS), WHO Grade III; ependymoma, RELA fusion positive; anaplastic ependymoma; ependymoma, NOS, WHO grade II). They receive combination treatment with ribociclib and gemcitabine. They may also receive growth therapy support with filgrastim.
  • Gemcitabine
  • ribociclib
  • filgrastim
B: ribociclib + trametinibExperimentalStratum B participants with a diagnosis of one of the following refractory or recurrent CNS diseases: medulloblastoma, [sonic hedgehog (SHH)- or WNT-activated];; high grade glioma (including: high grade glioma, (NOS), WHO Grade III or IV; anaplastic astrocytoma, IDH mutant; glioblastoma, IDH-wildtype; glioblastoma, IDH-mutant; diffuse midline glioma, H3K27-mutant; anaplastic oligodendroglioma, IDH mutant and 1p/19q-codeleted; anaplastic pleomorphic xanthoastrocytoma); select CNS embryonal tumors (including: embryonal tumors with multilayered rosettes, C19MC-altered; embryonal tumors with multilayered rosettes, NOS; medulloepithelioma; CNS neuroblastoma; CNS ganglioneuroblastoma; CNS embryonal tumor, NOS; atypical teratoid/rhabdoid tumor; CNS embryonal tumor with rhabdoid features). They receive combination treatment with ribociclib and trametinib.
  • ribociclib
  • trametinib
C: ribociclib + sonidegibExperimentalStratum C participants with refractory or recurrent medulloblastoma (SHH-activated) >6 months off smoothened inhibitor, presence of 9q loss or PTCH1 mutant, skeletally mature. They received combination treatment with ribociclib and sonidegib.
  • ribociclib
  • sonidegib

Eligibility Criteria

        Potential participants will first be screened using the screening inclusion/exclusion shown
        below. If they meet the requirements of the screening phase, they will then be evaluated
        for enrollment based on the overall study's inclusion criteria as well as the
        stratum-specific inclusion/exclusion criteria for the applicable stratum, all of which are
        shown below.

        SCREENING INCLUSION CRITERIA - ALL PARTICIPANTS:

          -  Participants with recurrent, progressive, or refractory brain tumors.

          -  Age ≥ 1 year and < 25 years at the time of screening. Exception: Participants with
             recurrent, progressive, or refractory Medulloblastoma and are ≥ 1 and < 40 years of
             age at the time of study screening are eligible for screening.

          -  Participants and/or guardian have the ability to understand and the willingness to
             sign a written informed consent document according to institutional guidelines.

        SCREENING EXCLUSION CRITERIA - ALL PARTICIPANTS:

          -  Participants with a diagnosis of recurrent, progressive, or refractory low grade
             glioma (LGG).

          -  Previous exposure to a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib).

          -  Participants with a history of clinically significant, uncontrolled heart disease
             and/or repolarization abnormalities.

          -  Participants with any history of QTc prolongation (i.e. QTc interval of > 450 msec).

        Participants who meet the requirements of the screening phase will then be evaluated for
        enrollment based on the overall study's inclusion criteria as well as the stratum-specific
        inclusion/exclusion criteria for the applicable stratum, all of which are shown below.

        INCLUSION CRITERIA - OVERALL STUDY - ALL PARTICIPANTS:

          -  Evaluable disease, as defined as meeting any of the following:

               -  Patients who have measurable disease

               -  Patients with radiologically discernible but non-measurable lesions (i.e.
                  leptomeningeal disease)

               -  Patients with CSF positive disease

          -  Participants must have received their last dose of anticancer therapy (including
             experimental) at least 4 weeks prior to study enrollment.

               -  Note: Participants must have relapsed with recurrent, progressive or refractory
                  disease on or after any prior anticancer therapy.

          -  Participants must have had their last fraction of radiation at least 4 weeks prior to
             study enrollment. Participants who received radiation therapy for palliation must have
             had their last fraction of radiation at least 2 weeks prior to study enrollment.

               -  Note: Participants must have relapsed with recurrent, progressive or refractory
                  disease after any prior radiation therapy that is not considered palliative.
                  Palliative radiation therapy is defined as local small port RT to alleviate
                  and/or palliate symptoms. (CSI, whole brain RT, large field/port RT, or large
                  field/port multilevel spinal RT will not be considered palliative at any dose.)

          -  Participants who are receiving corticosteroids must be on a stable or decreasing dose
             for at least 1 week prior to study enrollment with no plans for escalation.

          -  Participants who are receiving known strong inducers and/or strong inhibitors of
             CYP3A4/5, drugs that have a narrow therapeutic window and are predominantly
             metabolized through CYP3A4/5, and medications that carry a known risk for QT
             prolongation must discontinue these drugs at least 7 days prior to study enrollment.

          -  Participants must discontinue herbal preparations, herbal medication, and dietary
             supplements, with the exception of multivitamins, at least 7 days prior to study
             enrollment.

          -  Participants must be able to swallow medication. It is acceptable to administer
             medication via a g-tube if participant has a g-tube. It is not acceptable to place a
             g-tube for the purpose of delivering study medication.

          -  Participants must have a Lansky (≤ 16 years) or Karnofsky (> 16 years) score of at
             least 50 and, in the opinion of the investigator, a minimum life expectancy of at
             least 6 weeks at the time of study enrollment.

               -  Note: Patients who are unable to walk because of paralysis, but who are up in a
                  wheelchair, will be considered ambulatory for the purpose of assessing the
                  performance score.

          -  Participant must have adequate bone marrow and organ function defined as:

               -  ANC ≥ 1000/mm3 without growth factor support within 7 days of the test

               -  Platelet count ≥ 50,000/mm^3 without support of a platelet transfusion within 7
                  days of the test

               -  Hemoglobin ≥ 8.0 g/dL without support of a blood transfusion within 7 days of the
                  test

               -  Creatinine clearance ≥ 70 mL/min/1.73 m^2 or serum creatinine ≤ the maximum serum
                  creatinine based on age/gender (threshold creatinine values derived from the
                  Schwartz formula for estimating GFR utilizing child length and stature data
                  published by the Centers for Disease Control and Prevention or creatinine
                  clearance ≥70 mL/min/1.73 m^2).

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
                  For the purposes of eligibility the ULN of ALT and AST is 45 U/L.

               -  Total bilirubin ≤ ULN or if > ULN then direct bilirubin ≤ 1.5xULN.

          -  Participants and/or guardian have the ability to understand and the willingness to
             sign a written informed consent document according to institutional guidelines.

        EXCLUSION CRITERIA - OVERALL STUDY - ALL PARTICIPANTS:

          -  Participants receiving any other investigational agents.

          -  Participants with other clinically significant medical disorders (serious infections
             or significant cardiac, pulmonary, hepatic, psychiatric, GI disease, or other organ
             dysfunction) that in the investigator's judgment could compromise their ability to
             tolerate or absorb protocol therapy or would interfere with the study procedures or
             results.

          -  Female participants who are breastfeeding a child.

          -  Participants with QTc interval of > 450 msec on screening ECG.

          -  Participants with a pathogenic somatic or known germline retinoblastoma (RB1) gene
             mutation.

        (A) INCLUSION CRITERIA - STRATUM A PARTICIPANTS ONLY:

          -  Participants with recurrent, progressive, or refractory Non-WNT Non-SHH (NWNS)
             Medulloblastoma or Ependymoma as confirmed through central pathology review.

          -  Age ≥ 1 year and < 25 years at the time of enrollment.

          -  Female participants of childbearing potential must have a negative pregnancy test at
             the time of enrollment on this study and be willing to use a highly effective method
             of contraception throughout the study and for 16 weeks after discontinuation of the
             study drug.

          -  Male participants of child fathering potential must be willing to use medically
             acceptable form of contraception during treatment and for 16 weeks after stopping
             treatment.

        (A) EXCLUSION CRITERIA - STRATUM A PARTICIPANTS ONLY:

          -  Participants with subependymoma or myxopapillary ependymoma.

        (B) INCLUSION CRITERIA - STRATUM B PARTICIPANTS ONLY:

          -  Participants with recurrent, progressive, or refractory CNS tumors as confirmed
             through central pathology review and whose diagnosis is being treated on this study.

          -  Age ≥ 1 year and < 25 years at the time of study enrollment.

          -  Must meet the following weight and BSA restrictions:

               -  For enrollment on dose levels 0A, must have a weight ≥16kg and <32kg.

               -  For enrollment on dose level 0B, must have a weight of ≥32kg and BSA ≥ 0.55m^2.

               -  For enrollment on dose level 1, must have a weight ≥16kg and BSA ≥0.55m^2.

               -  For enrollment on dose level 2, must have a weight ≥16kg and BSA≥ 0.63m^2

               -  For enrollment on dose levels 3 or 4A, must have a weight ≥16kg

               -  For enrollment on dose levels 4B or 5, must have a weight ≥20kg and ≤106kg

          -  Participant must be able to swallow trametinib tablets.

          -  Female participants of childbearing potential must have a negative pregnancy test at
             the time of enrollment on this study and be willing to use a highly effective method
             of contraception throughout the study and for 16 weeks after discontinuation of the
             study drug.

          -  Male participants of child fathering potential must be willing to use medically
             acceptable form of contraception during treatment and for 16 weeks after stopping
             treatment.

        (B) EXCLUSION CRITERIA - STRATUM B PARTICIPANTS ONLY: Participants eligible for this study
        must NOT meet ANY of the following criteria.

          -  Participants with Low Grade Glioma (LGG) or Diffuse Intrinsic Pontine Glioma (DIPG).

          -  Previous exposure to a MEK inhibitor (i.e. trametinib, selumetinib).

          -  Participants with abnormal LVEF on screening, defined as > 10% below lower limit of
             normal on screening.

          -  Participants with retinal vein occlusion (RVO).

          -  Previous exposure to a MEK inhibitor (i.e., trametinib, selumetinib.

        (C) INCLUSION CRITERIA - STRATUM C PARTICIPANTS ONLY:

          -  Participants with recurrent, progressive, or refractory SHH Medulloblastoma and
             presence of either a or b as confirmed by central pathology review of the tumor
             specimen: a) copy number loss of 9q b) PTCH1 mutation and whose diagnosis is being
             treated on this study.

          -  Age ≥ 10 years and <40 years at the time of study enrollment.

          -  Participant must be skeletally mature as defined as females with a bone age ≥ 15 years
             (180 months) and males with a bone age ≥ 17 years (204 months). This includes
             participants that are within 2 standard deviations of this value (i.e. if SD = 11
             months on bone age; then a male patient who has a bone age of 182 months would be
             eligible; or a female patient with a bone age of 158 months.)

          -  Female participants of childbearing potential must have a negative pregnancy test at
             the time of enrollment on this study and be willing to use a highly effective method
             of contraception throughout the study and for 8 months after discontinuation of the
             study drug.

          -  Male participants of child fathering potential must be willing to use medically
             acceptable form of contraception during treatment and for 8 months after stopping
             treatment.

        (C) EXCLUSION CRITERIA - STRATUM C:

          -  Exposure to smoothened inhibitor (vismodegib, sonidegib) within the last 6 months.
      
Maximum Eligible Age:39 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Estimate the Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) of each doublet by stratum
Time Frame:1 month after start of therapy
Safety Issue:
Description:The MTD is empirically defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level has been determined to be too toxic. The MTD estimate will not be available, if the lowest dose level studied is too toxic or the highest dose level studied is considered safe. In the latter case, the highest studied safe dose will be considered the recommended phase 2 dose (RP2D). The MTD estimation will be limited to evaluable patients and toxicity assessments from course 1 (28 days).

Secondary Outcome Measures

Measure:Response rate by stratum
Time Frame:Up to 1 year after completion of therapy (up to 3 years after start of therapy)
Safety Issue:
Description:The response rate, defined as the rate of complete response (CR) or partial response (PR), and long-term stable disease (SD) will be calculated as the percentage of confirmed responders among all response assessable patients. These rates as well as their exact confidence intervals will be provided and will be summarized by each response category (i.e., CR, PR, and SD). Descriptive summaries of response per dose level may also be provided. Subjects without an assessment will be considered non-responders.
Measure:Duration of objective response by stratum
Time Frame:Up to 1 year after completion of therapy (up to 3 years after start of therapy)
Safety Issue:
Description:Duration of response defined as the time from the initial documented response (CR or PR) to the first confirmed progressive disease (PD). We will use progression free survival (PFS) for describing duration of SD. Subjects without a documented progression will be censored at the time of their last tumor assessment. Duration of Response will be assessed using the Kaplan-Meier method to calculate the median time as well as the proportion remaining progression free at given time points. The corresponding 95% confidence intervals will be presented.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:St. Jude Children's Research Hospital

Trial Keywords

  • ATRT
  • Brain Tumors in Adolescents
  • Brain Tumors in Children
  • Brain Tumors in Young Adults
  • CDK4 amplification
  • CDK 4/6
  • CDK 4/6 inhibitor
  • CDK 4/6 pathway
  • CDK 4/6/cyclin/RB/E2F pathway
  • CDK6 amplification
  • CyclinD1
  • DAWN
  • D-type Cyclins
  • Hedgehog pathway inhibitor
  • HGG
  • MAPK pathway
  • MEK
  • MEK inhibitor
  • MEK1
  • MEK2
  • Mekinist
  • Molecular
  • Molecular therapy
  • MYC amplification
  • PTCH1
  • Rare brain tumor
  • Recurrent ATRT
  • Recurrent brain tumor
  • Recurrent ependymoma
  • Recurrent high grade glioma
  • Recurrent malignant glioma
  • Recurrent medulloblastoma
  • Refractory brain tumor
  • Small molecule inhibitor
  • SMO antagonist
  • Smoothened protein
  • Sonic hedgehog
  • Combination therapy

Last Updated

January 23, 2020