Neurologic Cancer MSK 20-091

The purpose of this study is to assess the safety and effectiveness of combining three drugs to treat people with an IDH-mutant glioma that came back after chemotherapy or surgery. The three medications are pembrolizumab, olaparib, and temozolomide. 

Study assessments will be conducted at baseline, post-chemotherapy/end of intervention and at 1-year post diagnosis. Women who are prescribed neoadjuvant therapy will have additional assessments prior to surgery.

Inclusion Criteria:

  • Histologically confirmed grade II or III IDH-mutated glioma that has recurred after first line therapy. There is no limit on the number of prior therapies or types of therapies patients can have received.
  • Measurable disease by RANO criteria
  • Stable dose of corticosteroids for ≥ 4 weeks prior to baseline MRI. Steroid dose not to exceed 2mg/day dexamethasone (or equivalent).
  •  Age 18 or older
  • Patients or their Legally Authorized Representative (LAR) must provide written informed consent prior to any screening procedures.
  • Willing and able to comply with scheduled visits, treatment plan, and laboratory tests
  • Patient must be able to swallow and retain oral medication
  • Patient must have adequate organ function.
  • Before starting study treatment, patients must have recovered to grade 1 from prior therapy (except for residual alopecia or grade 2 peripheral neuropathy).
  • Patients must be able to undergo contrast-enhanced MRI scans.
  • Patients must have shown unequivocal evidence for tumor progression by MRI in comparison to a prior scan
  • At least 12 weeks elapsed since prior radiotherapy
  • Life expectancy greater than 12 weeks
  • A woman of childbearing potential (WOCBP) must not have a positive urine pregnancy test within 72 hours prior to allocation. Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 12 months after the last dose of the study therapy.
  • Male participants must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days following the last dose of study treatment and refrain from donation sperm during this period.
  • Women must agree not to breast feed while on therapy and for at least 120 days following the last dose of study drug.

Exclusion Criteria:

  • No limit on number of prior therapies
  • Evidence of significant intracranial hemorrhage
  • No other investigational or standard anti-tumor therapy allowed
  • Patients must not have a known history of allergic reaction attributed to study drugs or compounds of similar chemical or biologic composition unless allergic reaction was managed by pre-medication.
  • Patients must not have a serious pre-existing medical condition or uncontrolled intercurrent illness that would preclude participation in this study (for example, uncontrolled ventricular arrhythmia, interstitial lung disease, severe dyspnea at rest of requiring oxygen therapy, history of major surgical resection involving the stomach or bowel, or pre-existing Crohn's disease or ulcerative colitis or other autoimmune disease,) or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients must not have a diagnosis of immunodeficiency or be receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  • Patients must not have an active systemic fungal and/or known viral infection (for example human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies).
  • Patients must not have a history of active tuberculosis.
  • Patients must not have an active infection requiring systemic therapy
  • Patients must not have known history of, or any evidence of active, non-infectious pneumonitis
  • Concomitant use of known strong CYP3A inhibitors (itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir)
  • Concomitant use of known strong CYP3A inducers (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St. John's Wort)
  • A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to allocation.
  • Patients must not have other active concurrent malignancy. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Patients must not have active autoimmune disease that required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
  • Patients must not have received a live vaccine within 30 days of planned start of study (Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccine and are not allowed)
  • Concurrent treatment on another clinical trial. Supportive care trials or nontherapeutic trials (i.e. quality of life) are allowed.

Location: HH

Contact: Sierra Cugno 860.972.4062 [email protected]

Sponsor: Memorial Sloan Kettering Cancer Center

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