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Clinical Trial 19648

Cancer Type: Neurologic Oncology
Interventions:Avelumab; MSB00100718C (Avelumab)

Study Type: Treatment
Phase of Study: Phase I

  • Peter Forsyth

Call 813-745-6100
or 1-800-679-0775

Study Title

Phase IB Study of Avelumab with Radiotherapy in Patients with Leptomeningeal Disease



Objectives: Primary Objectives: To establish the safety of combination of Avelumab and WBRT in patients with LMDz and perform exploratory analysis of the patient survival rate. Secondary Objectives: To gather preliminary data regarding clinical outcomes of the study therapy Endpoints: Primary Endpoints: 1) Safety and dose limiting toxicities. 2) The proportion of patients surviving at least 15 weeks after the first dose of Avelumab. Secondary Endpoints: 1) The number and activation status of T cells and the CSF cytokine activation profile in the CSF (relative to serum and relative to collection time), measured before and after Avelumab administration; 2) LMDz/central nervous system response rate and systemic (i.e., non-central nervous system) response rates; 3) the association between serum/CSF levels of Avelumab/activated T-cell responses and clinical toxicities and responses; 4) overall survival and progression-free survival; 5) the association between enumerated CSF circulating tumor cells, conventional CSF cytology, and response rates; 6) evolution of clinical status associated with the cardinal CSF biomarkers; and 7) levels of Avelumab in the serum and CSF.

Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of melanoma, lung cancer, or breast cancer
  • Leptomeningeal disease and a histologic diagnosis of melanoma, lung cancer, or breast cancer.
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance scale of ≤ 2
  • An interval of at least 2 weeks after the end of prior radiation therapy to the brain.
  • An interval of at least 4 weeks following any surgical resection of brain lesions prior to treatment
  • An interval of at least 4 weeks after the last administration of any investigational agent, bevacizumab, immunotherapy, or prior cytotoxic agents
  • 18 years of age or older on the day of signing consent
  • Demonstrate adequate organ function.
  • Resting baseline O2 saturation by pulse oximetry of ≥ 92% at rest
  • Participants must have recovered from the toxic effects of prior therapies (≤ Grade 1)
  • Life expectancy of greater than or equal to 8 weeks
  • Pregnancy test: negative serum or urine pregnancy test at screening for women of childbearing potential. Must be repeated once-monthly during treatment with Avelumab, at the end of study study treatment, at 30 ±3, 60 ±3, and 90 ±3 days follow-up and additionally whenever 1 menstrual cycle is missed or when potential pregnancy is otherwise suspected.
  • Contraception: Highly effective contraception for both male and female subjects throughout the study and for at least 30 days after last Avelumab treatment administration, if the risk of conception exists.

  • Exclusion Criteria

  • Participants receiving other treatments specifically administered to treat LMDz. Some exclusions apply.
  • Clinical evidence of obstructive hydrocephalus or compartmentalization of the CSF flow
  • Participants with a ventriculoperitoneal or ventriculoatrial shunt must have an on/off device in their shunt systems to be eligible for the study. Participants must be able to tolerate shunt closure for ~4 hours without development of clinical signs of increased intracranial pressure.
  • Unable or unwilling to have a contrast-enhanced brain MRI.
  • Currently participating in or having participated in a study of an investigational agent or device ≤ 4 weeks prior to the first dose of study treatment.
  • Currently participating in or having participated in a study of an investigational agent or use of an investigational device within 4 weeks of the first dose of treatment.
  • Diagnosis of immunodeficiency or receipt of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Physiologic doses of steroid therapy (> Prior chemotherapy, targeted small molecule therapy, or monoclonal antibody within 4 weeks prior to study Day 1 or nonrecovery (i.e., 4 weeks earlier.
  • Known additional malignancy that is progressing or requires active treatment. Some exceptions apply.
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Some exceptions apply.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Had major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of treatment on study.
  • Requires escalating or chronic supraphysiologic doses of corticosteroids (> 10 mg/day prednisone equivalents).
  • Has a history of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has 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).
  • Other exclusions apply