for people ages 1-39 (full criteria)
at San Francisco, California and other locations
study started
completion around
Principal Investigator
by Sabine Mueller, MD, PhD, MAS
Headshot of Sabine Mueller
Sabine Mueller



The current study assesses the tolerability and efficacy of combination therapy with PD-1 (nivolumab) and pan-RAF-kinase (DAY101) inhibition for the treatment of children and young adults with craniopharyngioma.

Official Title

Nivolumab and DAY101 for the Treatment of Newly Diagnosed or Recurrent Craniopharyngioma in Children and Young Adults



  1. To determine progression free survival and maintenance of quality of life at 12 months as based on physical function and compared to historical controls.


  1. To identify proportion of participants with visual deficits at 1-year, 2-year, and 3-year follow-up.

II. To identify proportion of participants with neuroendocrine deficits at 1-year, 2-year, and 3-year follow-up.


  1. To assess Quality of Life (QOL) and cognitive measures in children and young adults with newly diagnosed or recurrent craniopharyngioma.

II. To perform Immunohistochemistry (IHC)/Multiplexed ion beam imaging on pre-and post-treatment tumor tissue (as available), including at time of progression, to assess for patterns of protein density and spatial relationship in intact tumor tissue and elucidate changes in tumor tissue over the course of therapy and disease evolution.

III. To perform single-cell (scRNA) and single-nucleus (snRNA) RNA sequencing on pre- and post-treatment tumor tissue (as available), including at time of progression, to identify and characterize distinct cell subsets that make up the components of craniopharyngioma and elucidate changes in cell subsets over the course of therapy and disease evolution.

IV. To perform proteomic analysis on pre- and post-treatment tumor tissue, including at time of progression, to characterize distinct proteins and transcriptome pathways that are active in different tumor compartments and elucidate changes in proteomic profiles over the course of therapy and disease evolution.

  1. To perform ELISA array/multiplex analysis on pre- and post-treatment cyst fluid, including at time of progression, to characterize distinct cytokine profiles and elucidate changes in cytokine profile over the course of therapy and disease evolution.

VI. Microbiome and flow cytometry studies in the context of imaging and clinical outcomes using descriptive statistic.


Participants will be divided into 2 Groups (Newly diagnosed craniopharyngioma, Recurrent craniopharyngioma) with 3 treatment arms within each group (Neoadjuvant nivolumab, Neoadjuvant DAY101, Neoadjuvant combination nivolumab plus DAY101). There will also be a separate Non-biopsy/resection arm within the Recurrent Craniopharyngioma group.

Participants will be randomized in a 1:1:1 and will receive one dose of assigned drug prior to planned biopsy or resection. Participants with measurable disease will then continue on combination maintenance therapy. Participants may continue treatment for up to 24 months total and will be followed up 3 years after enrollment into the study.


Craniopharyngioma, Child, Craniopharyngioma, Recurrent Craniopharyngioma, Neoadjuvant therapy, Adamantinoma, Nivolumab, DAY101


You can join if…

Open to people ages 1-39

Newly Diagnosed Participants:

  • Newly diagnosed craniopharyngioma diagnosis based on imaging characteristics and central radiology review. Participants will initially be screened within confines of a screening consent and only those participants with findings consistent with craniopharyngioma and without findings suggesting an indeterminate lesion or lesion of an alternative diagnosis (including abnormal tumor markers found in blood or cerebral spinal fluid (CSF), if completed as part of standard of care (SOC) work-up or if lesion concerning for alternate diagnosis) will move ahead with enrollment on the treatment protocol. Additionally, for patients that have undergone initial biopsy to confirm diagnosis, are within 4 weeks of radiographic diagnosis, and are planned to undergo follow up second surgery for additional tumor resection as per standard of care recommendations, these patients will also be considered eligible.
  • Participants must be surgical candidates for biopsy or resection and planned for standard of care biopsy or resection.

Recurrent Participants:

  • Recurrent craniopharyngioma, as based on histologic confirmation at time of initial diagnosis (participants will be eligible regardless of craniopharyngioma subtype; if papillary subtype, clinical trial assignment will be to the exploratory cohort).
  • Participants must be willing to provide adequate tissue. A minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required. Participants who do not meet this criteria may be discussed on a case-by-case basis with the Study Chairs."
  • Participants should be surgical candidates for biopsy or resection. If participants are not surgical candidates, but have available archival tumor tissue, participants will be enrolled into the exploratory cohort.
  • Participants can have been previously treated with surgical resection alone, radiation therapy, other systemic therapies, or any combination thereof.
  • Prior Therapy:
    • Had their last dose of myelosuppressive chemotherapy >= 21 days prior to study registration (>=42 days if nitrosourea therapy).
    • Had their last dose of hematopoietic growth factor >=14 days (long-acting growth factor) or >=7 days (short-acting growth factor) prior to study registration, or beyond the time during which adverse events (AEs) are known to occur.
    • Had their last dose of biologic (anti-neoplastic agent) >=7 days prior to study registration, or beyond the time during which AEs are known to occur.
    • Had their last dose of monoclonal antibodies >=21 days prior to study registration.


  • Had their last fraction of local irradiation to primary tumor ≥12 weeks prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.
  • At least 14 days after local palliative radiation (small-port).

All Participants:

  • Age 1 to 39 years.
  • Participants continuing on maintenance therapy after standard of care biopsy/resection must have measurable disease, as defined as lesions that can be accurately measured in two dimensions (longest diameter to be recorded) with a minimum size of no less than double the slice thickness. Previously irradiated lesions are considered non-measurable except in cases of documented progression of the lesion since the completion of radiation therapy. Participants without measurable disease may continue on study and will be followed for study endpoints, but will not be included as part of target accrual.
  • Performance Score: Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants <= 16 years of age. Participants 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.
  • Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration. The patient steroid dose should be no more than a steroid-equivalent of dexamethasone 0.1 mg/kg/day (or maximum 4mg/day; whichever is the lower dose) at time of enrollment. Participants receiving hormone replacement for hypopituitarism should be discussed with study chairs.
  • Organ Function Requirements:
    • Adequate Bone Marrow Function defined as:

      - Peripheral absolute neutrophil count (ANC) >=1000/mm3. - Platelet count >= 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).

    • Adequate Renal Function defined as Creatinine clearance or radioisotope Glomerular filtration rate (GFR) >= 70 mL/min/1.73 m2 or a serum creatinine based on age/gender as follows:

      - Age 1 - 2 years: Maximum Serum Creatinine (mg/dL) Male 0.6, Female 0.6. - Age 2 < 6 years: Maximum Serum Creatinine (mg/dL) Male 0.8, Female 0.8. - Age 6 < 10 years: Maximum Serum Creatinine (mg/dL) Male 1, Female 1. - Age 10 < 13 years: Maximum Serum Creatinine (mg/dL) Male 1.2, Female 1.2. - Age 13 < 16 years: Maximum Serum Creatinine (mg/dL) Male 1.5, Female 1.4. - Age >=16 years: Maximum Serum Creatinine (mg/dL) Male 1.7, Female 1.4. NOTE: The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Controls (CDC).

    • Adequate Liver Function defined as-

      - Bilirubin (sum of conjugated + unconjugated) <= 1.5 x upper limit of normal (ULN) for age (except in patients with documented Gilbert syndrome). - Serum glutamic-pyruvic transaminase (SGPT)((alanine aminotransferase (ALT)) <= 3 x ULN. - Serum albumin >=2 g/dL (20g/L).

    • Adequate Neurologic Function defined as participants with seizure disorder may be enrolled if well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.
    • Adequate Pancreatic Function defined as serum lipase <= 1.5 x ULN at baseline.
    • Adequate Pulmonary Function defined as no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry of > 92% while breathing room air.
  • The effects of DAY101 and nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 6 months after completion of DAY101 and/or nivolumab administration, whichever is later. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.

You CAN'T join if...

Newly Diagnosed Participants:

  • Participants should not have undergone any previous tumor-directed therapy.

Recurrent Participants:

  • Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from acute adverse events due to agents administered more than 4 weeks earlier.
  • Participants must be at least 1 week since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 1 week after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs.
  • Participants should not have previously received any RAS-pathway directed therapy combined with PD-1 inhibition. However, individual therapy with either of these individual agents will be allowed. Such subjects should be discussed with study chairs.

All Participants:

  • Rapidly progressive symptoms that require urgent surgery or radiation therapy, which would prevent central review and or preclude participation with tumor-directed medical management alone.
  • Uncontrolled symptoms of neuroendocrine dysfunction such as diabetes insipidus, hypothyroidism, panhypopituitarism (participants can be on supplemental medications for hormonal repletion; however, should be on controlled doses for at least 2 weeks prior to enrollment).
  • Patients with a history or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO), or ophthalmopathy present at baseline who would be considered a risk factor for CSR or RVO. Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor, or strabismus) will NOT be considered a significant abnormality for the purposes of this study.
  • Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to registration, ongoing cardiomyopathy, or current prolonged QT interval corrected for heart rate by Fridericia's formula (QTcF) interval > 440 ms based on triplicate ECG average.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to DAY101 or nivolumab or other agents used in study.
  • History of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens Johnsons syndrome (SJS), or hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of the investigational medicinal product.
  • History of pneumonitis within the last 5 years or history of thoracic radiation, including prior craniospinal irradiation (CSI) or have radiation fields that overlap the lung.
  • Nausea and vomiting >= Grade 2, malabsorption requiring supplementation, or significant bowel or stomach resection that would preclude adequate absorption.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
  • Participants who are receiving any other investigational agents.
  • Participants who have received a live / attenuated vaccine within 30 days of registration.
  • Participants with a known disorder that affects their immune system, such as HIV or Hepatitis B or C, an auto-immune disorder disease that has 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. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids are not necessarily excluded from the study but need to be discussed with the study chair.
  • Participants with a ≥ Grade 2 hypothyroidism due to history of autoimmunity are not eligible. (Note: Hypothyroidism due to previous irradiation or thyroidectomy will not impact eligibility).
  • Participants who have received prior solid organ or bone marrow transplantation are not eligible.
  • Women of childbearing potential must not be pregnant or breast-feeding.
  • Current treatment with a strong cytochrome P4502C8(CYP2C8) inhibitor or inducer other than those allowed per Section 5.6.1. Medications that are substrates of CYP2C8 are allowed but should be used with caution.
  • Participants with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.


  • UCSF accepting new patients
    San Francisco California 94143 United States
  • Rady Children's Hospital/University of California, San Diego accepting new patients
    San Diego California 92037 United States

Lead Scientist at UCSF


accepting new patients
Start Date
Completion Date
Sabine Mueller, MD, PhD
Phase 2 Craniopharyngioma Research Study
Study Type
Expecting 56 study participants
Last Updated