57 Participants Needed

Nivolumab + DAY101 for Craniopharyngioma

(PNOC029 Trial)

Recruiting at 15 trial locations
CJ
PO
Overseen ByPNOC Operations Office
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

The current study assesses the tolerability and efficacy of monotherapy with pan-RAF-kinase (Tovorafenib) inhibition for the treatment of children and young adults with craniopharyngioma.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, participants must not have had chemotherapy or radiotherapy within 3 weeks prior to entering the study, and certain medications may need to be discussed with the study chairs. It's best to consult with the trial coordinators about your specific medications.

How is the drug combination of Nivolumab and DAY101 unique for treating craniopharyngioma?

The combination of Nivolumab and DAY101 is unique because Nivolumab is an immunotherapy drug that helps the immune system attack cancer cells, and DAY101 is a targeted therapy that inhibits specific proteins involved in tumor growth. This combination may offer a novel approach for craniopharyngioma, a condition with limited standard treatment options.12345

What data supports the effectiveness of the drug combination Nivolumab and DAY101 for treating craniopharyngioma?

Research shows that papillary craniopharyngiomas with BRAF V600E mutations respond well to BRAF/MEK inhibitors, and both craniopharyngioma types express PD-L1, suggesting potential effectiveness of immune checkpoint inhibitors like Nivolumab.678910

Who Is on the Research Team?

Dr. Sabine Mueller | UCSF Benioff ...

Sabine Mueller, MD, PhD, MAS

Principal Investigator

University of California, San Francisco

CK

Cassie Kline, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to 39 with craniopharyngioma, who can undergo surgery. They should not have had certain treatments recently, must be able to provide tissue samples, and have good organ function. Pregnant or breastfeeding women are excluded, as well as those with immune disorders or severe cardiovascular issues.

Inclusion Criteria

I still have visible signs of my disease while on maintenance therapy.
Participants must agree to use adequate contraception if of child-bearing potential
I have been newly diagnosed with craniopharyngioma based on imaging.
See 6 more

Exclusion Criteria

Participants with a history of allergic reactions to study drugs or compounds with similar composition are excluded
I have not received any treatment for my cancer yet.
I do not have unmanaged symptoms from neuroendocrine issues.
See 10 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive one dose of nivolumab and/or Tovorafenib prior to planned biopsy or resection

2 weeks
1 visit (in-person)

Combination Maintenance Therapy

Participants continue on combination maintenance therapy of nivolumab every 2 weeks and Tovorafenib once weekly

Up to 24 months
Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

  • DAY101
  • Nivolumab
Trial Overview The study tests the safety and effectiveness of combining Nivolumab (a PD-1 inhibitor) with DAY101 (a pan-RAF kinase inhibitor) in treating craniopharyngioma. It's designed for patients who may be newly diagnosed or have recurrent disease after prior treatments.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: Group 2, Arm B: Non-biopsy/resection participantsExperimental Treatment1 Intervention
Group II: Group 2, Arm A: Neoadjuvant TovorafenibExperimental Treatment1 Intervention
Group III: Group 1: Neoadjuvant TovorafenibExperimental Treatment1 Intervention

DAY101 is already approved in United States for the following indications:

🇺🇸
Approved in United States as Ojemda for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Sabine Mueller, MD, PhD

Lead Sponsor

Trials
9
Recruited
440+

Day One Biopharmaceuticals, Inc.

Industry Sponsor

Trials
8
Recruited
1,100+

Bristol-Myers Squibb

Industry Sponsor

Trials
2,731
Recruited
4,127,000+
Headquarters
New York City, USA
Known For
Oncology & Cardiovascular
Top Products
Eliquis, Opdivo, Revlimid, Orencia
Christopher Boerner profile image

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt profile image

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a study of 52 craniopharyngioma cases, adamantinomatous craniopharyngiomas (ACPs) were found to express PD-1 and showed aberrant β-catenin activity, while papillary craniopharyngiomas (PCPs) predominantly had BRAF mutations, indicating distinct molecular profiles that could guide treatment strategies.
Both ACPs and PCPs exhibited high levels of PD-L1 expression, suggesting potential for immunotherapy; however, there was no significant difference in clinical outcomes between the two variants, highlighting the need for personalized approaches in managing these tumors.
Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).Moreno-Torres, B., Campos-Martín, Y., Meléndez, B., et al.[2022]
Vemurafenib combined with cobimetinib has shown effectiveness in treating patients with BRAF-mutant papillary craniopharyngioma, a type of brain tumor.
This combination therapy targets specific mutations, suggesting a tailored approach to treatment that could improve outcomes for affected patients.
BRAF-MEK Inhibition Is Effective in BRAFV600E-Mutant Papillary Craniopharyngioma.[2023]
Both adamantinomatous (ACP) and papillary craniopharyngiomas (PCP) express PD-L1, with ACP showing PD-L1 in the cyst lining and intrinsic PD-1 in certain tumor cells, suggesting a potential target for immunotherapy.
The study indicates that targeting the PD-1/PD-L1 immune checkpoint pathway could be a promising therapeutic strategy for both ACP and PCP, as both subtypes exhibit characteristics that may respond to such treatments.
Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma.Coy, S., Rashid, R., Lin, JR., et al.[2019]

Citations

Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid). [2022]
BRAF-MEK Inhibition Is Effective in BRAFV600E-Mutant Papillary Craniopharyngioma. [2023]
Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma. [2019]
Treatment and outcome of the Dutch Childhood Craniopharyngioma Cohort study: First results after centralization of care. [2023]
Case report and literature review of BRAF-V600 inhibitors for treatment of papillary craniopharyngiomas: A potential treatment paradigm shift. [2022]
Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials. [2020]
JAVELIN Head and Neck 100: a Phase III trial of avelumab and chemoradiation for locally advanced head and neck cancer. [2020]
Nivolumab versus investigator's choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety in CheckMate 141 by age. [2020]
Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). [2022]
Protocol for the EACH trial: a multicentre phase II study evaluating the safety and antitumour activity of the combination of avelumab, an anti-PD-L1 agent, and cetuximab, as any line treatment for patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC) in the UK. [2023]
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