Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers

1. Is the biology right?

• Somatic driver evidence: no · None of PDCD1 has somatic-mutation evidence in medulloblastoma

  Rule: Open Targets has somatic-mutation evidence for the target in this cancer. Source: Open Targets: PDCD1 in medulloblastoma, 2026-11-11
• Human genetic evidence: no · No germline or somatic evidence for PDCD1 in medulloblastoma

  Rule: Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence. Source: Open Targets: PDCD1 in medulloblastoma, 2026-11-11
• Pediatric target: yes · PDCD1 on the FDA list

  Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study. Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
• Haematologic cancer: no · Solid tumour

  Rule: From the indication, or the registry conditions when no indication matches. Source: ClinicalTrials.gov NCT03173950, 2026-11-11

  Published context: Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid (BIO / Informa / QLS 2021, 2011–2020). Population-level, not a prediction.

• PDCD1 (via Nivolumab): Evidence types in medulloblastoma: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: PDCD1 in medulloblastoma

• Not loaded on this app yet: Normal-tissue expression in vital organs. Source: Human Protein Atlas (ticket 36).
• Not loaded on this app yet: Pan-essential in cell lines. Source: DepMap (ticket 36).
• Not loaded on this app yet: Approved drug on this target. Source: Drugs@FDA (ticket 30).

2. Can the result be trusted?

• Randomised: no · Single group

  Rule: Registry allocation field. Source: ClinicalTrials.gov NCT03173950, 2026-11-11
• Small denominator: no · 136 enrolled; each patient moves a rate by 100 ÷ 136 = 0.7 points

  Rule: Enrolment under 30; the arithmetic is shown, not a benchmark. Source: ClinicalTrials.gov NCT03173950, 2026-11-11
• Primary endpoint is overall survival: no · Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Meas…; Disease Control Rate (Complete Response (CR) + Partial Response (PR) or Durable Stable Disease (SD) for 6 Months Meas…; Progression Free Survival (PFS) (and 1 more)

  Rule: A registered primary outcome measure names overall survival. Source: ClinicalTrials.gov NCT03173950, 2026-11-11

  Published context: Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3 (Otsuka 2021, 400 phase 3 oncology trials, to 2020). Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival.

  Published context: 52% of surrogate-to-OS correlations are low (Prasad 2015, published to 2014). Shown with the figure above.
• Results overdue: no · Results posted 2026-08-18

  Rule: Primary completion (actual) more than 12 months ago and no results posted to the registry. Source: ClinicalTrials.gov NCT03173950, 2026-11-11

• Not loaded on this app yet: Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff. Source: Readout extraction (ticket 32).
• Not loaded on this app yet: Primary endpoint changed between registry versions. Source: Registry versions in the store (ticket 32).

3. What must it beat?

• Not loaded on this app yet: Control-arm result and approved therapies for the same segment, with label links. Source: Drugs@FDA, FDA labels and readouts (tickets 30, 32).

4. Too crowded, or too late?

• Stopped on this target: 688 terminated, withdrawn or suspended trials of drugs against PDCD1; 1 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page. · PDCD1: what already stopped

• Not loaded on this app yet: Programs on the target by phase and months behind the leader. Source: Programs and Drugs@FDA (ticket 33).

5. Can it be approved, and stay approved?

• Single-country: yes · All 3 sites in United States

  Rule: All listed sites are in one country; the share of US sites is shown. Source: ClinicalTrials.gov NCT03173950, 2026-11-11
• EU paediatric investigation plan: yes · EMEA-002727-PIP03-23 (nivolumab;relatlimab, Treatment of melanoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 6 May 2024; EMA/PE/0000232936 (atigotatug;nivolumab, Treatment of small cell lung cancer): W: decision granting a waiver in all age groups for all conditions or indications, 21 Mar 2025; EMEA-001407-PIP02-15-M07 (nivolumab, Treatment of malignant neoplasms of lymphoid tissue;Treatment of malignant neoplasms of the central nervous system): PM: decision on the application for modification of an agreed PIP, 6 May 2024; EMEA-002727-PIP02-23 (relatlimab;nivolumab, Treatment of all conditions included in the category of malignant neoplasms (except central nervous system tumours, hematopoietic and lymphoid tissue neoplasms and melanoma)): W: decision granting a waiver in all age groups for all conditions or indications, 1 Dec 2023; +3 more

  Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
• EU orphan designation: yes · EU/3/26/3215 positive 25 Mar 2026: Treatment of pulmonary neuroendocrine carcinoma

  Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA EU/3/26/3215, 2026-11-11
• Authorised in the EU: yes · Opdivo: authorised since 19 Jun 2015; Opdualag: authorised since 15 Sept 2022; Nivolumab BMS: withdrawn since 20 Jul 2015

  Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
• FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link

  Rule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
• FDA pediatric oncology approval: yes · Nivolumab and hyaluronidase-nvhy [Opdivo Quantig], 24 Nov 2025: Treatment of adult and pediatric patients 12 years and older who weigh 30 kg or greater with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) following treatment with intravenous nivolumab and ipilimumab combination therapy; Nivolumab and hyaluronidase-nvhy [Opdivo Quantig], 24 Nov 2025: Treatment of adult and pediatric patients 12 years and older who weigh 30 kg or greater, with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan; Nivolumab and hyaluronidase-nvhy [Opdivo Quantig], 24 Nov 2025: Adjuvant treatment of adult and pediatric patients 12 years and older who weigh 30 kg or greater with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma; +7 more

  Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
• Registered studies open to children: yes · 122 interventional studies of Nivolumab include patients under 18; 69 are recruiting, not yet recruiting or active

  Rule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11

• Caveat: Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality.
• Rare pediatric disease voucher: FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. · FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs

• Not loaded on this app yet: Precedent approvals for target, modality and endpoint; accelerated-approval status. Source: Drugs@FDA and FDA accelerated-approval tables (ticket 30).

6. Can the sponsor finish?

• Sponsor: National Cancer Institute (NCI) (academic or other) · ClinicalTrials.gov NCT03173950
• principal investigator: Kevin Camphausen, M.D., National Cancer Institute (NCI) · Person page

• Not loaded on this app yet: Filed cash, quarterly spend and the runway arithmetic. Source: SEC XBRL company facts (ticket 37).
• Not loaded on this app yet: Sponsor's completed vs stopped oncology trials and results-reporting record. Source: Registry, by company (ticket 37).

What public data cannot tell you

Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.