A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations

1. Is the biology right?

• Somatic driver evidence: no · None of TOP2A, TOP2B, CD33 has somatic-mutation evidence in acute myeloid leukemia

  Rule: Open Targets has somatic-mutation evidence for the target in this cancer. Source: Open Targets: TOP2A in acute myeloid leukemia, 2026-11-11
• Human genetic evidence: no · No germline or somatic evidence for TOP2A, TOP2B, CD33 in acute myeloid leukemia

  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: TOP2A in acute myeloid leukemia, 2026-11-11
• Pediatric target: yes · CD33 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: yes · Haematologic

  Rule: From the indication, or the registry conditions when no indication matches. Source: ClinicalTrials.gov NCT04293562, 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.

• Background therapy: Cytarabine, Etoposide, Methotrexate: standard agents, not counted in these flags.
• TOP2A (via Daunorubicin Hydrochloride): Evidence types in acute myeloid leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: TOP2A in acute myeloid leukemia
• TOP2B (via Dexrazoxane Hydrochloride): Evidence types in acute myeloid leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: TOP2B in acute myeloid leukemia
• CD33 (via Gemtuzumab Ozogamicin): Evidence types in acute myeloid leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: CD33 in acute myeloid leukemia

• 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: yes · Randomised allocation

  Rule: Registry allocation field. Source: ClinicalTrials.gov NCT04293562, 2026-11-11
• Small denominator: no · 1400 planned; each patient moves a rate by 100 ÷ 1400 = 0.1 points

  Rule: Enrolment under 30; the arithmetic is shown, not a benchmark. Source: ClinicalTrials.gov NCT04293562, 2026-11-11
• Primary endpoint is overall survival: no · Event-free survival (EFS)

  Rule: A registered primary outcome measure names overall survival. Source: ClinicalTrials.gov NCT04293562, 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 · Primary completion expected 2029-06-30; not yet due

  Rule: Primary completion (actual) more than 12 months ago and no results posted to the registry. Source: ClinicalTrials.gov NCT04293562, 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: 728 terminated, withdrawn or suspended trials of drugs against TOP2A; 3 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page. · TOP2A: 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: no · 206 sites in 4 countries; 186 in the United States (90%)

  Rule: All listed sites are in one country; the share of US sites is shown. Source: ClinicalTrials.gov NCT04293562, 2026-11-11
• EU paediatric investigation plan: yes · EMEA-001858-PIP02-16-M04 (daunorubicin;cytarabine, Treatment of acute myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 25 Oct 2024; EMEA-001733-PIP02-15-M03 (gemtuzumab ozogamicin, Treatment of acute myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 13 Sept 2024

  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/3/01/059 expired 19 Sept 2001: Treatment of anthracycline extravasations; EU/3/11/942 positive 11 Jan 2012: Treatment of acute myeloid leukaemia; EU/3/00/005 positive 18 Oct 2000: Treatment of acute myeloid leukaemia; EU/3/08/585 positive 3 Dec 2008: Treatment of acute myeloid leukaemia

  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 data download (dated snapshot), 2026-11-11
• Authorised in the EU: yes · Mylotarg: authorised since 19 Apr 2018, orphan medicine; Vyxeos liposomal (previously Vyxeos): authorised since 23 Aug 2018, orphan medicine; Savene: authorised since 27 Jul 2006; Mylotarg: refused, orphan medicine

  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 · Asparaginase Erwinia chrysanthemi (recombinant)-rywn [Rylaze], 30 Jun 2021: As a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase; Asparaginase Erwinia Chrysanthemi [Erwinaze] [currently in shortage], 18 Nov 2011: A component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase; Daunorubicin Hydrochloride, 19 Dec 1979: In combination with other approved anticancer drugs, for remission induction in acute lymphocytic leukemia of children and adults; +2 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 · 705 interventional studies of Asparaginase Erwinia chrysanthemi, Daunorubicin Hydrochloride, Dexrazoxane Hydrochloride, Gemtuzumab Ozogamicin include patients under 18; 136 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: Children's Oncology Group (academic or other) · ClinicalTrials.gov NCT04293562
• principal investigator: Todd M Cooper, Children's Oncology Group · 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.