Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax

1. Is the biology right?

• Somatic driver evidence: no · None of BCL2, BCL2L1, BCL2L2, ABL1, BCR has somatic-mutation evidence in childhood acute lymphoblastic leukemia

  Rule: Open Targets has somatic-mutation evidence for the target in this cancer. Source: Open Targets: BCL2 in childhood acute lymphoblastic leukemia, 2026-11-11
• Human genetic evidence: no · No germline or somatic evidence for BCL2, BCL2L1, BCL2L2, ABL1, BCR in childhood acute lymphoblastic 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: BCL2 in childhood acute lymphoblastic leukemia, 2026-11-11
• Pediatric target: yes · ABL1 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 NCT05192889, 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: Vincristine, Cytarabine, Methotrexate, Cyclophosphamide, Etoposide, Leucovorin: standard agents, not counted in these flags.
• BCL2 (via Venetoclax): Open Targets has no association between BCL2 and childhood acute lymphoblastic leukemia. · Open Targets: BCL2 in childhood acute lymphoblastic leukemia
• BCL2L1 (via Navitoclax): Open Targets has no association between BCL2L1 and childhood acute lymphoblastic leukemia. · Open Targets: BCL2L1 in childhood acute lymphoblastic leukemia
• BCL2L2 (via Navitoclax): Open Targets has no association between BCL2L2 and childhood acute lymphoblastic leukemia. · Open Targets: BCL2L2 in childhood acute lymphoblastic leukemia
• ABL1 (via Dasatinib): Open Targets has no association between ABL1 and childhood acute lymphoblastic leukemia. · Open Targets: ABL1 in childhood acute lymphoblastic leukemia
• BCR (via Dasatinib): Open Targets has no association between BCR and childhood acute lymphoblastic leukemia. · Open Targets: BCR in childhood acute lymphoblastic 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: no · Non-randomised

  Rule: Registry allocation field. Source: ClinicalTrials.gov NCT05192889, 2026-11-11
• Small denominator: no · 35 enrolled; each patient moves a rate by 100 ÷ 35 = 2.9 points

  Rule: Enrolment under 30; the arithmetic is shown, not a benchmark. Source: ClinicalTrials.gov NCT05192889, 2026-11-11
• Primary endpoint is overall survival: no · Number of Participants With Minimal Residual Disease (MRD)-Negative Response; Recommended Phase 2 Dose of Venetoclax in Combination With a) High-dose Cytarabine and Navitoclax; Recommended Phase 2 Dose of Venetoclax in Combination With b) Blinatumomab

  Rule: A registered primary outcome measure names overall survival. Source: ClinicalTrials.gov NCT05192889, 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 2025-09-22

  Rule: Primary completion (actual) more than 12 months ago and no results posted to the registry. Source: ClinicalTrials.gov NCT05192889, 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: 147 terminated, withdrawn or suspended trials of drugs against BCL2; 9 give no reason. Reasons are quoted as the registry gives them on the target page. · BCL2: 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 2 sites in United States

  Rule: All listed sites are in one country; the share of US sites is shown. Source: ClinicalTrials.gov NCT05192889, 2026-11-11
• EU paediatric investigation plan: yes · EMA/PE/0000182075 (venetoclax, Treatment of malignant neoplasms of the haematopoietic and lymphoid tissue;Treatment of solid malignant tumours): PM: decision on the application for modification of an agreed PIP, 3 Jan 2025; EMEA-000478-PIP02-18 (navitoclax, Treatment of myelofibrosis): W: decision granting a waiver in all age groups for all conditions or indications, 14 Aug 2018; EMEA-000567-PIP01-09-M05 (dasatinib, Treatment of Philadelphia-chromosome (BCR-ABL translocation)-positive acute lymphoblastic leukaemia;Treatment of Philadelphia-chromosome (BCR-ABL translocation)-positive chronic myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 16 Feb 2018; compliance positive 23 Feb 2018

  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/3/26/3246 positive 22 Jun 2026: Treatment of Diamond-Blackfan anaemia; EU/3/19/2233 withdrawn 16 Dec 2019: Treatment of myelofibrosis; EU/3/17/1954 withdrawn 12 Dec 2017: Treatment of mantle cell lymphoma; EU/3/16/1766 withdrawn 14 Oct 2016: Treatment of diffuse large B-cell lymphoma; +5 more

  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 · Sprycel: authorised since 20 Nov 2006; Venclyxto: authorised since 4 Dec 2016; Dasatinib Accord Healthcare: authorised since 26 Jul 2024; Dasatinib Accord: withdrawn since 24 Mar 2022; +1 more

  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 · Calaspargase pegol - mknl [Asparlas], 20 Dec 2018: As a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia in pediatric and young adult patients age 1 month to 21 years; Dasatinib [Sprycel], 21 Dec 2018: Treatment of pediatric patients 1 year of age and older with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy; Dasatinib [Sprycel], 9 Nov 2017: Treatment of pediatric patients 1 year of age and older with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase

  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 · 180 interventional studies of Venetoclax, Navitoclax, Calaspargase Pegol, Dasatinib include patients under 18; 106 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: St. Jude Children's Research Hospital (academic or other) · ClinicalTrials.gov NCT05192889
• principal investigator: Seth E. Karol, MD, St. Jude Children's Research Hospital · 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.