Study to Evaluate the Reinduction and Second Stop of TKI With Ponatinib in CML in Molecular Response (ResToP)

1. Is the biology right?

• Somatic driver evidence: yes · ABL1, BCR in chronic myeloid leukemia

  Rule: Open Targets has somatic-mutation evidence for the target in this cancer. Source: Open Targets: ABL1 in chronic myeloid leukemia, 2026-11-11

  Published context: 2.3× relative success for targets with somatic (IntOGen) support in oncology (Minikel et al., Nature 2024, drug programs to 2023). A ratio between groups, not a probability for this program; mostly phase 2 to 3.
• Human genetic evidence: yes · ABL1: curated genetic literature, germline, somatic; BCR: curated genetic literature, germline, somatic

  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: ABL1 in chronic myeloid leukemia, 2026-11-11

  Published context: 2.6× relative probability of success, phase 1 to launch, with human genetic support (Minikel et al., Nature 2024, drug programs to 2023). All therapy areas, mostly germline evidence; not a probability for this program.
• 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 NCT04160546, 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.

• ABL1 (via Ponatinib): Evidence types in chronic myeloid leukemia: clinical, genetic_literature, affected_pathway, literature, genetic_association, somatic_mutation, animal_model; literature and animal_model listed separately from human genetics. Datasources: clinical_precedence, eva, cancer_gene_census, uniprot_literature, eva_somatic, cancer_biomarkers, europepmc, impc. · Open Targets: ABL1 in chronic myeloid leukemia
• BCR (via Ponatinib): Evidence types in chronic myeloid leukemia: clinical, genetic_literature, affected_pathway, literature, genetic_association, somatic_mutation; literature listed separately from human genetics. Datasources: clinical_precedence, reactome, cancer_gene_census, uniprot_literature, eva, europepmc. · Open Targets: BCR in chronic myeloid leukemia
• PTGS2 (via Acetylsalicylic acid): Evidence types in chronic myeloid leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: PTGS2 in chronic myeloid leukemia
• PTGS1 (via Acetylsalicylic acid): Evidence types in chronic myeloid leukemia: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: PTGS1 in chronic 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: no · Single group

  Rule: Registry allocation field. Source: ClinicalTrials.gov NCT04160546, 2026-11-11
• Small denominator: no · 34 enrolled; each patient moves a rate by 100 ÷ 34 = 2.9 points

  Rule: Enrolment under 30; the arithmetic is shown, not a benchmark. Source: ClinicalTrials.gov NCT04160546, 2026-11-11
• Primary endpoint is overall survival: no · Proportion of patients with a maintained MMR within 52 weeks following ponatinib Treatment-Free Remission (TFR)

  Rule: A registered primary outcome measure names overall survival. Source: ClinicalTrials.gov NCT04160546, 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 2025-12-31, 10 months ago; within 12 months

  Rule: Primary completion (actual) more than 12 months ago and no results posted to the registry. Source: ClinicalTrials.gov NCT04160546, 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: 300 terminated, withdrawn or suspended trials of drugs against ABL1; 16 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page. · ABL1: 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 13 sites in Spain

  Rule: All listed sites are in one country; the share of US sites is shown. Source: ClinicalTrials.gov NCT04160546, 2026-11-11
• EU paediatric investigation plan: yes · EMA/PE/0000238858 (acetylsalicylic acid;rivaroxaban, Prevention of atherothrombotic events): W: decision granting a waiver in all age groups for all conditions or indications, 16 Apr 2025; EMA/PE/0000261034 (ponatinib, Treatment of chronic myeloid leukaemia;Treatment of Philadelphia chromosome positive acute lymphoblastic leukaemia): PM: decision on the application for modification of an agreed PIP, 28 Apr 2025; EMEA-003410-PIP01-23 (acetylsalicylic acid;rosuvastatin calcium, Prevention of cardiovascular events): W: decision granting a waiver in all age groups for all conditions or indications, 14 Jul 2023; EMEA-002239-PIP02-21 (acetylsalicylic acid;rosuvastatin calcium, Prevention of cardiovascular events): W: decision granting a waiver in all age groups for all conditions or indications, 31 Jan 2022; +23 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/3/04/208 withdrawn 29 Jul 2004: Treatment of polycythaemia vera; EU/3/09/715 expired 2 Feb 2010: Treatment of acute lymphoblastic leukaemia; EU/3/09/716 expired 2 Feb 2010: Treatment of chronic myeloid leukaemia; EU/3/14/1421 withdrawn 15 Jan 2015: Treatment of gastrointestinal stromal tumours

  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 · DuoPlavin: authorised since 14 Mar 2010; Iclusig: authorised since 1 Jul 2013; Clopidogrel / Acetylsalicylic acid Viatris (previously Clopidogrel / Acetylsalicylic acid Mylan): authorised since 9 Jan 2020; Clopidogrel/Acetylsalicylic acid Zentiva (previously DuoCover): authorised since 14 Mar 2010; +3 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: no · FDA's table lists no pediatric approval of Ponatinib, Acetylsalicylic acid

  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 · 133 interventional studies of Ponatinib, Acetylsalicylic acid include patients under 18; 34 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.
• Cited case: In February 2022 FDA asked its Oncologic Drugs Advisory Committee whether sintilimab's application, resting on ORIENT-11, a phase 3 run only in China, needed further trials showing it applies to US patients and US practice. One case, not a rule. · FDA, ODAC 10 Feb 2022, draft questions
• 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: Fundacion CRIS de Investigación para Vencer el Cáncer (academic or other) · ClinicalTrials.gov NCT04160546
• principal investigator: Joaquín Martínez López, MD, Hospital Universitario 12 de Octubre · Person page
• principal investigator: Valentín García Gutierrez, MD, Hospital Universitario Ramon y Cajal · Person page
• principal investigator: Juan Carlos Hernández Boluda, MD, Hospital Clínico de Valencia · 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.