I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients

1. Is the biology right?

• Somatic driver evidence: no · None of ABL1, PDGFRB, KIT, CCR5, CCR2, BDKRB2 has somatic-mutation evidence in COVID-19

  Rule: Open Targets has somatic-mutation evidence for the target in this cancer. Source: Open Targets: ABL1 in COVID-19, 2026-11-11
• Human genetic evidence: yes · CCR5: germline; CCR2: germline

  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: CCR5 in COVID-19, 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, PDGFRB, KIT 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 NCT04488081, 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 Imatinib Mesylate): Evidence types in COVID-19: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: ABL1 in COVID-19
• PDGFRB (via Imatinib Mesylate): Evidence types in COVID-19: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: PDGFRB in COVID-19
• KIT (via Imatinib Mesylate): Evidence types in COVID-19: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: KIT in COVID-19
• CCR5 (via Cenicriviroc): Evidence types in COVID-19: literature, genetic_association, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, gwas_credible_sets, europepmc. · Open Targets: CCR5 in COVID-19
• CCR2 (via Cenicriviroc): Evidence types in COVID-19: literature, genetic_association, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, gwas_credible_sets, europepmc. · Open Targets: CCR2 in COVID-19
• BDKRB2 (via Icatibant): Evidence types in COVID-19: literature, clinical; literature listed separately from human genetics. Datasources: clinical_precedence, europepmc. · Open Targets: BDKRB2 in COVID-19

• 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 NCT04488081, 2026-11-11
• Small denominator: no · 1500 planned; each patient moves a rate by 100 ÷ 1500 = 0.1 points

  Rule: Enrolment under 30; the arithmetic is shown, not a benchmark. Source: ClinicalTrials.gov NCT04488081, 2026-11-11
• Primary endpoint is overall survival: no · Identify agents that will result in substantial improvements to the clinical condition of participants with COVID-19.

  Rule: A registered primary outcome measure names overall survival. Source: ClinicalTrials.gov NCT04488081, 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 2028-07-31; not yet due

  Rule: Primary completion (actual) more than 12 months ago and no results posted to the registry. Source: ClinicalTrials.gov NCT04488081, 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 36 sites in United States

  Rule: All listed sites are in one country; the share of US sites is shown. Source: ClinicalTrials.gov NCT04488081, 2026-11-11
• EU paediatric investigation plan: yes · EMEA-002826-PIP01-20-M04 (remdesivir, Treatment of Coronavirus disease 2019 (COVID-19)): PM: decision on the application for modification of an agreed PIP, 27 Oct 2023; compliance positive 15 Dec 2023; EMEA-002643-PIP01-19-M01 (imatinib, Treatment of acute lymphoblastic leukaemia;Treatment of chronic myeloid leukaemia): PM: decision on the application for modification of an agreed PIP, 29 Oct 2021; EMEA-001999-PIP02-17-M01 (cenicriviroc, Treatment of non-alcoholic steatohepatitis (NASH)): PM: decision on the application for modification of an agreed PIP, 9 Sept 2020; EMEA-000408-PIP01-08-M05 (icatibant acetate, Treatment of hereditary angioedema): PM: decision on the application for modification of an agreed PIP, 30 Oct 2015; compliance positive 19 Aug 2016; +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/3/21/2449 positive 21 Jun 2021: Treatment of pulmonary arterial hypertension; EU/3/14/1357 positive 19 Nov 2014: Treatment of acute respiratory distress syndrome (ARDS); EU/3/03/133 expired 18 Feb 2003: Treatment of angioedema; EU/3/16/1615 positive 17 Feb 2016: Treatment of Ebola virus disease; +7 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 · Glivec: authorised since 7 Nov 2001; Firazyr: authorised since 11 Jul 2008; Imatinib Accord: authorised since 30 Jun 2013; Icatibant Accord: authorised since 16 Jul 2021; +7 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 · Imatinib Mesylate [Gleevec] &, 25 Jan 2013: Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy; Imatinib Mesylate [Gleevec] &, 27 Sept 2006: Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ 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 · 154 interventional studies of Remdesivir, Imatinib Mesylate, Cenicriviroc, Icatibant include patients under 18; 18 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: QuantumLeap Healthcare Collaborative (academic or other) · ClinicalTrials.gov NCT04488081
• principal investigator: Derek W Russell, MD, University of Alabama at Birmingham Heersink School of Medicine · Person page
• principal investigator: Kathleen D Liu, MD, University of California, San Francisco · Person page
• principal investigator: Laura Esserman, MD, University of California, San Francisco · 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.