The only two trials stopped on a stated risk-benefit judgement are GSK2879552 (LSD1) studies in AML, while iadademstat, another LSD1 inhibitor, ran a KMT2A-rearranged-enriched expansion with an acceptable safety profile - so the stop looks molecule-specific, and its reason is unread
also called GSK2879552 risk benefit · LSD1 inhibitor trial stops
Two early trials of one leukaemia drug that blocks the enzyme LSD1 were closed because the balance of benefit and risk did not favour continuing. A different LSD1 drug went on to treat people with KMT2A-rearranged leukaemia, so the problem was probably that molecule, but the reason was not written down in the registry.
The same thing, for a scientist
Registry strings, verbatim: 'The risk benefit in relapsed refractory AML does not favor continuation of the study.' (n = 41) and 'The risk benefit in the study population does not favor continuation of the study' (n = 7); neither says whether the judgement was about toxicity, lack of activity or both. Counter-example: iadademstat phase I, 27 dose-escalation patients plus a 14-patient expansion enriched for KMT2A-rearranged AML, reported as having a good safety profile. A published GSK2879552 phase I letter exists (Leuk Lymphoma 2022, PMID 34927529) but carries no PubMed abstract and was not read.
What is and is not known
Known: two GSK2879552 trials ended on a risk-benefit judgement. Not known: whether that judgement was toxicity, absence of efficacy or both. The published phase I letter would say, but its PubMed record has no abstract and I did not obtain the full text. An earlier search through a different tool returned only a review and would have led to the false conclusion that no clinical report exists.
| script | analyses/q200-how-neighbouring-epigenetic-drug-classes-stopped-in-acute-leukaemia/classify.py |
|---|
gsk2879552 stops
[
{
"category": "risk-benefit",
"class": "LSD1",
"why_stopped": "The risk benefit in relapsed refractory AML does not favor continuation of the study.",
"enrollment": 41,
"status": "TERMINATED",
"title": "A Phase I Dose Escalation Study of GSK2879552 in Subjects With Acute Myeloid Leukemia (AML)"
},
{
"category": "risk-benefit",
"class": "LSD1",
"why_stopped": "The risk benefit in the study population does not favor continuation of the study",
"enrollment": 7,
"status": "TERMINATED",
"title": "Safety, Clinical Activity, Pharmacokinetics (PK) and Pharmacodynamics Study of GSK2879552, Alone or With Azacitidine, in Subjects With High Risk Myelodysplastic Syndromes (MDS)"
}
]- This corpus carries LSD1 inhibition as a candidate partner for menin inhibition in KMT2A-rearranged leukaemia. One LSD1 molecule has two stops on an unexplained risk-benefit judgement, so do not assume class-wide acceptability for a new LSD1 combination, especially in infants.
- What do the GSK2879552 phase I letter and the full registry results say the risk-benefit judgement was about?
- Is iadademstat now in trials combining it with menin inhibitors in KMT2A-rearranged disease, and what dose-limiting events have been seen?
- E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
Two GSK2879552 (LSD1 inhibitor) trials in relapsed or refractory AML were stopped with the statement that the risk-benefit 'does not favor continuation': NCT02177812 (n = 41, started 2014-08) and NCT02929498 (n = 7, started 2017-07).
ClinicalTrials.gov API v2 (raw, so whyStopped is present), pulled 2026-10-06 by analyses/q200-how-neighbouring-epigenetic-drug-classes-stopped-in-acute-leukaemia/pull.py · ClinicalTrials.gov 2026What this evidence cannot show
Both strings read in full; they are the only two of 21 stopped trials across five classes whose stated reason is a risk-benefit judgement.
Evidence that argues against this (1)
- 'Risk-benefit' combines toxicity and activity, and the registry does not separate them, so it cannot be read as a safety stop. The molecule had no KMT2A-rearranged enrichment in the registry record, which limits what it says about KMT2A-rearranged disease. ClinicalTrials.gov 2026
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In the iadademstat (ORY-1001) first-in-human phase I in relapsed or refractory AML, 27 patients were treated in dose escalation and 14 in an expansion cohort enriched for MLL/KMT2A-rearranged AML; most adverse events were those expected in relapsed AML, the authors report a good safety profile, and blast differentiation was seen in patients with MLL translocations.
First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia · J Clin Oncol 2020What this evidence cannot show
Read from the raw PubMed XML abstract 2026-10-06.
Evidence that argues against this (1)
- Iadademstat is a different molecule from GSK2879552, tested in a different population and at different doses, so its acceptability does not clear the first molecule. A phase I safety statement is the authors' summary of a small trial and is not a tolerability guarantee at the doses and combinations used later. J Clin Oncol 2020
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
A published phase I report of GSK2879552 as mono- and combination therapy in relapsed or refractory AML or high-risk MDS exists (Leuk Lymphoma 2022, PMID 34927529), but its PubMed record is a Letter with no abstract, so its safety and efficacy findings are not read here.
What this evidence cannot show
Existence, title, DOI and publication type were read from the raw PubMed XML on 2026-10-06; the record carries no abstract element. This is a pointer for the next reader, not a result.
Evidence that argues against this (1)
- Citing a paper I could not read for its findings would be a claim without support; this item asserts only that it exists and where to look. Leuk Lymphoma 2022
GSK2879552 and iadademstat
LSD1 inhibitor trial stops