A documented absence: not one endocrine outcome measure across the three lead menin-inhibitor trials
also called menin trial endpoint audit · endocrine endpoint gap · AUGMENT-101 KOMET-001 cAMeLot-1 endpoints
We read every registered outcome measure and eligibility criterion for the three main menin-inhibitor trials. Not one of them collects calcium, parathyroid hormone, growth or any other hormone measurement, even though two of the trials enrol babies and young children.
The same thing, for a scientist
A complete read of the ClinicalTrials.gov records for AUGMENT-101 (NCT04065399, revumenib, from 30 days of age, n=447), KOMET-001 (NCT04067336, ziftomenib, adults only, n=263) and cAMeLot-1 (NCT04811560, bleximenib, from 2 years, n=420) on 2026-09-18 found **zero endocrine outcome measures** among the primary, secondary and other outcomes of any of the three [E1][E2][E3]. No calcium, phosphate, PTH, IGF-1, prolactin, thyroid function, fasting glucose, insulin, gastrin, height velocity, bone age or pubertal staging appears as an outcome measure or in any eligibility criterion. The only measured parameters adjacent to the endocrine system are QTc (cardiac), potassium and magnesium correction (as QTc management), and generic 'adequate organ function' at entry. This absence is a finding and it is specific: the endocrine data that exist for revumenib exist because they were in the **laboratory panel**, not because they were an endpoint - which is why they reached the FDA label and never reached the pivotal publication [E4].
What each trial does collect1 deeper
| Trial | Drug | Min age | Endocrine outcome measure | Endocrine eligibility criterion |
|---|---|---|---|---|
| NCT04065399 AUGMENT-101 | revumenib | 30 days | none | none (QTcF >450 ms excluded; 'adequate organ function') |
| NCT04067336 KOMET-001 | ziftomenib | 18 years | none | none (QTcF >480 ms excluded) |
| NCT04811560 cAMeLot-1 | bleximenib | 2 years | none | none (QTcF thresholds; renal function by Schwartz formula in children) |
Outcome measures across all three are: dose-limiting toxicities, treatment-emergent adverse events by CTCAE v5.0, pharmacokinetics (Cmax, Tmax, AUC), CR/CRh and composite remission rates, MRD negativity, duration of response, time to response, transfusion independence, event-free and overall survival, and for one sub-study ECOG change and QTc 123.
The asymmetry is worth naming plainly. AUGMENT-101 enrols from 30 days of age and has adjusted its dosing by body surface area for children under 40 kg, so the programme has taken paediatric development seriously in every respect except the one that concerns what happens to those children after the leukaemia is gone.
The publication gap, separately
The pivotal AUGMENT-101 phase II publication (n=94, median treatment duration 10 weeks, 23 children with median age 4.0 years) prespecified its adverse events of special interest as differentiation syndrome, QTc prolongation and peripheral neuropathy. Its adverse-event table lists no parathyroid, calcium or phosphate entry; hypokalaemia is the only electrolyte abnormality reported 4.
So a clinician reading the peer-reviewed literature would not learn that intact PTH rose in 34% of patients, or that hyperparathyroidism is a labelled endocrine adverse reaction, or that juvenile rats fused their growth plates irreversibly. All three facts are in the regulatory documents. This is a reporting-channel failure, not a measurement failure, and it is the more tractable of the two problems: it requires a publication, not a new trial.
What an absence does and does not license
Does license: the statement that no registered menin-inhibitor trial has a prespecified endocrine endpoint, and therefore that no menin-inhibitor trial can currently produce a designed answer about endocrine safety. Adverse-event capture is passive; it detects what clinicians happen to notice and code, which for an asymptomatic calcium of 2.70 mmol/L in a child on chemotherapy is close to nothing.
Does not license: the claim that nothing was measured. The revumenib label proves otherwise for PTH, phosphate and calcium. And it does not license the claim that nobody is looking, because FDA's postmarketing requirement 4730-1 compels exactly this study with a 2028 report (reg-fda-pmr-endocrine-chronic-menin-inhibition).
The precise, defensible statement is: the endocrine data being generated are incidental rather than designed, are absent from the paediatric-relevant domains entirely, and are not being published.
| audit date | 2026-09-18 |
|---|---|
| source | ClinicalTrials.gov API v2, full outcome and eligibility records |
| publication gap | intact PTH 34%, labelled hyperparathyroidism and the juvenile-rat growth-plate finding appear in FDA documents and in none of the peer-reviewed reports |
trials — the numbers behind the chart
[
{
"nct": "NCT04065399",
"acronym": "AUGMENT-101",
"drug": "revumenib",
"minimum_age": "30 Days",
"enrollment": 447,
"endocrine_outcome_measures": 0,
"endocrine_eligibility_criteria": 0
},
{
"nct": "NCT04067336",
"acronym": "KOMET-001",
"drug": "ziftomenib",
"minimum_age": "18 Years",
"enrollment": 263,
"endocrine_outcome_measures": 0,
"endocrine_eligibility_criteria": 0
},
{
"nct": "NCT04811560",
"acronym": "cAMeLot-1",
"drug": "bleximenib",
"minimum_age": "2 Years",
"enrollment": 420,
"endocrine_outcome_measures": 0,
"endocrine_eligibility_criteria": 0
}
]parameters searched for
[ "calcium", "phosphate", "parathyroid hormone", "IGF-1", "prolactin", "TSH", "free T4", "fasting glucose", "insulin", "C-peptide", "gastrin", "chromogranin A", "height velocity", "bone age", "Tanner stage" ]
parameters found
[]
nearest adjacent measures
[ "QTc interval (cardiac)", "potassium and magnesium correction for QTc management", "adequate organ function at entry" ]
- A registry record is not a protocol. The strongest objection to this entry is that it audits what was registered, not what was measured, and the revumenib label demonstrates that at least one endocrine analyte was measured without appearing in the registry.
- Adding endpoints to a phase 1/2 trial in relapsed leukaemia has real costs - assay burden, protocol amendments, additional blood volume in small children - and the trials' designers reasonably prioritised remission and survival in a population with months to live.
- The absence of a prespecified endpoint is not the absence of oversight: FDA's postmarketing requirement 4730-1 compels precisely this assessment with a 2028 report, so the correct framing is a timing gap, not a blind spot.
- Do the case report forms for any of the three trials collect calcium, PTH or growth data that are simply not registered as outcome measures? For revumenib the label proves PTH was collected; for bleximenib, which enrols two-year-olds, nobody has asked.
- Why did the pivotal publication omit an adverse reaction that FDA considered important enough to put on the label under Endocrine disorders? Answering this would tell the field whether the omission was an editorial threshold or a reporting decision.
- Would a single cross-programme publication of the existing laboratory data resolve most of this beat without any new trial? The analytes exist in three sponsor databases.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
The ClinicalTrials.gov record for AUGMENT-101 (NCT04065399, revumenib, enrolment 447, patients aged 30 days and older) lists primary and secondary outcome measures comprising dose-limiting toxicities, treatment-emergent adverse events by CTCAE v5.0, Cmax, Tmax, AUC, CR+CRh rate, composite CR, overall response rate, time to response, duration of response, event-free survival, overall survival and transfusion independence, and contains no endocrine outcome measure and no endocrine eligibility criterion.
AUGMENT-101: A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation · Syndax Pharmaceuticals · ClinicalTrials.gov 2026What this evidence cannot show
Read in full via the ClinicalTrials.gov API on 2026-09-18, including all primary, secondary and other outcome measures and the complete eligibility text. A registry record is a summary of the protocol, not the protocol: case report forms may collect parameters that are never registered as outcome measures, and the FDA label proves that intact PTH was collected in this programme despite not appearing here. The absence is therefore of a prespecified endpoint, not necessarily of measurement.
Evidence that argues against this (1)
- The FDA label for revumenib reports intact PTH in 34%, phosphate in 51% and corrected calcium in 15% of the pooled safety population, which demonstrates directly that these analytes were measured in the AUGMENT-101 programme even though the registry lists no endocrine outcome measure. An absence from a registry record is weak evidence about what a trial measures. Syndax Pharmaceuticals / US FDA 2025
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
The ClinicalTrials.gov record for KOMET-001 (NCT04067336, ziftomenib, enrolment 263, minimum age 18 years) lists outcome measures comprising MTD/RP2D, adverse events by CTCAE v5.0, minimum biologically effective dose, CR+CRh and CRc rates, MRD negativity, duration of response, transfusion independence, overall response rate, event-free and overall survival, pharmacokinetic parameters for ziftomenib, midazolam and itraconazole, ECOG change and QTc intervals, and contains no endocrine outcome measure and no endocrine eligibility criterion.
KOMET-001: First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia · Kura Oncology, Inc. · ClinicalTrials.gov 2026What this evidence cannot show
Read in full via the ClinicalTrials.gov API on 2026-09-18. This trial enrols adults only, so paediatric endocrine endpoints would not be expected; the relevant absence is of any calcium, phosphate or PTH collection, which is consistent with the KOMZIFTI label's laboratory table containing no such row.
Evidence that argues against this (1)
- A registry outcome list is the protocol's PRESPECIFIED measures, not everything collected. Laboratory chemistry including calcium is captured routinely under adverse-event monitoring in essentially every oncology trial, so absence from the outcome list means the endpoint was not powered or analysed, not that the data do not exist. That distinction matters because it makes the data recoverable. ClinicalTrials.gov 2026
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
The ClinicalTrials.gov record for cAMeLot-1 (NCT04811560, bleximenib, enrolment 420, paediatric cohort from 2 years of age) lists outcome measures comprising adverse events and their severity, dose-limiting toxicity, CR/CRh rate, plasma concentration of bleximenib, overall response rate, duration of response, time to response, MRD negativity, event-free survival, overall survival and transfusion independence, and contains no endocrine outcome measure; eligibility specifies renal function by the CKiD Schwartz formula for children but no endocrine parameter.
cAMeLot-1: A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia · Janssen Research & Development, LLC · ClinicalTrials.gov 2026What this evidence cannot show
Read in full via the ClinicalTrials.gov API on 2026-09-18. This trial explicitly enrols children from 2 years with paediatric-specific renal and performance-status criteria, which shows the protocol was adapted for children in other respects, making the endocrine omission a choice rather than an oversight of paediatric design generally.
Evidence that argues against this (1)
- cAMeLot-1's paediatric cohort from age 2 is the most relevant population in the registry for this question, and its outcome list is the wrong place to look for whether endocrine signals will be detected - the protocol's adverse-event grading and its stopping rules matter more. The entry infers absence of surveillance from absence of an endpoint. ClinicalTrials.gov 2026
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The pivotal AUGMENT-101 phase II publication (94 patients including 23 children, median age 4.0 years in the paediatric group, median treatment duration 10 weeks) prespecified differentiation syndrome, QTc prolongation and peripheral neuropathy as adverse events of special interest and reports no parathyroid, calcium or phosphate abnormality in its adverse-event table, in which hypokalaemia (27.7%) is the only electrolyte entry.
Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). · Issa GC, Aldoss I, Thirman MJ, DiPersio J, Arellano M, Blachly JS, et al., Stein EM · J Clin Oncol 43:75-84 2024What this evidence cannot show
Read in full text via PubMed Central on 2026-09-18. The paper does not state which laboratory analytes were collected, so this is evidence about reporting rather than measurement. The data supplement was not retrieved and could in principle contain laboratory tables not described in the main text.
Evidence that argues against this (1)
- The adverse events of special interest being differentiation syndrome, QTc prolongation and peripheral neuropathy is what makes this publication silent on endocrine risk in BOTH directions, and the entry should not be read as showing an absence of effect. With a ten-week median exposure and 23 children, the study is also too short and too small to detect a slow endocrine phenotype even had it looked. Journal of Clinical Oncology 2025
the endpoint gap in the trials is what the postmarketing requirement is meant to close, minus its own paediatric and off-treatment gaps
cAMeLot-1 enrols children from 2 years with paediatric-specific renal criteria and no endocrine measure at all
the label mandates monitoring bone growth in children and no trial operationalises it
fills the endpoint gap the registry audit documents
no endpoint in any lead trial could detect an ER-axis effect
Extends the registry absence to the labels: PTH survived into the REVUFORJ table, glucose did not survive into either, despite being on every routine chemistry panel