Johnson & Johnson / Janssen — bleximenib (JNJ-75276617): paediatric from age 2, but not infants, and the dedicated child study was withdrawn
also called J&J · Janssen · Janssen Research & Development · JNJ-75276617 · bleximenib · cAMeLot-1
Johnson & Johnson's menin inhibitor bleximenib is the only one whose company-run first-in-human trial openly enrols children, but the floor is two years old, which excludes infants. A separate paediatric combination study the company registered was withdrawn before enrolling anyone.
The same thing, for a scientist
Janssen Research & Development (Johnson & Johnson) developed bleximenib (JNJ-75276617), a potent, selective, orally bioavailable inhibitor of the menin-KMT2A protein-protein interaction with a co-crystal-confirmed binding mode distinct from revumenib, retaining activity against MEN1 M327I and T349M resistance mutations [E1]. The first-in-human study cAMeLot-1 (NCT04811560) is phase 1/2 in R/R acute leukaemia with KMT2A, NPM1, NUP98 or NUP214 alterations and registers a minimum age of 2 years, with an explicit paediatric cohort of 2 to under 18 in phase 1 and adults only in phase 2 [E2]. Bleximenib is unapproved. The combination and phase 3 programme (NCT05453903, NCT06852222) is adult AML [E3]. A registered phase 1/1b of bleximenib plus conventional chemotherapy specifically for paediatric and young adult R/R acute leukaemias, NCT05521087, was withdrawn with zero enrolment [E4].
The age picture: better than Kura, worse than Syndax, and it moved backwards1 deeper
| Study | NCT | Phase | Status | Sponsor | Minimum age |
|---|---|---|---|---|---|
| cAMeLot-1 (first-in-human, R/R acute leukaemia) | NCT04811560 | 1/2 | Recruiting | Janssen R&D | 2 years (paediatric cohort 2 to <18 in phase 1; phase 2 is >18) 2 |
| Bleximenib + AML-directed therapies (ven/aza; 7+3) | NCT05453903 | 1b | Active, not recruiting | Janssen R&D | adult AML programme 3 |
| Bleximenib + venetoclax + azacitidine, newly diagnosed AML ineligible for intensive chemotherapy | NCT06852222 | 3 | Recruiting | Janssen R&D | 18 years 3 |
| Bleximenib + induction/consolidation, newly diagnosed KMT2A-r or NPM1-m AML | NCT07223814 | 3 | Recruiting | HOVON (Dutch adult haemato-oncology foundation) | adults 3 |
| Bleximenib + conventional chemotherapy, paediatric and young adult R/R acute leukaemias | NCT05521087 | 1/1b | Withdrawn, 0 enrolled | Janssen R&D | — 4 |
Two things follow for an infant-ALL programme.
First, 2 years is not infancy. Infant ALL is defined by diagnosis under 12 months, and roughly 75-80% of it is KMT2A-rearranged. A trial floor of 24 months excludes the entire population by construction. Bleximenib's paediatric cohort covers school-age and adolescent KMT2A-rearranged disease, which is a different and less KMT2A-dominated biology.
Second, and more informative, J&J registered a dedicated paediatric combination study and then withdrew it without enrolling a single patient 4. NCT05521087 would have combined bleximenib with fludarabine/cytarabine and with a vincristine/dexamethasone/pegaspargase backbone in children and young adults with R/R KMT2A-, NPM1- or nucleoporin-altered acute leukaemia — exactly the design a paediatric partner would want. Its withdrawal is the single clearest signal in this node about where J&J's paediatric commitment actually sits. The registry does not give a reason, and a withdrawal can reflect anything from portfolio reprioritisation to a competitor reading the same market; inferring intent from a registry status field would be overreach. But the operational fact is unambiguous: that study will not produce paediatric bleximenib data.
Paediatric infrastructure exists even if the paediatric study does not
cAMeLot-1's site list is unusually revealing. Among its 102 registered sites are UCSF Benioff Children's Hospital, Hôpital Trousseau (APHP) in Paris and Hospital Infantil Universitario Niño Jesús in Madrid 2 — dedicated children's hospitals that would not be activated for an adults-only protocol. The protocol also carries paediatric-specific machinery: Lansky performance status for patients under 16, and a CKiD Schwartz formula GFR threshold of 40 mL/min for paediatric participants rather than the adult MDRD threshold.
That is the tell. The operational capacity to dose children with bleximenib is built and activated. The barrier to infants is a protocol decision, not missing infrastructure — which means it is in principle amendable, and an academic group with a strong infant rationale is arguing about a number rather than about a capability.
What J&J owns that an academic lab cannot generate
A structurally differentiated compound with published resistance coverage. The Blood preclinical paper reports a co-crystal structure of menin with bleximenib showing a binding mode distinct from other menin-KMT2A inhibitors including revumenib, and potent antiproliferative activity in cell lines engineered with MEN1 M327I and T349M — the mutations that emerged in patients refractory to revumenib 1. Bleximenib also showed synergy with gilteritinib, and with venetoclax plus azacitidine, in KMT2A-rearranged AML cells. For a laboratory interested in whether menin-inhibitor resistance is a class property or a compound property, bleximenib is the necessary second compound and cannot be substituted.
Scale that is not available from a mid-cap. The phase 3 NCT06852222 registers 262 sites and 600 participants 3. J&J can run global registration trials in a rare genotype; that capacity is the asset, and nothing an academic group does substitutes for it.
Patient material across a wide age span. cAMeLot-1's combined paediatric and adult enrolment, with a target of 420, is the broadest single-compound age range in this class after Syndax's.
What J&J lacks. Infant biology. The company has no infant protocol, has withdrawn its paediatric combination study, and its remaining paediatric exposure is a phase 1 cohort inside a study whose phase 2 is adults-only. If bleximenib is ever to be justified in infants, the preclinical and mechanistic case will have to be made from outside the company.
Is a collaboration realistically possible?
Honest answer: harder than with Syndax, easier than it looks from the withdrawn study.
Against: J&J is the largest organisation in this landscape, its decision-making is slow and portfolio-driven, and it has just demonstrated by withdrawing NCT05521087 that paediatric bleximenib is not a protected priority. A small academic laboratory has no natural channel into Janssen R&D oncology.
For: bleximenib already circulates outside J&J's own protocols. It appears as a sub-study agent inside the Beat AML master protocol (NCT03013998, sub-study S25/HO181) and the Dutch HOVON group sponsors a phase 3 with it (NCT07223814) 3. J&J therefore does supply compound to consortium-run studies it does not control.
The realistic ask is narrow and preclinical: compound supply for infant-ALL patient-derived xenograft and primary-sample work, framed around the one question the Blood paper opens and does not close — whether bleximenib's distinct binding mode preserves activity in KMT2A-rearranged infant blasts that have escaped revumenib. That is a small, cheap request that generates data J&J would want and cannot easily buy, and it does not require J&J to open a trial. It is also the honest prerequisite for ever arguing that the age floor should come down from 2 years.
| group | Janssen Research & Development, LLC (Johnson & Johnson Innovative Medicine), Discovery Oncology |
|---|---|
| institution | Johnson & Johnson / Janssen R&D — Beerse (Belgium), Spring House (Pennsylvania, USA), Shanghai (China), Cambridge (Massachusetts, USA) |
| focus | Menin-KMT2A protein-protein interaction inhibition in KMT2A-rearranged, NPM1-mutant and nucleoporin-altered acute leukaemia; combination with venetoclax/azacitidine, intensive chemotherapy and FLT3 inhibitors |
| stage | Clinical, phase 3; bleximenib is not approved by any regulator |
| lead asset | bleximenib (JNJ-75276617) — oral, selective, reversible menin-KMT2A interaction inhibitor with a co-crystal-confirmed binding mode distinct from revumenib |
| pediatric inclusive | true |
| min age eligible | 2 years, in the phase 1 paediatric cohort of cAMeLot-1 (NCT04811560) only; phase 2 of the same study and the whole phase 3 programme require 18 years. Infants under 2 are excluded everywhere, and the dedicated paediatric combination study NCT05521087 was withdrawn with zero enrolment. |
| approval status | Not approved. Investigational; phase 3 ongoing in newly diagnosed AML. |
| combination strategy | Bleximenib is being developed almost exclusively as a combination agent: with venetoclax + azacitidine in non-intensive-eligible newly diagnosed AML (phase 3 NCT06852222), with 7+3 intensive induction (NCT05453903, and the HOVON phase 3 NCT07223814), and preclinically with gilteritinib in FLT3-co-altered KMT2A-rearranged AML. |
| partnering angle | Not a trial partnership. The tractable ask is compound supply for preclinical infant-ALL work — patient-derived xenografts and primary blasts — testing whether bleximenib's distinct menin binding mode retains activity in KMT2A-rearranged infant disease that has escaped revumenib. That question is opened but not closed by J&J's own Blood paper, costs the company nothing operationally, and is the necessary evidence base for ever arguing the cAMeLot-1 age floor down from 2 years. |
trials
[ "NCT04811560", "NCT05453903", "NCT06852222", "NCT07295951", "NCT05521087", "NCT07223814", "NCT03013998" ]
key papers
[
{
"title": "Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias",
"year": 2024,
"venue": "Blood",
"pmid": "38905635",
"doi": "10.1182/blood.2023022480"
},
{
"title": "Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review",
"year": 2025,
"venue": "Diseases",
"pmid": "40710017",
"doi": "10.3390/diseases13070227"
}
]- A floor of 2 years excludes infant ALL entirely by definition, so any collaboration framed around cAMeLot-1 will not touch the population of interest.
- The withdrawal of the paediatric combination study shows that paediatric commitment at a company this size is reversible without explanation, which makes any plan contingent on a J&J paediatric protocol fragile.
- Bleximenib's whole registration strategy is combination therapy with venetoclax/azacitidine or 7+3 backbones designed for adults; the combination partners themselves may be the obstacle to paediatric extension, not the menin inhibitor.
- Preclinical resistance coverage demonstrated in engineered MEN1-mutant lines is a weak predictor of clinical cross-resistance, so the central scientific selling point of this compound is currently unvalidated in patients.
- Why was NCT05521087, the dedicated paediatric bleximenib combination study, withdrawn before enrolling anyone? The registry gives no reason and the answer determines whether paediatric bleximenib is dormant or dead.
- How many children aged 2 to 17 have actually been dosed in the cAMeLot-1 paediatric cohort, and with what toxicity? The cohort is registered but no paediatric-specific results have been reported.
- Does bleximenib's distinct binding mode translate into clinical activity after revumenib failure in patients, as opposed to in MEN1-mutant engineered cell lines?
- Is there a pharmacological reason the age floor is 2 rather than lower — formulation, a juvenile toxicology finding, PK modelling — or is it a conventional default? Nothing public distinguishes these.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Bleximenib (JNJ-75276617) is a potent, selective, orally bioavailable menin-KMT2A protein-protein interaction inhibitor whose co-crystal structure with menin shows a binding mode distinct from other menin-KMT2A inhibitors including revumenib, and which retains potent antiproliferative activity in cell lines engineered with the MEN1 M327I and T349M mutations that arose in patients refractory to revumenib.
Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias · Kwon MC, Thuring JW, Querolle O, Dai X, Verhulst T, Pande V, et al. · Blood 2024What this evidence cannot show
Preclinical only: cell lines, patient samples in vitro and mouse xenografts. Resistance-mutation activity was shown in engineered lines, not in patients who had failed revumenib. Authorship is predominantly Janssen R&D employees, so the framing and the choice of comparators are those of an interested party, although the co-crystal structure and the resistance-line data are hard experimental results. According to PubMed; DOI https://doi.org/10.1182/blood.2023022480
Evidence that argues against this (1)
- Weakens the inference, not the fact. The sponsor's own paper establishes that bleximenib has a distinct co-crystal binding mode and retains activity against engineered MEN1 M327I and T349M. What it cannot establish, because it tests only its own compound, is that retention of activity against revumenib resistance mutations is a property of bleximenib's particular binding mode. The Michigan group's 2026 Blood paper on ziftomenib -- a third compound, chemically and structurally distinct from both -- reports that ziftomenib also retains antileukaemic activity against T349M and shows low-nanomolar potency (GI50 <= 25 nM) against G331R, with co-crystal structures of ziftomenib bound to menin WT, T349M and G331R showing a similar binding mode in each, while M327I and G331D remain resistant. Two readings follow. (1) Partial escape of revumenib-resistant MEN1 variants is a general feature of second-generation menin inhibitors rather than a bleximenib differentiator, so it is weak grounds for preferring bleximenib. (2) More importantly for this project's central hypothesis, two independently derived compounds converge on the same non-covered mutants: M327I defeats revumenib and ziftomenib both, and G331D defeats ziftomenib. The interface has a small set of residues that break the whole drug class, which is what one would expect if the druggable handle is a single pocket rather than a redundant surface. Caveats: all mutant data in both papers are from engineered cell lines, not patient material; no head-to-head comparison of the three compounds against the same mutant panel in the same assay has been published; sponsor employees are authors on both papers (Janssen on the bleximenib paper, Kura Oncology and Wellspring Biosciences on the ziftomenib paper). Read: abstract only. Miao H et al. 2026
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
cAMeLot-1 (NCT04811560) is a Janssen-sponsored phase 1/2 first-in-human study of bleximenib in R/R acute leukaemia with KMT2A, NPM1, NUP98 or NUP214 alterations, currently recruiting across 102 sites with a target of 420 participants, and registers a minimum age of 2 years with an explicit paediatric cohort of age 2 to under 18 in phase 1; phase 2 is restricted to participants over 18.
A Phase 1/2, First-in-Human Study of the Menin-KMT2A (MLL1) Inhibitor Bleximenib in Participants With Acute Leukemia (cAMeLot-1) · Janssen Research & Development, LLC · ClinicalTrials.gov 2021What this evidence cannot show
Sponsor-submitted record describing protocol eligibility, not realised enrolment; the number of children aged 2 to 17 actually dosed is not reported anywhere. The structured minimum-age field reads 2 years and the eligibility text confirms 'Age 2 years to less than 18 years of age (pediatric cohort only)'. Down-syndrome-associated leukaemia and juvenile myelomonocytic leukaemia are excluded. Record retrieved and read 2026-09-18.
Evidence that argues against this (1)
- A registry field is a snapshot with a date on it. Status, site count, target enrolment and eligibility are edited by sponsors between checks, and this graph has already recorded one trial whose status string changed under it. Anything planned on these numbers has to re-query them rather than read them here. A 102-site footprint and a 420-participant target are planning figures; actual enrolment in the paediatric cohort of a first-in-human study is the number that matters and it is not in the registry field quoted. U.S. National Library of Medicine 2026
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registry
The bleximenib combination and registration programme is adult: NCT05453903 (phase 1b, bleximenib with venetoclax/azacitidine or intensive chemotherapy, active not recruiting, n=196) and NCT06852222 (phase 3, bleximenib + venetoclax + azacitidine in newly diagnosed AML ineligible for intensive chemotherapy, recruiting, 262 sites, n=600, minimum age 18); bleximenib also appears in consortium studies J&J does not sponsor, including the Beat AML master protocol sub-study S25/HO181 (NCT03013998) and the HOVON-sponsored phase 3 NCT07223814.
ClinicalTrials.gov registry records for NCT05453903, NCT06852222, NCT03013998 and NCT07223814, retrieved via the ClinicalTrials.gov API v2 intervention search on bleximenib / JNJ-75276617 · Janssen Research & Development, LLC; Beat AML, LLC; Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON) · ClinicalTrials.gov 2026What this evidence cannot show
The minimum age was checked directly for NCT06852222 (18 years) but not individually for NCT05453903, which is described here only by its registered adult-AML population, phase, status and enrolment. Appearance of a compound in a consortium master protocol does not establish the terms of supply. Retrieved 2026-09-18.
Evidence that argues against this (1)
- A registry field is a snapshot with a date on it. Status, site count, target enrolment and eligibility are edited by sponsors between checks, and this graph has already recorded one trial whose status string changed under it. Anything planned on these numbers has to re-query them rather than read them here. The entry's substantive point stands and should be stated as the conclusion rather than the list: every bleximenib study capable of supporting a label enrols adults only, so paediatric evidence will follow adult approval as it did for the two approved menin inhibitors. U.S. National Library of Medicine 2026
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
Janssen registered a phase 1/1b study of JNJ-75276617 in combination with conventional chemotherapy for paediatric and young adult participants with relapsed/refractory acute leukaemias harbouring KMT2A, NPM1 or nucleoporin gene alterations (NCT05521087), and that study is recorded as withdrawn with an enrolment of zero.
A Phase I/Ib Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias Harboring KMT2A, NPM1, or Nucleoporin Gene Alterations · Janssen Research & Development, LLC · ClinicalTrials.gov 2026What this evidence cannot show
The registry records the status 'withdrawn' and enrolment 0 but gives no reason, and a withdrawn registration can reflect portfolio reprioritisation, a protocol redesign that reappears under a new number, competitive landscape, or a regulatory issue. Do not infer motive from this field. Retrieved 2026-09-18.
Evidence that argues against this (1)
- Corrects this entry. The entry's first open question asserts that 'the registry gives no reason' for the withdrawal of NCT05521087. It does: the ClinicalTrials.gov record carries WhyStopped = 'Business Decision' (retrieved via the ClinicalTrials.gov API v2, 2026-09-18). Two further registry facts materially change what this trial meant. First, its registered minimum age was 30 days, not 2 years -- so Janssen did design, register and then withdraw a genuinely infant-inclusive bleximenib study, and the 2-year floor described elsewhere in this entry is the floor of what survived, not of what was ever planned. Second, a business-decision withdrawal at zero enrolment carries no information about paediatric safety or about bleximenib in infant disease, which means the entry's framing of paediatric bleximenib as possibly 'dead' on scientific grounds is not supported. The practical read for a lab: the obstacle to infant bleximenib is commercial prioritisation, which an external academic sponsor willing to run the study could in principle route around, and not a juvenile toxicology finding, which it could not. Caveat: 'Business Decision' is sponsor-submitted free text with no further detail, and the registry does not say whose decision or why. Read: registry record only. Janssen Research & Development et al. 2026
- E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.review
Independent review literature places bleximenib among six menin inhibitors in clinical evaluation (with revumenib, ziftomenib, enzomenib, DS-1594 and BMF-219) and treats it as one of the four most extensively studied.
Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review · Canichella M, Papayannidis C, Mazzone C, de Fabritiis P · Diseases 2025What this evidence cannot show
A narrative review in a low-impact journal, not primary data; it summarises sponsor-reported efficacy and inherits those biases. Useful for establishing the composition of the competitive field, not for comparing compounds — no head-to-head trial of any two menin inhibitors exists. According to PubMed; DOI https://doi.org/10.3390/diseases13070227
Evidence that argues against this (1)
- Placement among "the four most extensively studied" is a review's judgement at its submission date and tracks publication volume rather than clinical promise. The same review literature ranked the field differently two years earlier. Journal of Clinical Oncology 2025
- ← related toThe counter-argument: the menin field is an adult field, and the infant studies were withdrawn
withdrawn paediatric bleximenib study NCT05521087
Counter-evidence (NCT05521087 WhyStopped = 'Business Decision', MinimumAge = 30 days): J&J registered and then withdrew a genuinely infant-inclusive bleximenib study for commercial reasons, not for a paediatric safety finding
Counter-evidence (Miao 2026, PMID 41849234): ziftomenib also retains activity against T349M and G331R with matching co-crystals, so escape of revumenib-resistance mutants is a class property rather than a bleximenib differentiator -- and M327I/G331D defeat more than one compound, implying a small shared breaking set at the interface
Cross-compound resistance comparison: bleximenib covers M327I, ziftomenib does not; ziftomenib covers G331R, which the bleximenib paper does not test. No head-to-head panel has been published.
sponsor and developer of bleximenib (JNJ-75276617)