J&J catches its menin rivals
The company has caught up with Syndax and overtaken Kura in the first-line menin inhibitor race.
The company has caught up with Syndax and overtaken Kura in the first-line menin inhibitor race.
Syndax was the first player to get a menin inhibitor approved, in relapsed/refractory AML, but in the front line Johnson & Johnson could overtake its smaller rivals: a new phase 3 trial has recently been listed on clinicaltrials.gov for J&J's contender, bleximenib.
The Camelot-2 study, which J&J said was in the works at last year’s ASH meeting, will test bleximenib plus Venclexta and azacitidine in first-line AML patients ineligible for intensive chemo. The trial is slated to begin in May.
In this unfit patient setting, Syndax's Revuforj recently began a phase 3 trial sponsored by the Stichting Hemato-Oncologie voor Volwassenen Nederland (Hovon). Kura has also revealed pivotal plans for its project ziftomenib, but isn’t expecting to start its trials until the second half.
Phase 3 menin inhibitor trials in first-line AML
| Project | Company | Trial | Setting | Regimen | Primary endpoint | Timing |
|---|---|---|---|---|---|---|
| Bleximenib | Johnson & Johnson | Camelot-2 | Chemo-ineligible (NPM1m/KMT2Ar) | + Ven + aza | Complete remission; OS | To start May 2025 |
| Revuforj | Syndax | HO177* | Chemo-ineligible (NPM1m/KMT2Ar) | + Ven + aza | OS in NPM1m | Started Mar 2025 |
| Unnamed | Chemo-eligible (NPM1m/KMT2Ar) | + 7+3 chemo? | Unknown | To start H2 2025 (pending ph1 dose-escalation data) | ||
| Ziftomenib | Kura/Kyowa Kirin | Komet-017-NIC | Chemo-ineligible (NMP1m only) | + Ven + aza | CR (accelerated approval); OS (full approval) | To start H2 2025 |
| Komet-017-IC | Chemo-eligible (NMP1m/KMT2Ar) | + 7+3 chemo | MRD-ve CR (accelerated approval); EFS (full approval) | To start H2 2025 |
Note: *investigator-sponsored trial. Source: OncologyPipeline & clinicaltrials.gov.
There are some differences between the companies’ approaches here. J&J and Syndax will enrol patients with both NPM1 mutations and KMT2A rearrangements, while Kura said it would focus on NPM1 mutants, saying most patients with KMT2Ar disease currently receive intensive chemo followed by stem cell transplant.
Curiously, although the Revuforj trial enrols KMTAr patients, it lists overall survival in NPM1m patients as its primary endpoint.
Fit patients
In the chemo-eligible setting things are less clear, with only Kura disclosing concrete plans so far. That group will measure minimal residual disease-negative complete response as its primary endpoint, in an effort to differentiate itself from 7+3 chemo alone.
J&J hasn’t yet disclosed any pivotal plans here, although in a pre-ASH interview its oncology vice-president of global medical affairs noted that the company was “set up” to start a phase 3 trial with 7+3 chemo, in light of promising early-stage data presented at the meeting with this combo.
Syndax, meanwhile, has promised “multiple” trials of Revuforj plus undisclosed “standard of care regimens” in first-line fit acute leukaemia patients, but appears to be waiting for phase 1 results before it can nail down its go-forward dose; according to the group’s fourth-quarter earnings presentation data are expected in the second half.
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