ASH 2025 – Kura seeks further safety edge

Kura already got an edge over its menin inhibitor rival Syndax by avoiding a black box warning of QTc prolongation for Komzifti, and it now reckons it can go even further, it told ApexOnco during ASH.

The Kyowa Kirin-partnered Komzifti got the FDA nod last month for relapsed/refractory AML with NPM1 mutations. Whereas Syndax’s Revuforj has a boxed warning for QTc prolongation, Komzifti's label carries only a regular warning for this; and Kura has already begun discussions with the FDA to get even this warning removed, according to its chief medical officer, Mollie Leoni. 

“We truly don’t believe that we cause a QTc prolongation; we think it was the QTc-prolonging meds that the patients were also on that would’ve caused that effect. We just need sufficient data,” she told ApexOnco.

The company has a couple of options to argue its case. One is using results from the ongoing randomised controlled Komet-017 first-line trial, while the second could involve additional data from the uncontrolled Komet-001 trial, which supported the recent approval.

“The supposition [the FDA] put to us is this is a single-arm trial, so you can’t exclude [QTc prolongation] because you don’t have a randomised arm,” said Kura’s chief executive, Troy Wilson. “Had we continued to negotiate this with the agency it would’ve delayed the PDUFA date.”

Komet-017, which encompasses both chemo-eligible and chemo-ineligible patients, dosed its first patient in September. First readout is expected in 2028, on the MRD-negative complete response endpoint in the chemo-eligible arm, Wilson said.

Komet-007

At ASH on Monday Kura reported data from Komzifti combos in the Komet-007 trial in both first-line and relapsed/refractory AML.

In the front line Komzifti plus Venclexta and azacitidine produced a composite complete remission (CRc) rate of 86% among 37 NPM1m patients, similar to the abstract.

In relapsed/refractory disease the Komzifti Ven/aza combo produced a CRc rate of 48% among patients with NPM1m – versus a 21% CR/CRh rate with Komzifti monotherapy in this setting. “You’re seeing a meaningful improvement relative to either Venclexta or Komzifti as individual therapies,” Wilson noted.

However, Kura doesn’t plan to pursue formal regulatory approval of this combo in relapsed/refractory disease, with the focus now squarely on the front line. Instead it aims to get this combo included in the National Comprehensive Cancer Network (NCCN) guidelines.

The first-line battleground also includes Syndax, whose Revuforj is in the phase 3 investigator-sponsored Evolve-2 trial in chemo-ineligible patients, with the Reveal-ND trials slated to start soon in the chemo-eligible population.

Meanwhile, Johnson & Johnson began a phase 3 trial in April of its contender bleximenib in newly diagnosed chemo-ineligible patients. An investigator-sponsored pivotal trial is slated to start soon in the chemo-eligible setting.

Phase 3 trials of menin inhibitors in first-line AML

Note: *investigator-sponsored trial. Source: OncologyPipeline & clinicaltrials.gov.