Among patients experiencing chronic graft-versus-host disease (cGVHD), the transition of treatment with Niktimvo (axatilimab) to a dose of 0.6 milligrams per kilogram (mg/kg) every four weeks appeared feasible among those treated with a dose of 0.3 mg/kg every two weeks, according to data from the pivotal phase 2 AGAVE-201 trial.
“Overall, these findings support the safety and feasibility of [Niktimvo] at a dose of 0.6 mg/kg monthly,” Dr. Nosha Farhadfar of Methodist Physicians Texas Transplant Specialists - Adult Blood Marrow Transplant, San Antonio in Texas, said during a presentation of the data at the 2025 ASH Annual Meeting. “Future analyses are planned to further evaluate the efficacy and safety at this dosing. Also, I think we need real-world evidence, which is essential to complement this finding and provide a broader support for the therapeutic approach.”
AGAVE-201 Trial Design
In the AGAVE-201 trial, patients who met pre-specified criteria could change their dosing schedule from 0.3 mg/kg every two weeks to 0.6 mg/kg every four weeks, without dose capping. Investigators evaluated the safety and feasibility of transitioning from the approved dose using long-term data from the trial.
Among the 19 patients who transitioned to the 0.6-mg/kg dose, the median age was 50 years, with the majority being male (63.2%). Median time from diagnosis to randomization was 4.39 months and the median number of organs involved was three. The majority of patients reported with severe disease (73.7%), and had previously received an FDA-approved agent (89.5%).
“The subgroup that transitioned to monthly dosing was generally comparable to the overall [population who received the 0.3 mg/kg dose every two weeks,]” Farhadfar said.
Treatment with a dose of 0.6 mg/kg every 4 weeks led to an overall response rate of 94.7%, including partial and complete response rates of 89.5% and 5.3%, respectively.
“One patient with stable disease was transitioned to multi-dosing at the investigator’s discretion,” Farhadfar added.
Toxicities After Switching Doses
After switching doses, patients were on treatment for a median of 20.9 months. At data cutoff, 16 patients (84.2%) maintained the 0.6 mg/kg dose. Of the three who did not, two patients switched back to the FDA-approved dose at 4.6 and 18.6 months following the switch, respectively, while one patient switched back due to an side effect at 3.4 months. In the overall population, the treatment duration was 7.4 months.
Farhadfar noted that the incidence of grade 3 (severe)or higher side effects was higher with the monthly dose compared with the FDA-approved dose (52.6% versus 36.8%, respectively), which was to be expected given the longer treatment duration seen.
“However, when you look at the incidence of treatment-related adverse event, this is similar before and after the monthly dosing, suggesting that the increase in adverse event may be more reflective of longer treatment exposure rather than the direct effect of a new dosing schedule.”
After the switch, there was also a higher incidence of serious side effects (42.1% versus 5.3%, respectively); however, less patients had dose interruptions (21.1% versus 36.8%). Investigators saw a slight increase in the amount of dose reductions (three versus none, respectively) and discontinuations (three versus none).
The most common side effects included fatigue (26.3%), upper respiratory tract infection (26.3%), headache (21.1%), abdominal pain (15.8%), cough (15.8%), creatine phosphokinase increase (15.8%), diarrhea (15.8%), falls (15.8%), oropharyngeal pain (15.8%), pruritis (15.8%) and pyrexia (15.8%).
In August 2024, the FDA approved Niktimvo 0.3 kg/mg every two weeks for the treatment of cGVHD in patients who previously received two or more lines of therapy, based on results from the AGAVE-201 trial. Farhadfar emphasized that the 0.6-mg/kg dose is an investigational schedule change.
“So we need to interpret the results [cautiously], as the available efficacy data for the monthly dosing are limited and the sample size is very small,” she added. “My personal preference is to keep the patient at the every-two-weeks dosing, and consider transitioning to monthly dosing only in a situation where the patients are unable, unwilling or there are some challenges that make this every-two-weeks dosing impractical.”
Reference
“Safety and feasibility of 0.6 mg/kg every 4 weeks dosing of axatilimab in patients treated in the AGAVE-201 study,” by Dr. Nosha Farhadfar et al., Blood.
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