Favorable Safety Profile Observed in Phase 1 Study of Acute Myeloid Leukemia Drug

Data suggests favorable tolerability of novel treatment in patients with relapsed or refractory AML.

New data from a phase 1 study of the investigational single-agent IMGN779 shows promise in adults with relapsed or refractory acute myeloid leukemia (AML) with tumors that express CD33.

The findings are the first in-human data to demonstrate the safety and tolerability of IMGN779 across 7 dose levels, as well as evidence of dose-dependent biological and anti-leukemia activity, according to a press release.

“IMGN779 combines a high-affinity, humanized anti-CD33 antibody with one of Immunogen’s novel indolino-benzodiazepine payloads, called IGNs, which alkylate DNA without crosslinking, resulting in potent anti-leukemia activity with relative sparing of normal hematopoietic progenitor cells,” the press release stated.

The goal of the phase 1 trial is to establish the maximum-tolerated dose and determine the recommended phase 2 dose for IMGN779 monotherapy. It is also intended to evaluate safety and tolerability, as well as to characterize pharmacokinetic, pharmacodynamic, and preliminary anti-leukemia activity in relapsed or refractory AML.

“We have designed our DNA-alkylating IGNs to be ultra-potent while providing the tolerability necessary for ongoing treatment,” Richard Gregory, PhD, executive vice president and chief scientific officer of ImmunoGen, said in a release. “We believe that by combining IGNs with our ADC technology, we may be able to treat a number of additional cancers that don’t respond to existing ADC therapies. These data suggest favorable tolerability and encouraging activity in patients with AML, and we look forward to determining the recommended dose for IMGN779 and moving quickly to later-stage development.”

There were several key findings regarding safety, pharmacokinetic, and pharmacodynamic of IMGN779, as well as initial anti-leukemia activity through dose level 7. This included: no dose limiting toxicities were observed through dose level 7, with reported adverse events (AEs) consistent with the underlying disease; no increase in frequency, nature or severity of treatment-emergent AEs with escalating doses were observed, as well as no evidence of cumulative toxicity with repeated dosing.

The findings also showed that favorable pharmacokinetic and pharmacodynamic revealed prolonged exposure and CD33 saturation at dose levels 6 and seven; and initial anti-leukemia activity was observed at dose levels 6 and 7 in patients who failed intensive frontline therapy.

The findings were presented at the 22nd Congress of the European Hematology Association in Madrid, Spain.