Preliminary Results of INA03 in R/R Acute Leukemias

Relapsed or refractory (R/R) acute leukemias (AL) are difficult to treat. INA03 is an antibody-drug conjugate (ADC) that delivers microtubule-disrupting agent monomethyl auristatin E (MMAE) to leukemic cells by targeting CD71. Researchers aimed to report the safety and efficacy of INA03 in patients (pts) with R/R AL.

Pts with R/R AL after one treatment line, age >18 years, FEVG >50%, creatinine clearance >30ml/min, normal liver function, and ECOG <2 were eligible for the study. INA03 was administered as an IV infusion on day 1, followed by maintenance injections on specific days. The study has two parts; Part 1 (LD titration, completed) and Part 2 (Dose Escalation) with 3-patient cohorts, aiming to determine MTD, safety, tolerability, and anti-leukemic activity.

Around 22 pts across 8 cohorts were included in this study with a median age of 73 (range: 39 – 83), 20 (91%) pts had AML, and two (9%) had ALL. About 3 (13.6%) pts had a prior allo-SCT, and 12 (54.5%) had prior VEN exposure. Pts received escalating doses of INA03 of 0.02 mg/kg to 2 mg/kg. MMAE pharmacokinetics (PK) appears dose-proportional with a small accumulation after repeated IV, while INA03 PK exhibits target-mediated drug disposition without accumulation. No DLT was observed among the 18 DLT-evaluable pts up to the highest 2 mg/kg dose. No grade 2-4 TEAEs were observed. One related grade 1 TEAE (hyperkalemia/phosphatemia) was reported. Transient reticulocyte count and erythroblast percentage decreases were observed at 0.5 mg/kg and above. Blast reductions were seen in 3/18 evaluable pts at a dose > 1 mg/kg, including two partial responses.

The study found INA03 was well-tolerated up to 2 mg/kg in R/R AL, and the trial is ongoing.

Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.7045#:~:text=Conclusions%3A%20INA03%20is%20well%20tolerated,trial%20continues%20to%20accrue%20patients.

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03957915 

Sylvain Garciaz, Pierre Bories, Leonor Lopez Almeida, Jean-Marie Boher, Coralie Belanger, Christian Recher, Olivier Hermine, Norbert Vey, and Pierre Launay. DOI: 10.1200/JCO.2023.41.16_suppl.7045 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 7045-7045.