InO is a humanized CD22-targeted antibody conjugated to N-acetyl-γ-calicheamicin, a potent cytotoxic antibiotic. InO was administered to adult patients with R/R CD22+ B-cell ALL in a phase 1/2 (B1931010) study, and a phase 3 (INO-VATE) study that compared single-agent InO with ICC. The goal of this analysis was to quantify differences in response for the endpoints complete response (CR)/CR with incomplete hematologic recovery (CRi) and minimal residual disease-negativity (MRD (-)) for patients treated with InO relative to ICC.
The efficacy endpoints analyzed were CR/CRi per investigator’s assessment and MRD (-). The modeling analyses were performed using generalized binomial logistic regression, which allows constructing a linear continuous predictor for probabilities of response ranging from 0%–100%. 2 treatment arms were considered: single agent InO or ICC (fludarabine, cytarabine, granulocyte colony-stimulating factor; cytarabine with mitoxantrone; or high-dose cytarabine). Additional potential predictors of response (eg, baseline demographic/patient characteristics, laboratory values) were also tested.
For the CR/CRi efficacy endpoint, only 3 variables were statistically significant predictors of achieving CR/CRi: treatment arm, baseline ECOG (BECOG) performance status, and baseline absolute blasts in peripheral blood (BLSTABL). For the MRD (-) endpoint, 5 variables were statistically significant predictors of achieving MRD(-): treatment arm, BECOG performance status, baseline cytogenetic characteristics, prior hematopoietic stem cell transplant before study therapy, and BLSTABL.Table:
|Endpoint, n (%)||Category||Study B1931010 InO (n = 72)||INO-VATE InO Arm (n = 162)||INO-VATE ICC Arm (n = 143)||Total (N = 377)|
|MRD-negativity*||No||31 (43)||59 (36)||115 (80)||205 (54)|
|Yes||41 (57)||97 (60)||23 (16)||161 (43)|
|Missing||0 (0)||6 (4)||5 (3)||11 (3)|
|CR/CRi||No||23 (32)||42 (26)||95 (66)||160 (42)|
|Yes||49 (68)||120 (74)||48 (34)||217 (58)|
When CR/CRi was not achieved and MRD was missing, MRD was considered not achieved.
The odds of achieving CR/CRi and MRD(-) with InO were approximately 7 and 13 times higher, respectively, than ICC.
Clinical trial identification
Legal entity responsible for the study
A. Ruiz-Garcia, E. Vandendries: Employee of and owns stocks in Pfizer Inc. D.J. DeAngelo: Served on advisory boards for Pfizer Inc. H.M. Kantarjian: Received research grants from Pfizer, Amgen, Astex, Novartis, and Bristol-Myers Squib. J. Boni: Was an employee of Pfizer Inc at the time the study was conducted.