This Phase 1/2 clinical trial (NCT01371630), led by the University of Texas MD Anderson Cancer Center, evaluated the efficacy of combining Besponsa (inotuzumab ozogamicin), Pfizer's CD22-targeting antibody-drug conjugate (ADC), with a low-dose 'mini-hyper-CVD' chemotherapy regimen. Traditional high-dose chemotherapy regimens have limitations, including significant toxicity in older patients or those with relapsed/refractory ('R/R') B-cell acute lymphoblastic leukemia ('B-ALL'), leading to high rates of treatment discontinuation. This study represents a strategic, biomarker-driven approach aimed at maximizing therapeutic response and minimizing side effects by combining Besponsa's targeted precision with a reduced chemotherapy intensity.

Besponsa is a next-generation ADC that consists of a monoclonal antibody targeting the CD22 receptor, which is overexpressed on B-cells, conjugated to the potent cytotoxic agent calicheamicin via a linker. The drug functions by selectively binding to CD22-positive cancer cells, internalizing, and directly destroying the cancer cells' DNA, leading to cell death. Combining this with chemotherapy, which inhibits cancer cell proliferation, provides a multi-pronged attack on cancer cells, overcoming drug resistance and improving long-term survival.

The mature analysis of the study, which included a total of 110 patients, demonstrated an objective response rate (ORR) of 83% (91 patients) and a complete remission rate (CR) of 63% (69 patients). The median overall survival (OS) was 17 months. In the cohort that sequentially received blinatumomab, the 3-year survival rate was 52%, compared to 34% in the single-combination group, although this difference was not statistically significant (p-value = 0.16). While statistical significance was not achieved, the results are promising, considering that the survival rate in patients receiving chemotherapy alone was only a few months, suggesting the potential for a new standard of care for older patients.

The global acute lymphoblastic leukemia (ALL) therapeutics market is currently valued at $3.1 billion in 2023 and is projected to grow to $4.9 billion by 2030, with an annual growth rate of 7%. In this market, Pfizer competes with Amgen's Blincyto (blinatumomab), a CD19/CD3 bispecific T-cell engager (BiTE), and Novartis' Kymriah (tisagenlecleucel), a CAR-T cell therapy. Besponsa received FDA approval for adult patients in August 2017 and expanded its indication to include pediatric patients in March 2024, accumulating strong clinical data and strengthening its market position.

Based on the data from this investigator-initiated trial (IIT) conducted in collaboration with MD Anderson Cancer Center, Pfizer is conducting additional trials to incorporate the Besponsa and low-dose chemotherapy combination into the treatment of B-ALL. To address concerns about veno-occlusive disease (VOD), a side effect observed during the initial approval in 2017, the company is focusing on improving safety by fractionating the dosing. The industry believes that this trial, which achieves both reduced toxicity and improved remission rates, will overcome the limitations of existing cancer therapies and establish a new combination therapy protocol.