Promising Phase 1/2 Trial Results for Evorpacept Combo in Relapsed B-NHL

A recent clinical trial has shown promising results for the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). The study, which was conducted by ALX Oncology, involved the use of evorpacept in conjunction with standard rituximab and lenalidomide, collectively referred to as "R2." Among the 20 participants diagnosed with either indolent or aggressive forms of R/R B-NHL, the combination therapy was well received, exhibiting a safety profile akin to that of the historical R2 regimen.

The innovative approach to treatment yielded impressive outcomes, with an overall response rate (ORR) of 94% and a complete response rate (CRR) of 83% among those with indolent R/R B-NHL. This is particularly noteworthy when compared to the historical CRR benchmark of 34% for R2 alone. The Phase 1/2 investigator-sponsored trial (IST) was presented at the 2024 American Association for Cancer Research (AACR) Annual Meeting, underscoring the significance of these findings within the medical community.

The trial included patients who had previously received rituximab, with the majority having undergone chemoimmunotherapy as well. The dosage of evorpacept ranged from 30 mg/kg every two weeks to 60 mg/kg every four weeks. The treatment was found to be well tolerated, with no dose-limiting toxicities reported. The most common adverse events were fatigue, ALT and AST increase, and anemia, all of which were mostly of a low grade. Importantly, there were no treatment-related fatalities.

Dr. Paolo Strati, the lead investigator of the trial and Assistant Professor of Lymphoma-Myeloma at The University of Texas MD Anderson Cancer Center, highlighted the importance of exploring new combinations with evorpacept. He noted that while standard frontline treatments have shown benefits, many patients experience disease progression post-initial treatment. The favorable safety profile and response rate of evorpacept combined with R2 are encouraging and warrant further exploration in ongoing Phase 2 trials involving previously untreated indolent B-NHL patients.

Sophia Randolph, M.D., Ph.D., Chief Medical Officer at ALX Oncology, emphasized the unique drug design of evorpacept, which has demonstrated anti-cancer activity while minimizing hematologic toxicities associated with other CD47 blocking agents. The positive results from this trial add to the promising data from the ASPEN-01 Phase 1 clinical trial, where evorpacept was combined with rituximab in R/R NHL.

Non-Hodgkin lymphoma (NHL) is a prevalent form of cancer, with approximately half a million new diagnoses worldwide each year. In the United States, it ranks as the seventh most common cancer type. NHL is categorized into indolent and aggressive forms, with the latter being more rapidly progressive. Despite advancements in treatment, NHL, particularly follicular lymphoma, remains a significant cause of mortality.

ALX Oncology, a clinical-stage immuno-oncology company, is dedicated to developing therapies that target the CD47 immune checkpoint pathway, aiming to bridge the innate and adaptive immune systems. Their lead product candidate, evorpacept, has shown promising activity and a favorable tolerability profile when combined with various anti-cancer antibodies and other treatments.

The company's strategy focuses on combining evorpacept with standard-of-care agents, including anti-cancer antibodies and PD-1/PD-L1 immune checkpoint inhibitors. Evorpacept's rational design, featuring an inactive Fc effector function, has resulted in a superior safety profile compared to other anti-CD47 molecules in clinical trials. This allows for higher dosages with minimal overlapping toxicity in combination treatments.

The ongoing Phase 1/2 IST is an open-label, single-arm clinical trial aimed at evaluating the safety, tolerability, and efficacy of evorpacept in combination with R2 for R/R B-cell NHL. The trial is currently enrolling patients for the Phase 2 portion, focusing on untreated indolent B-NHL.

In summary, the clinical trial results for evorpacept in combination with R2 present a significant advancement in the treatment of R/R B-NHL, offering a new avenue for patients who have seen their disease progress after initial treatments. The data supports the continued exploration and development of evorpacept as a potential new therapy in the fight against NHL.