ALX Oncology Begins Dosing Evorpacept and Sarclisa in Phase 1/2 UMBRELLA Study with Sanofi

ALX Oncology Holdings Inc., a company specializing in immuno-oncology, has announced the first dosing of patients in a new clinical study for multiple myeloma. This study, in collaboration with Sanofi, is part of the randomized UMBRELLA phase 1/2 clinical trial. The trial is designed to evaluate the effectiveness of a novel treatment combination: ALX Oncology’s investigational CD47-blocking therapeutic, evorpacept, and Sanofi’s approved CD38 monoclonal antibody, SARCLISA® (isatuximab-irfc).

Multiple myeloma (MM) is a type of blood cancer that affects plasma cells in the bone marrow. Despite various treatments, MM remains incurable and patients often relapse or become refractory to current therapies. SARCLISA works by targeting a specific epitope on the CD38 receptor on MM cells, thereby inducing anti-tumor activity. However, some patients develop resistance to CD38-targeting agents after initial treatment. As MM progresses, CD47 expression increases, potentially contributing to this resistance. Evorpacept, which targets CD47, may help re-sensitize tumors to CD38 treatment or overcome existing resistance.

The UMBRELLA study aims to explore the synergistic potential of combining evorpacept with SARCLISA and dexamethasone. The trial will be conducted by Sanofi and is divided into two parts. The first part focuses on determining the appropriate dose of evorpacept when used with standard doses of SARCLISA and dexamethasone. The second part will assess the safety and effectiveness of this combination in a broader patient population with relapsed or refractory MM (RRMM).

Sophia Randolph, M.D., Ph.D., Chief Medical Officer at ALX Oncology, highlighted the urgent need for innovative treatments in multiple myeloma. She expressed optimism about the potential of the therapeutic combination being tested in the UMBRELLA study to improve patient outcomes. Randolph underscored the significance of evorpacept’s ability to enhance anti-cancer activity while maintaining a favorable safety profile across different cancer types.

Sanofi's Global Head of Oncology Development, Peter C. Adamson, M.D., echoed these sentiments. He noted that SARCLISA could be an excellent partner for novel agents like evorpacept. The partnership with ALX Oncology aims to explore synergistic combinations to tackle therapeutic challenges faced by RRMM patients.

Globally, multiple myeloma is the second most common hematologic malignancy, with over 185,000 new cases diagnosed each year. In the United States alone, there are more than 35,000 new diagnoses annually. Despite existing treatments, MM remains an incurable disease, leading to significant patient burden. Most patients experience relapse, and some become refractory to treatment, making new therapeutic options critically important.

ALX Oncology is dedicated to developing therapies that block the CD47 immune checkpoint pathway, thus helping patients combat cancer. The company's lead product, evorpacept, combines a high-affinity CD47-binding domain with an inactivated Fc domain. To date, evorpacept has shown promising activity and a favorable safety profile in over 500 patients, covering a range of hematologic and solid cancers. ALX Oncology’s strategy involves combining evorpacept with various anti-cancer antibodies, antibody-drug conjugates (ADCs), and PD-1/PD-L1 immune checkpoint inhibitors to enhance treatment efficacy.

Evorpacept’s unique design includes an inactive Fc effector function, which substantially improves its safety profile compared to other anti-CD47 molecules. This allows for higher dosages with minimal overlapping toxicity. By blocking the CD47-SIRP alpha interaction, evorpacept enables the immune system to better target cancer cells. 

SARCLISA, approved in over 50 countries, is designed to combat multiple myeloma through multiple mechanisms, including programmed cell death and immunomodulation. Currently, it is approved in combination with other drugs for patients with RRMM who have undergone prior treatments. SARCLISA continues to be evaluated in phase 3 clinical studies and is also being investigated for other hematologic malignancies. 

In summary, the collaboration between ALX Oncology and Sanofi through the UMBRELLA clinical trial represents a significant step forward in the treatment of multiple myeloma, offering hope for improved patient outcomes in this challenging disease.

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