AstraZeneca and Forty Seven Announce Clinical Collaboration to Evaluate Anti-CD47 Antibody-Based Triple Combination Therapy in Diffuse Large B-Cell Lymphoma

Recently, clinical-stage oncology immunotherapy company Forty Seven announced a clinical trial collaboration with Acerta Pharma, an affiliate of AstraZeneca, to evaluate the efficacy of a triple-combination therapy in diffuse large B-cell lymphoma (DLBCL). This innovative regimen comprises the anti-CD47 monoclonal antibody 5F9, rituximab, and the targeted Bruton’s tyrosine kinase (BTK) inhibitor Calquence (acalabrutinib).

Non-Hodgkin lymphoma is currently the most common hematologic malignancy, resulting from the malignant transformation of lymphocytes. Among these, more than 85% are B-cell lymphomas. Diffuse large B-cell lymphoma is the most common aggressive subtype.

Forty Seven, Inc. is dedicated to developing innovative therapies that target cancer immune evasion pathways. Its investigational monoclonal antibody, 5F9, specifically binds to CD47, the “don’t eat me” signal overexpressed on the surface of tumor cells, thereby restoring the ability of macrophages to phagocytose tumor cells. Currently, the efficacy of this antibody is being evaluated in multiple clinical trials across solid tumors, acute myeloid leukemia, non-Hodgkin lymphoma, ovarian cancer, and colorectal cancer.

▲Hu5F9-G4 can block CD47 from sending the “don’t eat me” signal and release and promote the “eat me” signal (Image source: Forty Seven official website)

A Phase 1b Clinical Trial Announced Not Long AgoResearch Resultsdemonstrated that 5F9 in combination with rituximab showed positive outcomes in the treatment of patients with relapsed/refractory DLBCL and follicular lymphoma.

AstraZeneca’s Calquence (acalabrutinib) is a highly selective Bruton’s tyrosine kinase (BTK) inhibitor. In B lymphocytes, the BTK-mediated signaling pathway is essential for stimulating B-cell proliferation, trafficking, chemotaxis, and adhesion. Calquence inhibits BTK activity through covalent binding. A recently completed Phase 3 clinical trial demonstrated that Calquence, as monotherapy, in the treatment of patients with relapsed/refractory chronic lymphocytic leukemiaSignificantly Superior to Standard Therapy。

“BTK inhibitors have already demonstrated therapeutic potential in patients with B-cell lymphoma. We believe that simultaneously activating macrophages within the innate immune system can yield greater benefits than either approach used alone,” said Dr. Craig Gibbs, Chief Business Officer of Forty Seven, Inc., upon announcing the collaboration. “The triple-combination therapy we are striving to advance is designed specifically to meet the needs of patients with diffuse large B-cell lymphoma (DLBCL).”

References

[1] Forty Seven Inc. and Acerta Enter Collaboration to Evaluate Novel Immuno-Oncology Triple Combination in Diffuse Large B-cell Lymphoma. Retrieved May 12, 2019, from http://www.globenewswire.com/news-release/2019/05/10/1821791/0/en/Forty-Seven-Inc-and-Acerta-Enter-Collaboration-to-Evaluate-Novel-Immuno-Oncology-Triple-Combination-in-Diffuse-Large-B-cell-Lymphoma.html

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