AstraZeneca Launches Phase 3 Trials in China for Three Antibody Therapies Targeting NSCLC and Lupus Nephritis

Source | Pharmaceutical Viewpoint

On June 20, the China Drug Clinical Trial Registration and Information Disclosure Platform showed that AstraZeneca had launched Phase 3 clinical trials in China for three new antibody drugs: the anti-CD73 antibody oleclumab, the anti-NKG2A antibody monalizumab, and the new antibody drug targeting type I interferon receptor, anifrolumab. The indications involved include specific non-small cell lung cancer and adult patients with active lupus nephritis.

Screenshot source: Drug Clinical Trial Registration and Information Disclosure Platform

Drug Name: oleclumab, monalizumab

Mechanism of Action: Anti-CD73 Antibody, Anti-NKG2A Antibody

Indications: Non-Small Cell Lung Cancer (NSCLC)

Oleclumab is a potential "first-in-class" anti-CD73 monoclonal antibody developed by AstraZeneca. CD73 is the rate-limiting enzyme that catalyzes the conversion of adenosine monophosphate (AMP) to adenosine, and the adenosine pathway it mediates is one of the key inhibitory factors of innate and adaptive immunity in the tumor microenvironment. Oleclumab selectively binds to and inhibits the activity of CD73 to achieve therapeutic effects against tumors.

Public information shows that monalizumab, a potential "first-in-class" anti-NKG2A antibody, is being co-developed by AstraZeneca and Innate Pharma. It has high specificity for human NKG2A. In in vitro studies, this antibody demonstrated the expected effects, significantly enhancing the anti-tumor capabilities of T cells and natural killer cells.

According to the Chinese Clinical Trial Registry and Information Disclosure Platform, AstraZeneca has registered a randomized, double-blind, placebo-controlled international multicenter (including China) Phase 3 study (PACIFIC-9). This study aims to evaluate the efficacy and safety of durvalumab + oleclumab and durvalumab + monalizumab in patients with locally advanced (Stage III), unresectable NSCLC who have not progressed after radical platinum-based concurrent chemoradiotherapy. The study plans to recruit 170 participants in China.

At the 2021 European Society for Medical Oncology (ESMO) Annual Meeting, AstraZeneca presented the interim analysis results of a phase 2 clinical trial evaluating two combination therapies for patients with locally advanced, unresectable stage III non-small cell lung cancer. The data showed that at a median follow-up time of 11.5 months, compared with durvalumab monotherapy, the combination of durvalumab and oleclumab reduced the risk of disease progression or death by 56%, while the combination of durvalumab and monalizumab reduced the risk of disease progression or death by 35%. Additionally, in terms of progression-free survival rates, both combination therapy groups were higher than the durvalumab monotherapy group.

Drug Name: anifrolumab

Mechanism of Action: Antibody Targeting Type I Interferon Receptor

Indications: Active Lupus Nephritis

Public information shows that anifrolumab is a monoclonal antibody that inhibits the type I interferon signaling pathway. Type I interferons are cytokines involved in inflammatory responses, and anifrolumab can bind to subunit 1 of the type I interferon receptor, thereby antagonizing activities related to type I interferons (IFN-α, IFN-β, and IFN-ω). In August 2021, the drug received approval from the U.S. FDA for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE). In China, anifrolumab has also been approved to conduct clinical studies for treating systemic lupus erythematosus and active lupus nephritis, respectively.

According to the Chinese Drug Clinical Trial Registry and Information Disclosure Platform, AstraZeneca has registered a randomized, double-blind, placebo-controlled international multicenter (including China) Phase 3 clinical trial. This study aims to evaluate the efficacy and safety of anifrolumab in adult patients with active lupus nephritis. The trial plans to enroll 64 patients in China.

In February 2022, researchers announced the Phase 2 clinical data of anifrolumab for the treatment of active lupus nephritis. In this study, 147 patients were randomly assigned (1:1:1) to receive either the basic regimen of anifrolumab, the intensive regimen of anifrolumab, or a placebo.

Screenshot source: Reference [3]

Trial data showed that: at week 52, the 24-hour urine protein/creatinine ratio (UPCR) increased by 69% in the anifrolumab group and 70% in the placebo group; the serum concentration was higher in the anifrolumab enhanced regimen group compared to the anifrolumab base regimen group; more patients receiving the anifrolumab enhanced regimen achieved complete renal response (CRR, 45.5% vs 31.1%) compared to the placebo group; the incidence of serious adverse events was similar across groups.

References:

[1] China Drug Clinical Trial Registration and Information Disclosure Platform. Retrieved June 21, 2022, from http://www.chinadrugtrials.org.cn/index.html

[2]Imfinzicombinedwithnovelimmunotherapiesimprovedclinicaloutcomesforpatientswithunresectable,StageIIInon-smallcelllungcancer.RetrievedSep17,2021,from https://www.astrazeneca.com/media-centre/press-releases/2021/imfinzi-combined-with-novel-immunotherapies-improved-clinical-outcomes-for-patients-with-unresectable-stage-iii-non-small-cell-lung-cancer.html

[3]Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Retrieved Feb 10，2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921596/#:~:text=Anifrolumab%20targets%20the%20type%20I%20interferon%20signalling%20pathway%2C,an%20interferon-targeted%20therapy%20in%20patients%20with%20active%20LN.

Original Title: AstraZeneca Launches Phase 3 Clinical Trials in China for 3 New Antibody Drugs, Targeting Non-Small Cell Lung Cancer and Other Indications!

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