felzartamab (MOR202)

P3, N=120, Not yet recruiting, HI-Bio, A Biogen Company

P1, N=20, Recruiting, HI-Bio | Trial completion date: May 2025 --> Jun 2026 | Trial primary completion date: May 2025 --> Jun 2026

P1, N=24, Completed, TJ Biopharma Co., Ltd. | Recruiting --> Completed | N=60 --> 24 | Trial completion date: Dec 2024 --> Aug 2024 | Trial primary completion date: Dec 2024 --> Aug 2024

P3, N=289, Completed, TJ Biopharma Co., Ltd. | Active, not recruiting --> Completed

P2, N=22, Completed, Farsad Eskandary | Active, not recruiting --> Completed

P1, N=60, Not yet recruiting, I-Mab Biopharma Co. Ltd.

P2, N=113, Active, not recruiting, I-Mab Biopharma Co. Ltd. | Trial completion date: Dec 2023 --> Dec 2024

Despite the overall significant response rates to these therapies-particularly rituximab and cyclical regimen based on corticosteroids and cyclophosphamide-cumulative experience over the years has shown, however, that 20%-30% of cases may confront resistant disease...Among the different novel therapies, newer anti-CD20 agents (e.g. obinutuzumab), anti-CD38 (e.g. daratumumab, felzartamab), immunoadsorption or anti-complement therapies (e.g. iptacopan) have gained special attention. In addition, several technologies and innovations developed primarily for cancer (e.g. chimeric antigen receptor T-cell therapy, sweeping antibodies) seem particularly promising. In summary, the future therapeutic landscape in MN seems encouraging and will definitely move the management of this disease towards a more precision-based approach.

Combination of lemzoparlimab and felzartamab showed enhanced in vitro ADCP and in vivo anti-tumor efficacy in these CD47 high and CD38 low high-risk MM cells which were resistant to felzartamab or daratumumab mono-treatment. Our study provides preclinical evidence to explore the combination of lemzoparlimab and felzartamab in the treatment of high-risk MM patients.

Daratumumab and isatuximab already received FDA approval, and novel agents such as MOR202, TAK079 and TNB-738 undergo clinical trials. Also, novel therapeutics such as SAR442085 aim to outrank the older antibodies against CD38...This review focuses on targeting CD38 in cancer and non-cancerous diseases using antibodies, cell-based therapies and CD38 inhibitors. We also provide a summary of current clinical trials targeting CD38.

At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab ("Pom-PAD-Dara"), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM.

Daratumumab (Dara), a CD38-targeting antibody, can eliminate CD38 immune suppressor cells and is regarded as a standard therapy for MM because of its outstanding clinical efficacy. Other CD38 monospecific antibodies, such as isatuximab, MOR202, and TAK079, showed promising effects in clinical trials...There is convincing evidence that CD38-targeted immunotherapeutics reduce CD38 immune suppressor cells. This result suggests that CD38 can be exploited to treat solid tumors by regulating the immunosuppressive microenvironment.