camsirubicin (MNPR-201)

P1, N=21, Recruiting, Monopar Therapeutics | Phase classification: P1b --> P1 | Trial primary completion date: Jun 2023 --> Jun 2025

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of aggressive lymphoma, for which the standard-of-care treatment is rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)...For example, a clear antagonistic effect on cell killing was seen between PLK1 inhibitor, volasertib, and doxorubicin, but between volasertib and MNPR-202, this antagonism was seen to a significantly lesser extent...These intracellular differences also influence drug synergies observed with the two chemotherapeutics, implying that in the context of certain combinatorial regimens, MNPR-202 may be superior to doxorubicin. Overall these findings suggest promise for further in vivo and clinical evaluation of MNPR-202 as a potentially effective yet non-cardiotoxic anthracycline derivative in lymphoma.

In preclinical models of TNBC, a triple combination of NGI-1, camsirubicin (a non-cardiotoxic doxorubicin analog) and PD-L1 blockade was effective in reducing tumor growth. Collectively, our findings uncover a novel strategy for targeting the immunosuppressive molecule B7-H4.