pinatuzumab vedotin (RG7593)

In 5 trials (N=204), 13 patients with Pola + atezolizumab (Ate) + obinutuzumab (Obi), 49 patients with Pola + Obi + venetoclax (Ven), 39 patients with Pola + Obi, 62 with Pola + Obi + lenalidomide (Len), and 20 patients with Pola + rituximab (Rit)...(N=41), Pola + Rit was compared with pinatuzumab vedotin (Pina) + Rit... Pola was well tolerated by most of the patients with FL alone or in combination with Obi, Rit, Len, Ven. Pola had relatively better response and survival rates as compared to Pina in combination with Rit. In early phase clinical trials, three drug regimens of Pola and Obi with Ven, and Len were effective in the treatment of heavily pretreated follicular lymphoma.

We are interested in developing a second generation of antibody-drug conjugates (ADCs) for the treatment of non-Hodgkin's lymphoma (NHL) that could provide a longer duration of response and be more effective in indolent NHL than the microtubule inhibiting ADCs pinatuzumab vedotin (anti-CD22-vc-MMAE) and polatuzumab vedotin (anti-CD79b-vc-MMAE). We found that anti-CD22-(LC:K149C)-SN36248 was effective in xenograft models resistant to pinatuzumab vedotin, gave a longer duration of response, had a different mechanism of resistance and was able to deplete normal B cells better than pinatuzumab vedotin. These studies provide evidence that anti-CD22-(LC:K149C)-SN36248 has the potential for longer duration of response and more efficacy in indolent NHL than MMAE ADCs and may provide the opportunity to improve outcomes for NHL patients.