CB307

This Phase I study investigated the safety and tolerability of CB307 as monotherapy or with pembrolizumab. In a post-hoc analysis, the response was numerically better in patients who had not received chemotherapy in the 6 months prior to starting CB307 (ORR = 20%, DCR 60% vs. ORR 0%, DCR 37.5%). CB307 induces cytotoxic cell expansion in tumors and PD-L1 expression.

P1, N=5, Active, not recruiting, Crescendo Biologics Ltd. | Recruiting --> Active, not recruiting | N=12 --> 5 | Trial completion date: Dec 2023 --> Oct 2024

P1, N=70, Recruiting, Crescendo Biologics Ltd. | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Jul 2023 --> Jul 2024

CB307 or PD-1/PD-L1 inhibition alone induced IL-2 secretion in PBMC/PSMA-expressing tumor cell cocultures; this effect was synergistically enhanced when CB307 was combined with either PD-1 or PD-L1 inhibition. CB307 augmented tumor cell killing in 3D spheroids containing PSMA-expressing cells. Enhanced tumor cell killing was observed in spheroid cultures containing CB307 in combination with PD-1/PD-L1 inhibition.

In reporter assays and PBMC cocultures, CB307 activated CD137 only in the presence of PSMA-expressing cells leading to enhanced immune cell activation. Enzalutamide pre-treatment of 22Rv1 (PSMA-low) cells induced a 1.5-fold increase in surface PSMA expression leading to enhanced CB307 activity. CB307 or PD1/PDL1 inhibition alone induced IL-2 secretion in PBMC/PSMA-expressing tumor cell cocultures; this effect was synergistically enhanced when CB307 was combined with either PD1 or PDL1 inhibition.