PROCLAIM-001: A first-in-human trial to assess tolerability of the protease-activatable anti-PD-L1 Probody CX-072 in solid tumors and lymphomas.

TPS3107 Background: CX-072 is a novel Probody™ therapeutic (PbTx) targeting PD-L1. PbTx’s are fully recombinant antibody prodrugs designed to be converted to active antibodies by tumor-associated proteases that are highly expressed malignant tissue; the PbTx remains largely inactive in normal tissues. In pre-clinical tumor models, a PD-L1-directed PbTx provided comparable anti-tumor efficacy to its parental anti-PD-L1 antibody, but displayed reduced auto-immunity in a model of Type 1 diabetes. Based on these pre-clinical data, CX-072 has the potential to enable combination therapies that are otherwise poorly tolerated. This Phase 1/2 study (PROCLAIM-001 (PRObody CLinical Assessment In Man) assesses the tolerability and antitumor activity of CX-072 in humans with an emphasis on immune-related adverse events, particularly in combinations. CX-072 will be administered as monotherapy (Part A), in combination with 2 schedules of ipilimumab (Parts B1 and B2) and in combination with vemurafenib (Part C). The expansion cohort (Part D) will include CX-072 monotherapy in PD-L1 responsive tumor types. Methods: Key eligibility criteria are as follows: Parts A and B1: checkpoint inhibitor-naive patients with advanced, refractory solid tumor or lymphoma (unmeasurable disease allowed) for whom approved PD agents are not available. Part B2: advanced, refractory solid tumors or lymphomas with measurable disease who have progressed on a previous treatment with a PD-(L)1 inhibitor, but did not discontinue due to toxicity. Part C: checkpoint inhibitor, BRAF-inhibitor and MEK-inhibitor-naïve metastatic V600E BRAF-mutated melanoma. Patients without an active autoimmune disease, ongoing infection, and ECOG PS 0-1 may be eligible to participate in the study. Dose escalation follows the 3+3 design in all arms. Ipilimumab (Parts B1 and B2) is dosed at the approved 3 mg/kg every 3 weeks x 4. The dose of vemurafenib (Part C) is 960 mg/kg twice daily. Exploratory biomarkers are used to characterize tumor protease activity, inflammatory changes within the tumor, and CX-072 activation in tumor versus peripheral blood. Clinical trial information: NCT03013491.