No treatment-related adverse events (TRAEs) led to death. The most common reason for discontinuation (dc) in all groups was disease progression.
Disease control rates (DCR = CR+PR+SD) were 41% for Mono10 (n = 47 of 114; 10 PRs) and 37% for Combo (n = 10 of 27; 1CR + 4 PRs (1CR and 3PRs at 3 mg/kg IPI [IPI3]).
|Mono10 ≥6M-TD (n = 28)||Combo ≥6M-TD (n = 6)|
|Median follow-up (wk)||14.5||46.4||13.0||83.6|
|Median age (y)/no. prior treatments||60/2||60/2||56/3||55/4|
|PD-L1+ expression (%)||42||54||24||17|
|ECOG PS 0 (%)||33||57||43||33|
|Grade ≥3 TRAEs (%)||9||14||33||33|
|G3+ irAEs (%)||3||0||29||0|
|Treatment related serious AEs (%)||5||7||33||17|
|TRAEs leading to dc (%)||2||0||19||0|
CX-072 monotherapy demonstrated durable responses consistent with activation of the PROBODY therapeutic in the TME. The safety profile supports the tolerability of CX-072 as monotherapy and when combined with IPI3. CX-072 + IPI3 demonstrated activity in heavily pretreated pts with various tumors. The safety profile of the combination of CX-072 with IPI3 compares favorably to historical data (grade ≥3 TRAEs 55% and leading to dc in 36%; Larkin J, et al. N Engl J Med. 2015;373:23-34). CX-072 + IPI3 is being explored in a phase 2 study in 2L melanoma.
Monotherapy with immune checkpoint inhibitors (ICIs) has demonstrated efficacy in many cancers. Combining ICIs PD-L1 + CTLA-4 enhanced efficacy but worsened toxicity vs monotherapy; therefore, CTLA-4 dose modifications are often needed, despite a dose-response effect having been shown for efficacy. CX-072 is an investigational PD-L1 PROBODY therapeutic that is preferentially activated in the tumor microenvironment (TME); localized activation may reduce immune-related AEs (irAEs). PROCLAIM-CX-072-001 identified 10 mg/kg Q2W (Mono10) as the recommended monotherapy dose. Here we provide data for Mono10 and for dose escalation of CX-072 in combination with IPI (Combo), with a focus on long-term (≥6 mo) therapy.