This year ASCO's new PD-L1 antibody data code-named CX-072 was released, from the results of the study, its safety is excellent, more intimate is the target PD-L1 precursor treatment drug CX-072 "instruction" also appeared in the ASCO wall report, then we have a good understanding of this post-riseIn phase I/II trials, evidence of intratumor localization, activation, and immunomodulation of the precursor therapy drug CX-072 targeted at PD-L1BACKGROUND: PROBODY Therapy (Pb Tx) is a shielded antibody that selectively activates tumor microenvironments through tumor-related proteases and remains mostly inactive in normal tissuesThe CX-072 is APb-Tx for PD-L1 and is designed to reduce the likelihood of immune-related adverse events in normal tissues while maintaining antitumor activityThe CX-072 is under study in THE PR-CX-072 (NCT03013491), the first human phase I/II trialCX-072 is given to patients with metastatic or recurrent solid or lymphomas with single drugs or in combination with epipimo, who do not have approved treatment based on PD-1 / -L1We provide the latest results of tissue-based biomarker studies designed to assess the activation, positioning and action mechanisms of CX-072 in patient tumorsMethods: Tumor biopsies were collected 3 to 5 days after the screening stage and the first or third dose of 0.3 to 30 mg / kg CX-072Tumor-related protease activity was determined by tissue enzyme spectrometryThe activation of CX-072 in the tumor was measured using capillary immunoradiosis and the level of PD-L1 was measured with ultra-sensitive ELISAUse immunohistochemical analysis of cd8 expression in tumorsThe complete total CX-072 in the plasma is measured by LC-MS/MSResults: In 30 assessable pre-drug biopsies, 26 (87%) had detectable levels of associated protease activityIntra-tumor activation of CX-072 can be quantified in 3 of 8 biopsies (38%) (treated at 3 mg/kg dose) and 12 (100%) biopsies (treated at 10 mg/kg)In contrast, the CX-072 remains in full form in the loopThe muryl ratio of CX-072 in tumors activated in patients with a dose of 10 mg / kg was in the range of ?14x to 100x, and the calculated tumor receptor occupancy of these patients was 99%, consistent with quantitative system pharmacology model prediction The increase in CD8 plus was consistent with the inhibition of the PD-L1 pathway in 11 (61%) tumors in 18 cases of CX-072 single drug treatment Conclusion: These results show that Pb Tx CX-072 performed in patients in line with the design PL-CX-072: Analysis of patients with advanced solid tumors who received PD-L1 antibody precursor therapy drug CX-072 as a single drug or in combination with ipilimumab BACKGROUND: Single therapy for immunocheckpoint inhibitors (ICIs) has been shown to be effective in many cancers The combined use of ICIs PD-L1 and CTLA-4 is more effective but more toxic than single-drug therapy, and therefore, despite the dose-response effects of the drug, ctLA-4 doses are often adjusted CX-072 is a research PD-L1 antibody therapy that can be activated first in tumor microenvironments (TME); THE EPS-CX-072-001 IDENTIFIED 10 MG / KG Q2W (Mono10) as the recommended single therapy dose Here, we provide data on the increasing dose of Mono10 and CX-072 combined with IPI (Combo), with a focus on long-term treatment Methods: Mono10 was evaluated in a variety of tumor types The combined dose of Q3W assessment is CX-072 0.3 to 10 mg / kg and IPI 3 to 10 mg / kg Compare patients with treatment duration of 6 mo (-6M-TD) as of November 30, 2019 Results: The disease control rate (DCR-CR-PR-SD) mono10 was 41% (n-47/114; 10 PRs) and Combo were 37% (n-10/27; 1CR-4 PRs (1CR/kg IPI at 1CR and 3P (IPI3)
The RESULTs of the PL-CX-072 study did not result in death from adverse events (TRAE) associated with treatment The most common stop-and-go (dc) cause in all groups was disease progression Conclusion : CX-072 monotherapy showed a long-lasting response, consistent with the activation of PROBODY therapy in TME The safety profile supports CX-072 as a monotherapy and tolerance when combined with IPI3 CX-072 plus IPI3 showed activity in highly pretreated patients with multiple tumors The CX-072 and IPI3 combinations are more secure than historical data (the ratio of a rating of 3 is 55%, resulting in 36% dc) Author: Ren Ran Source: Health
