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Drug-induced interstitial lung disease (DILD) has already been paid more and more attention, especially for targeted agents and newer generation antibody-drug conjugates (ADC). DILD is a common pulmonary toxicity and may be lethal to the patients, requiring early diagnosis and intervention. No symptom or no specific symptoms make the diagnosis difficult, and periodic CT monitoring should be performed in the clinical practice. Early use of Fudan University Shanghai Cancer Center criteria for management of targeted drug-induced interstitial lung disease in solid tumors can reverse the poor prognosis of this drug-related toxicity.

Background: Senaparib, a novel poly(ADP-ribose) polymerase 1/2 inhibitor, demonstrated antitumor activity in preclinical studies. This phase I, first-in-human, dose-escalation/-expansion study explored the pharmacokinetics, safety and tolerability, and preliminary antitumor activity of senaparib in Chinese patients with advanced solid tumors. Patients and Methods: Adults with advanced solid tumors who had failed ³1 line of prior systemic treatment were enrolled. Senaparib (once daily [QD]) dose was escalated from 2 mg until the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) using a modified 3 + 3 design. Dose expansion included: dose groups with ≥1 objective response and one dose higher, as well as those at the MTD/RP2D. Primary objectives were to evaluate the safety and tolerability, and determine the MTD and/or RP2D of senaparib. Results: Fifty-seven patients were enrolled across 10 dose groups (2-120 mg QD, and 50 mg twice daily). No dose-limiting toxicities were observed. The most common senaparib-related adverse events were anemia (80.9%), white blood cell count decreased (43.9%), platelet count decreased (28.1%), and asthenia (26.3%). Senaparib exposure increased dose proportionately at 2-80 mg; absorption saturated at 80-120 mg. Senaparib accumulation was minimal after repeated QD administration (accumulation ratio=1.1-1.5). The objective response rate was 22.7% (n=10/44) overall (all partial responses) and 26.9% (n=7/26) for patients harboring BRCA1/BRCA2 mutations. Disease control rates were 63.6% and 73.1%, respectively. Conclusions: Senaparib was well tolerated and demonstrated promising antitumor activity in Chinese patients with advanced solid tumors. The RP2D for this clinical study in China was identified as 100 mg QD. ClinicalTrials.gov Identifier: NCT03508011 This phase I, first-in-human, dose-escalation/-expansion study explored the pharmacokinetics, safety, and tolerability, and preliminary antitumor activity of senaparib in Chinese patients with advanced solid tumors. [ABSTRACT FROM AUTHOR]

Serologic biomarker to predict clinical outcome is needed for immune checkpoint inhibitors (ICIs). We evaluated soluble intercellular adhesion molecules‐1 (sICAM‐1) as a predictor of response to ICIs treatment. Ninety‐five patients with cancer treated with ICI were studied. The serum sICAM‐1 levels of baseline, post two cycle therapy and end of therapy (EOT) were measured by enzyme‐linked immunoassay. We randomly assigned the patients into the primary cohort (n = 47) and validation cohort (n = 48). Serum sICAM‐1 post two cycle (277.7 ± 181.6 ng/mL) and EOT (403.9 ± 218.9 ng/mL) were significantly elevated compared to baseline (244.8 ± 153.8 ng/mL, p = 0.008 and p = 0.004, respectively). Early changes of sICAM‐1 (ΔsICAM‐1), deemed as sICAM‐1 after two cycles minus baseline, were assessed. Following ICI treatments, responders had significantly lower ΔsICAM‐1 compared with nonresponders in the primary cohort (p = 0.040) and the validation cohort (p = 0.026). High ΔsICAM‐1 was strongly associated with inferior progression‐free survival (PFS; (primary cohort: p = 0.001 and validation cohort: p = 0.002) and overall survival (OS; (primary cohort: p < 0.001 and validation cohort: p = 0.007). The ΔsICAM‐1 remained independently associated with worse PFS and OS in the primary cohort and the validation cohort. Subgroup analysis indicated patients whose sICAM‐1 significantly elevated had shorter PFS and OS in both anti‐PD‐1 and anti‐PD‐L1 treatment groups. Early change of serum sICAM‐1 could be used to monitor and predict clinical benefit of ICI therapy in patients with solid cancer. [ABSTRACT FROM AUTHOR]

Background and objective: The development of epigenetics holds great promise for diagnosis and treatment of lung adenocarcinoma (LUAD). The purpose of this work was to analyze the correlation between Ras Homolog Gene Family Member H (RHOH) expression and methylation in patients with LUAD and its association with survival. Methods: Data related to gene expression, DNA methylation, and clinical features of LUAD from The Cancer Genome Atlas (TCGA) database were analyzed. A total of 50 patients were included in verification group. The methylation level of RHOH in verification group was detected by bisulfite amplicon sequencing. Results: The RHOH methylation level in TCGA cohort was significantly and negatively correlated with its expression level (Cor = −0.5, p = 2.687e−33). Patients with hypermethylation and low expression of RHOH had significantly worse prognosis than patients with hypomethylation and low expression of RHOH (TCGA: p = 0.004; validation cohort: p = 0.006, HR: 4.740, 95% CI: 1.567–14.340). Conclusion: Our research revealed that RHOH may prove to be a new potential prognostic predictor for LUAD patients. [ABSTRACT FROM AUTHOR]

Background. This single-arm, nonrandomized, open-label, dose-escalation, phase I study was designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of ramucirumab in Chinese patients with advanced solid tumors that were resistant to standard therapy or no standard therapy was available. Methods. Dose escalation was a 31 3 design, with expansion in Cohorts 2 and 3 for PK. Ramucirumab was given intravenously at three different dosages: 6 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, and 8 mg/kg every 2 weeks. Safety analyses included all patients. PK, immunogenicity, and antitumor activity were also assessed. Results. Among 28 patients treated, 2 experienced dose-limiting toxicity, possibly related to ramucirumab. No maximum tolerated dose was determined. All patients experienced at least one treatment-emergent adverse event. Grade ≥3 adverse event was reported for 53.6% (n 5 15) of patients. PK analyses indicated that ramucirumab had low clearance, small volume of distribution, and long half-life in Chinese patients, as in other populations. Immunogenicity was not detected. No patient had complete/partial response, and 64.3% (n 5 18) had stable disease with a median duration of 5.55 months (95% confidence interval: 3.38-7.13 months). Conclusion. Ramucirumab appeared to be well tolerated in Chinese patients with advanced solid tumors. PK characteristics in Chinese patients were similar to those in other populations. [ABSTRACT FROM AUTHOR]

Abstract: We present the theoretical foundation, design, and implementation, of a system that automatically determines the subset relation between two given axiomatizations of propositional modal logics. This is an open problem for automated theorem proving. Our system solves all but six out of 121 instances formed from 11 common axiomatizations of seven modal logics. Thus, although the problem is undecidable in general, our approach is empirically successful in practically relevant situations. [Copyright &y& Elsevier]