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Background: APG-1387 is a novel second mitochondrial-derived activator of caspases mimetic, small-molecule inhibitor targeting inhibitor of apoptosis proteins. We report results from two phase I trials evaluating the tolerability, safety, and antitumor activity of APG-1387 monotherapy and APG-1387 plus toripalimab [a programmed cell death 1 (PD-1) inhibitor] for advanced solid tumors., Patients and Methods: Participants aged ≥18 years who had histologically confirmed advanced solid tumors with no appropriate standard of care (or refractory to standard care) were eligible. Patients received escalating intravenous doses of APG-1387 alone or combined with fixed-dose toripalimab (240 mg every 3 weeks) in a '3 + 3' design. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) in the monotherapy trial, and recommended phase II dose (RP2D) in the combination therapy trial. Secondary endpoints included the pharmacokinetic and pharmacodynamic profiles and preliminary efficacy in both trials., Results: In the monotherapy trial, 28 subjects were enrolled and received ≥1 treatment cycle. No DLT was reported among the 28 subjects, and the MTD was not reached. One participant (3.6%) had a grade ≥3 treatment-related adverse event (TRAE) of alanine aminotransferase elevation. In efficacy analysis of 23 participants, none achieved an objective response, and the disease control rate was 21.7%. In the combination trial, 22 subjects were enrolled and included in all analyses. There was one DLT of grade 3 lipase elevation. The MTD was not reached. Four grade ≥3 TRAEs occurred in three participants (13.6%), with the most common being lipase elevation (n = 2). The RP2D was 45 mg weekly. The objective response rate was 13.6%, with complete response achieved in one subject, and the disease control rate was 54.5%., Conclusions: APG-1387 45 mg weekly plus toripalimab was well tolerated and is recommended for further study, with preliminary clinical activity observed in study participants with advanced solid tumors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

As immunotherapy makes its way into the perioperative setting, a growing number of clinical trials are expanding the evidence base for resectable non-small cell lung cancer (NSCLC) management. Identifying the optimal treatment pattern-whether it's neoadjuvant, adjuvant, or a combination of both-is a crucial next step, particularly in pinpointing which patients benefit the most. This decision-making process requires a multi-disciplinary treatment team capable of utilizing tissue and plasma genomic testing to inform therapeutic choices. Leveraging the perioperative treatment platform, it remains pivotal to integrate circulating tumor DNA (ctDNA) monitoring into clinical trial design efficiently and provide clear guidance on treatment., Competing Interests: Declaration of interests Y.-L.W reports grants and personal fees from AstraZeneca, BMS, and Pfizer and personal fees from Boehringer Ingelheim, Eli Lilly, Hengrui, MSD, Sanofi, and Roche., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC., Objectives: We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy., Design: Chemotherapy is administered and blood specimens are collected at four time points from baseline to disease progression for CTC detection., Methods: This multicenter prospective study enrolled patients with previously untreated stage III or IV NSCLC fit for standard platinum-based chemotherapy. Bloods were sampled as per standard operating procedures at baseline, cycle 1 and cycle 4 of chemotherapy, and at disease progression for CTC analysis using the CellSearch system., Results: Among 150 patients enrolled, median overall survival (OS) was 13.8, 8.4, and 7.9 months in patients with CTC - , KIT - CTC, and KIT + CTC at baseline ( p  = 0.002). Patients with persistent negative CTC (46.0%) had longer progression-free survival [5.7 months, 95% confidence interval (CI): 5.0-6.5 versus 3.0 months, 0.6-5.4; hazard ratio (HR): 0.34, 95% CI: 0.18-0.67) and OS (13.1 months, 10.9-15.3 versus 5.6 months, 4.1-7.1; HR: 0.17, 0.08-0.36) compared with patients with persistent positive CTC (10.7%), which was not impacted by chemotherapy. Chemotherapy decreased CTC from 36.0% (54/150) to 13.7% (13/95)., Conclusions: CTC persistent presence during treatment represents poor prognosis and resistance to chemotherapy in advanced NSCLC. Chemotherapy could effectively eliminate CTCs. Molecular characterization and the functionalization of CTC will be warranted for further intensive investigation., Trial Registration: NCT01740804., Competing Interests: Yi-Long Wu reports receiving speaker bureau fees from AstraZeneca, Bristol-Myers Squibb, Pfizer Inc., Roche AG, Boehringer Ingelheim, Eli Lilly & Co., Merck Sharp & Dohme, and Sanofi and research grants from AstraZeneca, Bristol-Myers Squibb, Pfizer Inc., and Roche AG. Other authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Background: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is still under investigation as adjuvant treatment for early-stage disease. Here, we performed a meta-analysis to evaluate the efficacy of adjuvant EGFR-TKI versus non-EGFR-TKI treatment in patients with completely resected non-small cell lung cancer (NSCLC) harboring EGFR mutation., Methods: Two investigators independently extracted data from databases. A meta-analysis was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered in PROSPERO (ID: CRD42022316481). The primary outcome was disease-free survival (DFS) in patients with EGFR mutation, measured as the hazard ratio (HR). Other outcomes (of subgroup analyses) included overall survival (OS) and DFS., Results: After the systematic screening, eight studies with a total of 3098 patients with stage IB-IIIA NSCLC were included. The results show that in patients with EGFR mutation, the DFS in the adjuvant EGFR-TKI group was significantly superior to that in the control group, with a HR of 0.47 (95% confidence interval [CI]: 0.30-0.74; P = 0.001). In subgroup analyses of DFS, the benefit was observed in the EGFR-TKI group versus the chemotherapy group (HR 0.50, 95% CI 0.30-0.84; P = 0.009), the EGFR-TKI combined with chemotherapy group versus the chemotherapy group (HR 0.37, 95% CI 0.16-0.85; P = 0.02), and in stage IIA-IIIA NSCLC (HR 0.45, 95% CI 0.27-0.74; P = 0.002). However, the benefit of DFS did not translate into improved OS in the whole population (HR 0.79, 95% CI 0.54-1.14; P = 0.20)., Conclusion: EGFR-TKIs prolonged DFS but not OS in patients with completely resected stage II-IIIA NSCLC harboring EGFR mutation. Longer follow-ups and new clinical trials that can result in changes in clinical practice are needed., (© 2023. The Author(s).)

The adsorption and desorption of electrolyte ions strongly modulates the carrier density or carrier type on the surface of monolayer-MoS 2 catalyst during the hydrogen evolution reaction (HER). The buildup of electrolyte ions onto the surface of monolayer MoS 2 during the HER may also result in the formation of excitons and trions, similar to those observed in gate-controlled field-effect transistor devices. Using the distinct carrier relaxation dynamics of excitons and trions of monolayer MoS 2 as sensitive descriptors, an in situ microcell-based scanning time-resolved liquid cell microscope is set up to simultaneously measure the bias-dependent exciton/trion dynamics and spatially map the catalytic activity of monolayer MoS 2 during the HER. This operando probing technique used to monitor the interplay between exciton/trion dynamics and electrocatalytic activity for two-dimensional transition metal dichalcogenides provides an excellent platform to investigate the local carrier behaviors at the atomic layer/liquid electrolyte interfaces during electrocatalytic reaction.