Squamous Cell Lung Cancer

The purpose of this study is to find out whether ZEN003694 is an effective treatment for people with advanced squamous cell lung cancer with a mutation in the NSD3 gene. ZEN003694 is a type of drug called a BET inhibitor. Researchers think ZEN003694 may help here because the drug works by blocking a group of proteins called bromodomain and extra-terminal (BET) proteins, which may counteract the effect of NSD3 on tumor growth. Blocking these proteins may slow or stop the growth of the cancer.

This is a Phase I（Ib）, open-label, single-arm clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of R01 administered orally as monotherapy twice daily (BID) in patients with advanced solid tumors, including squamous cell lung cancer, gastric cancer , and esophageal cancer. Patients with advanced squamous cell lung cancer, gastric cancer , and esophageal cancer will be enrolled. All subjects will receive oral R01 monotherapy and will undergo physical examinations, laboratory tests, radiographic tumor response assessments, biological sample collection, and safety follow-ups as specified in the protocol. The study comprises two consecutive sub-stages: a dose-bridging escalation stage (i.e., a dose escalation stage designed to bridge from the highest dose evaluated in Phase Ia) and a dose expansion stage. The dose escalation follows a classic '3+3' design at three dose levels (240, 320, and 400 mg BID). The 400 mg dose may be initiated after the Safety Review Committee (SRC) review based on safety and PK data. The primary objectives of this stage are to characterize dose-limiting toxicities (DLTs), determine the maximum tolerated dose (MTD), and establish the recommended Phase II dose (RP2D). The dose expansion stage will be conducted at the RP2D in selected indication cohorts, with a planned enrollment of at least 6 subjects per cohort (including subjects with the corresponding indications enrolled at the same dose level during the dose escalation stage), to further evaluate the safety, tolerability, PK characteristics, and preliminary antitumor efficacy at this dose level. With respect to study endpoints: during the dose escalation stage, the primary endpoints are the incidence of DLTs, the MTD, and/or the determination of the expansion dose (RP2D); secondary endpoints include PK parameters of R01 and its metabolites, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). During the dose expansion stage, the primary endpoints are ORR and the incidence and severity of treatment-related adverse events (TRAEs); secondary endpoints include duration of response (DOR), time to response (TTR), DCR, PFS, OS, and steady-state PK parameters.

This single-arm, open-label, multicenter, Phase I study will evaluate the safety, tolerability, anti-tumor activity, pharmacokinetics (PK)/pharmacodynamics (PD), biomarker, and immunogenicity of C-CAR031 in adult participants with GPC3+ advanced/metastatic squamous cell lung cancer, who are not amenable to curative therapy and have progressed or are intolerant to no more than 3 lines of prior systemic treatment including immune checkpoint inhibitors (CPIs) and platinum-based doublet chemotherapy, concurrently or sequentially.

This is a prospective, single-arm, multi-center, phase Ⅱ trial to evaluate the efficacy and safety of Polymeric Micelles paclitaxel(pm-Pac), platinum (cisplatin/carboplatin) in combination with Ivonescimab as first-line treatment in metastatic squamous NSCLC patients.

The third/fourth generation of CAR-T cells that target GPC3 (GPC3-CART cell) and/or soluble TGFβ (GPC3/TGFβ-CART )have been constructed and their anti-HCC function has been verified by multiple in vitro and in vivo studies. Clinical studies will be performed to test the anti-cancer function by the GPC3/TGFβ-CAR-T cells in human HCC patients with GPC3 expression. In this phase I study, the safety, tolerance, and preliminary efficacy of the GPC3/TGFβ-CAR-T cell immunotherapy on human will firstly be tested.

APOLLO 11 main aim is to build a strong Italian long-lasting lung cancer network (in around 48 Italian centres) on real world data and translational research by creating a decentralized long-term national database (settle locally in each centre) and a "virtual" multilevel biobank in each centre. Besides, APOLLO 11 will take advantage of the translational research joint effort with the credo "unity is strength".