Study design
NSCLC, SCLC, nausea, DLTs, bleeding, tumor, fatigue, NPC, toxicities, thrombocytopenia, CRC, small cell lung cancer, PD, HCC
DISEASE PROGRESSION, BLEEDING, TUMOR, SCLC, FEBRILE NEUTROPENIA, THROMBOCYTOPENIA, SOLID TUMORS, NASOPHARYNGEAL CARCINOMA, MALIGNANCIES, CERVICAL CANCER, NSCLC
This phase I/Ib, open-label, multicenter study consisted of a phase I study and a phase Ib study in patients with advanced solid tumors performed in 41 Grade A class 3 hospitals in China. Phase I was a dose escalation and expansion study. In the dose-escalation stage, accelerated titration (0.3 mg/kg) combined with the standard 3 + 3 design was adopted. The PK expansion stage planned to include 5–9 cases in selected cohorts. Five dose levels of QL1706 (0.3, 1.0, 3.0, 5.0, and 10.0 mg/kg) were administered every 3 weeks via intravenous infusion. The initial dose was determined by the minimum anticipated biologic effect level, the no-observed-adverse-effect level, and the preclinical data. Dose-limiting toxicities (DLTs) were evaluated in each cohort based on the QL1706-related AEs occurring within 21 days (1 cycle) after the administration of the first dose, which were defined as follows: grade 1, 3–5 nonhematologic AEs (G3 vomiting or nausea alleviated within 72 h and G3 fatigue were excluded); grade 2, 4–5 hematologic AEs; grade 3, thrombocytopenia with the symptom of bleeding; grade 4, febrile neutropenia; grade 5, any AEs leading to new treatment with steroids. Once the maximum tolerated dose (MTD) or maximum administered dose were reached, additional eligible patients were enrolled in the dose-expansion stage of phase I and treated with two dose levels of QL1706 chosen by the investigators to provide further evidence to establish the RP2D. The primary objectives of phase I were to determine the safety, tolerability (DLT and MTD), and RP2D of QL1706. Secondary objectives included immunogenicity, PK, and PD of QL1706.In phase Ib, QL1706 was administered at the RP2D intravenously once every 3 weeks in patients with NSCLC, nasopharyngeal carcinoma (NPC), cervical cancer (CC), CRC, small cell lung cancer (SCLC), HCC, and other solid tumors. In principle, no fewer than 20 patients were included per tumor type, and the number of patients enrolled with each tumor type was adjusted in a timely manner based on the efficacy and safety results found during the research. The primary objective of phase Ib was to evaluate the preliminary efficacy of QL1706 in certain malignancies (NSCLC, NPC, CC, CRC, etc.) at the RP2D. Secondary objectives included safety and population-PK.Each subject received QL1706 at only one dose level. A subject could be discontinued from the study for any of the following reasons: disease progression (unless the investigators believed that there was a continuous clinical benefit), study completion (up to 2 years), development of intolerable AEs, initiation of a new antitumor treatment, or informed consent withdrawal, whichever came first.The study protocol and all amendments were approved by the Institutional Review Board of all participating institutions. All participants provided written informed consent. The study was done in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. This trial was registered at ClinicalTrials.gov (identifier: NCT04296994 and NCT05171790).