Sotiburafusp alfa

This study is a multicenter, two-tumor, multi-cohort, dose-escalation and dose-expansion Phase Ib/II clinical trial of HB0025 combined with chemotherapy, consists of two phases: the dose escalation phase (Ib) and the dose expansion phase (II).
1. The dose escalation phase (Phase Ⅰb) The primary purpose is to determine the Maximum Tolerated Dose(MTD) and/or dose limiting toxicity (DLT) of HB0025 combined with chemotherapy. The dose escalation is carried out using the "3+3 dose escalation" principle. In the initial stage of the dose escalation process, the chemotherapy dose remains unchanged to explore the safety and tolerability of the currently confirmed safe doses of HB0025 as monotherapy at 10mg/kg, and 20mg/kg, combined with chemotherapy(Pemetrexed 500 mg/m² iv d1+Carboplatin AUC 5 iv d1) in the treatment of advanced non-squamous non-samll cell lung cancer(Non-sq-NSCLC), and combined with chemotherapy( Paclitaxel 175 mg/m² iv d1+ Carboplatin AUC 5 iv d1 ) in advance Endometrial carcinoma(EC).
After completing the first cycle of treatment (DLT evaluation period), if the investigator determines that the subject may benefit from the combined treatment, the subject will continue the treatment cycles (2nd to 4th/5th/6th cycle of HB0025 combined with chemotherapy); if there is no disease progression and no intolerable toxicity, the subject can continue to receive the maintenance treatment with HB0025 + pemetrexed (for non-sq NSCLC) or HB0025 alone (for EC, sq NSCLC), until when intolerable toxicity occurs, disease progression, the subject is lost to follow-up or died, the subject withdraws informed consent, the subject receives other anti-tumor treatment or the study is terminated early, whichever occurs first.
2. Dose expansion phase (Phase II) Based on 1-2 recommended Phase II doses selected by the sponsor and the investigator during the dose escalation process, a multicenter, single-arm study will be conducted to evaluate the efficacy and safety of different doses of HB0025 combined with chemotherapy. Each dosing regimen cohort will be expanded by 40 subjects. If a dosing regimen is not safe or effective, the enrollment of the dosing regimen cohort may be stopped, and the subject quota may be allocated to other dosing regimen cohorts (which may exceed 40 subjects). The dose expansion phase initially plans to expand the following cohorts to further observe the safety of HB0025 combined with chemotherapy and the preliminary efficacy of HB0025 combined with chemotherapy in advanced NSCLC and EC.
After receiving 4-6 cycles of HB0025 combined with chemotherapy, the subjects will enter HB0025 + pemetrexed (for non-sq-NSCLC) or HB0025 alone (for EC, sq-NSCLC) maintenance treatment until when intolerable toxicity, disease progression or death occurs, withdraw informed consent, or receives other anti-tumor treatment or study ends early, early, whichever occurs first.

主要目的：考察HB0025注射液在晚期子宫内膜癌患者中的抗肿瘤疗效。次要目的：考察HB0025注射液在晚期子宫内膜癌患者中的安全性；考察HB0025注射液在晚期子宫内膜癌患者的药代动力学（PK）特征； 考察HB0025注射液的免疫原性。探索性目的：探讨HB0025的药物暴露量-效应关系；探索给药后外周血淋巴细胞的变化，包括CD4 + T细胞和CD8 + T细胞；根据选定的外周血生物标志物，探索HB0025的药效学（PD）效应；探讨HB0025抗肿瘤疗效与生物标志物（包括外周血及肿瘤）的关系。