The annual global oncology event – American Society of Clinical Oncology (ASCO) The annual meeting will be held from June 3 to June 7, 2022 local time. In this meeting, a number of exploratory studies on new therapeutic strategies such as cellular immunotherapy and bispecific antibodies were amazing. Among them, KN046, as a bispecific antibody targeting PD-1/PD-L1 and CTLA-4, has attracted much attention. Professor Xing Baocai from Peking University Cancer HospitalThe team reported the results of a phase II study of KN046 in hepatocellular carcinoma (HCC) at the meeting¹. , Prof. Jin Gang from Shanghai Changhai Hospital also announced at the meeting the ongoing phase III study of KN046 for pancreatic cancer Background and methodology of the ENREACH-PDAC-01 trial². Yimaitong organizes the above two studies as follows for readers.
KN046 in combination with lenvatinib in stage II patients with advanced unresectable or metastatic HCC Study: Updated Efficacy and Safety Results
Study Background
Previous studies have shown that PD-1 inhibitors combined with lenvatinib can improve the objective response rate (ORR) of patients with metastatic HCC. For advanced unresectable or metastatic HCC, the researchers evaluated the efficacy and effectiveness of KN046 combined with lenvatinib. safety. The preliminary results of the study suggest that the combination regimen has good efficacy and tolerable safety. updated.
Research Methods
This is an open label , A single-arm, multicenter, phase II clinical trial, the patients included are patients with unresectable or metastatic HCC, the patients are staged in Barcelona Clinic Liver Cancer (BCLC) stage B or C, and are not suitable for radical surgery or local therapy. The enrolled patients received oral lenvatinib 12 mg/day (body weight ≥ 60 kg) or 8 mg/day (body weight < 60 kg), and simultaneously received KN046 5 mg IV, d1 q3w treatment. Treatment continued for two years or disease progression or toxicity was not tolerated. The primary endpoints of the study were safety and ORR as assessed by each investigator according to RECIST v1.1.
Study Results
January 7, 2022 At data cutoff, 55 patients were enrolled in the study, and the median duration of treatment was 25 weeks. Among them, 52 patients were evaluable. According to RECIST v1.1, the ORR was 51.9% (95%CI 37.6%-66.0%), and the disease control rate (DCR) was 86.5% (95%CI 74.2%-94.4%). . The median progression-free survival (PFS) was 9.3 months (95% CI 7.0–NE), and the median overall survival (OS) and duration of response (DOR) were not reached.
The overall incidence of KN046 treatment-related adverse events (TRAEs) was 98.2%, of which the incidence of grade 3 TRAEs was 27.3%. The most common grade ≥3 TRAEs were decreased platelet count (7.3%) and increased aspartate aminotransferase (3.6%). The incidence of immune-related adverse events (irAEs) was 14.5%, and the incidence of grade ≥3 irAEs was 5.5%. Three patients had discontinuation of KN046 treatment due to grade ≥3 TRAEs, namely infusion-related reactions, decreased platelet counts, and interstitial lung disease. Four patients died due to TRAE of KN046, including 1 patient with hyponatremia, 2 patients with interstitial lung disease, and 1 patient with unknown cause of death.
Conclusions
As advanced unresectable or metastatic As the first-line treatment for patients with chronic HCC, KN046 combined with lenvatinib performed better in terms of ORR and PFS, and the safety was controllable. The findings provide evidence support for KN046 in combination with lenvatinib as a potential new treatment option for such patients.
Multicenter, randomized, double-blind phase III clinical study ENREACH-PDAC-01: KN046 in combination Application of nab-paclitaxel and gemcitabine in advanced pancreatic cancer
Research background
Pancreatic cancer is highly aggressive, and most patients are diagnosed with locally advanced or advanced disease. Albumin paclitaxel combined with gemcitabine (AG regimen) is a commonly used treatment regimen for advanced pancreatic cancer, but chemotherapy resistance is an urgent problem to be solved in clinical practice. Immunotherapy combined with chemotherapy may address drug resistance, but this strategy has not been recognized in pancreatic cancer. A previous phase II clinical study (NCT04324307) suggested that for 31 patients with unresectable advanced pancreatic cancer, the ORR of KN046 combined with AG regimen was 45.2% (95%CI 27.3%-64.0%), and the DCR was 93.5% (95%CI) 78.6%-99.2%), the program has a good effect. Based on this, the researchers conducted this China Phase III pivotal study (ENREACH-PDAC-01) to verify the efficacy and safety of KN046 combined with AG regimen in the first-line treatment of advanced pancreatic cancer.
Methods
The study inclusion criteria were organized by Patients with unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma confirmed by histopathology or cytology, with a WHO performance score of 0 or 1, expectedSurvival period is more than 3 months. Patients were randomly assigned to the intervention group or the control group according to 1:1 to receive 4-6 cycles of KN046 (5 mg/kg Q2W) combined with AG regimen or placebo combined with AG regimen, and sequentially KN046 (5 mg/kg) Q2W) plus gemcitabine or placebo plus gemcitabine maintenance therapy. Treatment continued until disease progression, or intolerable toxicity, or patient withdrawal of informed consent, loss to follow-up, or death, or study termination. The primary endpoint of the study was OS, and the key secondary endpoints were ORR and PFS.
The research is still in progress, and the conclusions of the research result set have not been published yet, and Yimaitong will keep paying attention.
References:
1. Baocai Xing, et al. A phase II study combining KN046 (an anti-PD-L1/CTLA-4 bispecific antibody) and lenvatinib in the treatment for advanced unresectable or metastatic hepatocellular carcinoma (HCC): Updated efficacy and safety results. J Clin Oncol 40, 2022 (suppl 16; abstr 4115)
2. Gang Jin, et al. A multicenter, randomized, double-blind phase III clinical study to evaluate the efficacy and safety of KN046 combined with nab-paclitaxel and gemcitabine versus placebo combined with nab-paclitaxel and gemcitabine in patients with advanced pancreatic cancer (ENREACH-PDAC-01). J Clin Oncol 40, 2022 (suppl 16; abstr TPS4189)
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