On March 22, 2024 Alphamab Oncology (stock code: 9966.HK) reported that the phase II clinical research results of anti- PD-L1/CTLA-4 bispecific antibody KN046 plus chemotherapy as first-line treatment for metastatic non-small cell lung cancer (NSCLC) were published online in the renowned journal Cell Reports Medicine (IF: 14.3). Professor Li Zhang from Sun Yat-Sen University Cancer Center is the corresponding author of this paper, and Professor Yuanyuan Zhao is the first author.
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Lung cancer is one of the most common cancers in the world, and it is the malignant tumor with the highest morbidity and mortality in China. According to the latest national cancer statistics released by the National Cancer Center, there are 1.06 million new cases of lung cancer, with a total death toll of 0.73 million in year 2022, far exceeding other tumor types. NSCLC accounts for about 80% – 90% of all lung cancers, and about 57% of NSCLC patients are metastatic at the time of diagnosis. In recent years, immune checkpoint inhibitors have made breakthroughs in the treatment of advanced NSCLC. However, the overall prognosis and long-term therapeutic efficacy still need to be improved.
KN046-202 is a phase II, open-label, multi-center clinical study to evaluate the efficacy, safety and tolerability of KN046 combined with chemotherapy as first-line treatment for metastatic NSCLC. Patients were recruited into two cohorts: patients with non-squamous (non-sq)-NSCLC receive pemetrexed, while those with sq-NSCLC receive paclitaxel, both plus KN046 and carboplatin. Following four cycles (Q3W), maintenance therapy includes KN046 with pemetrexed for non-sq-NSCLC and KN046 for sq-NSCLC. Primary endpoints were confirmed objective response rate (ORR) and duration of response (DoR) as assessed by the investigators according to RECIST version 1.1.
In total, 87 patients were enrolled, including 51 in the non-sq-NSCLC cohort and 36 in the sq-NSCLC cohort. The median age was 61 (range, 32-76) years, and 75.9% were males. As of March 15, 2022, the median follow-up time was 23.1 months.
Efficacy: The confirmed objective response rate (ORR) was 46.0%(95% CI:35.2%-57.0%) and median duration of response (DoR) was 8.1(95% CI:4.14-13.90) months. Median progression-free survival (PFS) was 5.8 (95% CI: 5.26-7.10) months, median overall survival (OS) was 26.6 (95%CI:16.92-NR) months, and the 12-month OS rate was 74.2%(95% CI:63.46%-82.18%). In the non-sq-NSCLC cohort, the confirmed ORR was 43.1%, median DoR was 9.7months, median PFS was 5.8 months, and median OS was 27.2 months; In the sq-NSCLC cohort, the confirmed ORR was 50.0%, median DoR was 7.3months, median PFS was 5.7 months, and median OS was 26.6 months.
Safety: All 87 enrolled patients were evaluable for safety. The most common treatment-related adverse events (TRAEs) were anemia (87.4%), loss of appetite (72.4%), and neutropenia (70.1%). In this study, immune-related adverse event (irAEs), grade ≥3 irAEs, and serious irAEs were reported in 50 (57.5%), 11 (12.6%), and 9(10.3%) patients, respectively. The most common irAEs were pruritus (28.7%), elevated aspartate aminotransferase (24.1%), and rash (21.8%).
In conclusion, the encouraging results from this phase II study showed that KN046 combined with platinum doublet chemotherapy is effective and tolerable as first-line treatment for metastatic NSCLC, which could also be a promising treatment option for this patient population.
About KN046
KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Alphamab. Its innovative designs include: a novel mechanism – CTLA-4 fused with PD-L1 single domain antibody; engineered to target the tumor microenvironment with high PD-L1 expression, and Treg (suppress tumor immunity) clearing function.
There are about 20 clinical trials of KN046 in different stages covering more than 10 types of tumors including NSCLC, pancreatic cancer, thymic cancer, HCC, ESCC and TNBC in Australia, the US and China. The results of these clinical trials have shown an advantage in survival for patients. Alphamab Oncology has received FDA clearance to enter phase II trial of KN046 based on the clinical results in China and Australia. Moreover, KN046 has obtained the U.S. FDA’s orphan drug designation for thymic epithelial tumor in September 2020. Several pivotal clinical trials are currently being conducted, among which the interim analysis of the phase III clinical study of KN046 combined with chemotherapy as the first-line treatment of NSCLC successfully met the prespecified PFS endpoint.
(Press release, Alphamab, MAR 22, 2024, View Source [SID1234657015])