- 2-year survival data of this study were presented: KN046 combined with platinum doublet chemotherapy showed promising efficacy and well tolerated safety as first-line（1L）treatment for advanced NSCLC patients
- In 87 efficacy evaluable patients, confirmed ORR was 46%.
- Median OS in non-squamous NSCLC and squamous NSCLC were 27.2 months and 26.6 months respectively.
- The phase III clinical study of KN046 combined with chemotherapy treatment for sq -NSCLC has met the prespecified PFS endpoint in the first interim analysis, OS follow-up is ongoing.
SUZHOU, China, Sept. 14, 2022 /PRNewswire/ -- Alphamab Oncology (stock code: 9966.HK) announced that the updated data from Phase 2 Clinical trial on KN046 Combined with platinum doublet chemotherapy as first-line（1L）treatment for NSCLC were poster presented at 2022 ESMO annual conference.
Topic: Two-year follow-up from KN046 in combination with Platinum doublet chemotherapy as first-line（1L） treatment for NSCLC: an open-label, multi-center phase 2 trial
Poster number: 1029P
First author: Professor Li Zhang, Sun Yat-sen University Cancer Center
KN046-202 (NCT04054531) is a phase II, open-label, multi-center clinical study to evaluate the efficacy, safety and tolerability of KN046 combined with platinum doublet chemotherapy in patients with advanced non-small cell lung cancer. Patients were recruited into two cohorts based on histological type (non-sq NSCLC into cohort 1 and sq-NSCLC into cohort 2). Patients with non-sq NSCLC received KN046 (5 mg/kg), carboplatin (AUC=5), and pemetrexed (500 mg/m2). The sq-NSCLC group received KN046 (5 mg/kg), carboplatin (AUC=5), and paclitaxel (175 mg/m2). Chemotherapy was given for 4 cycles, while KN046 was administered once every 3 weeks (Q3W) and Pemetrexed could also be continued in the non-sq NSCLC cohort. Primary endpoints were confirmed objective response rate (ORR) and duration of response (DOR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS), etc.
Previously, the results of this study showed that KN046 combined with platinum doublet chemotherapy is well tolerated and has shown promising clinical benefit as 1L treatment for stage IV NSCLC. The confirmed objective response rate and progression-free survival (PFS) data were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. The 2022 ESMO annual meeting presents the results of the 2-year follow-up. The updated data further showed that KN046 combined with platinum doublet chemotherapy is a clinically promising treatment strategy as first-line treatment of NSCLC. The median overall survival (OS) over 2 years in both cohorts are very encouraging.
As of March 15, 2022, the median follow-up was 23.1 months (Interquartile Range [IQR] 20.7,26.9). 87 patients with advanced NSCLC who have not received systemic treatment were enrolled, including 51 patients with non-squamous NSCLC (cohort 1) and 36 patients with squamous NSCLC (cohort 2). The median age was 61 years, and 82.8% of patients ECOG PS was 1 and 17.2% of patients was 0.
In 87 efficacy evaluable patients, confirmed ORR was 46% (95% CI: 35.2, 57.0). DoR of cohort 1 and cohort 2 were 9.7 months (95% CI:4.01, 20.73) and 7.3 months (95% CI:3.52, -).
Among all enrolled patients, the median PFS in cohort 1 and cohort 2 were 5.8 months (95% CI: 4.80, 7.16) and 5.7 months (95% CI: 4.17, 8.71), and median OS were 27.2 months (95% CI: 15.18, -) and 26.6 months (95% CI: 12.19, -) respectively.
In terms of safety, the most common KN046 related TEAEs (≥Grade3) were Diarrhea (6.9%, 6/87), Alanine aminotransferase increase (4.6%, 4/87) and Rash (4.6%, 4/87), etc. The incidence of ≥Grade 3 Immune-related AEs was 12.6%( 11/87),and the adverse events were manageable.
"In recent years, immunotherapy has become the standard treatment for advanced NSCLC, but there are still needs for innovative medicine and therapeuticsto improve the overall survival." said the principal investigator of the study, Professor Zhang Li from Sun Yat-sen University Cancer Hospital. "We are pleased to share the latest progress of the KN046-202 study at 2022 ESMO annual meeting. The 2-year follow-up results confirmed that both non-squamous and squamous NSCLC can benefit from KN046 as first-line treatment in the long-term, which brings great encouragement for patients and physicians. I believe it will benefit for more patients."
KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu 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. Four 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.
About Alphamab Oncology
Alphamab Oncology is focusing on innovation, including discovery, development, production and commercialization of anti-tumor drugs. On December 12, 2019, the Company was listed in the mainboard of Hong Kong Stock Exchange with stock code 9966.
Alphamab has a fully integrated proprietary biologics platforms in bi-specifics and protein engineering. Its highly differentiated in-house pipeline consists of tumor monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates. Six products have advanced into phase I-III clinical trials in China, the United States, Japan and Australia and in November 2021, one of these products, the unique PD-L1 antibody for subcutaneous administration, Envafolimab, received marketing authorization from the Chinese National Medical Products Administration (NMPA) for the treatment of previously treated MSI-H/dMMR advanced solid tumors.
The Company also has state-of-the-art manufacturing capabilities designed and built to meet NMPA and EU/FDA's cGMP standards and a complete quality system which has passed the on-site inspection of a European Union qualified person. Alphamab Oncology is committed to building a global leading, multi-dimensional drug development and commercialization platform, focusing on multifunctional biological innovative drugs, and to benefit patients in China and around the world.