Alphamab Oncology Announces New Data from Multiple Studies of KN046 with Lung Cancer and Thymic Carcinoma at ESMO

• KN046 showed encouraging efficacy result especially in OS benefit (mOS: 20.2 months) in advanced NSCLC with EGFR sensitivity mutation who progressed after EGFR-TKI(s).
• KN046 showed encouraging efficacy result especially in OS benefit (mOS: 13.3months) in advanced NSCLC with EGFR sensitivity mutation who progressed after EGFR-TKI(s) treatment.
• KN046 combined with axitinib is well tolerated and has shown very promising efficacy as 1L treatment for advanced NSCLC. Safety signals were manageable.
• KN046 demonstrated promising antitumor activity and acceptable toxicity in thymic carcinoma patients who have failed after ≥ 1L therapy. By the cut-off date, the mOS is not mature and 24-months OS rate was 72.1%, which was numerically higher than literature reported.

SUZHOU, China, Oct. 24, 2023 /PRNewswire/ -- Alphamab Oncology (stock code: 9966.HK) announced the results of four studies of PD-L1/CTLA-4 bispecific antibody KN046 at the European Society of Medical Oncology (ESMO) Annual Meeting, held October 20-24 in Madrid, Spain.

Title: Updated results of the efficacy and safety of KN046 (a bispecific anti-PD-L1/CTLA-4) in patients with metastatic non-small cell lung cancer (NSCLC) who failed prior EGFR-TKI(s)
Poster ID: 1330P
Corresponding Author: Prof. Caicun. Zhou, Shanghai Pulmonary Hospital
First author: Dr. Anwen. Xiong, Shanghai Pulmonary Hospital

KN046-201 is an open-label, multi-center, multi-cohort and single-arm phase II clinical trial designed to evaluate the efficacy, safety and tolerability of KN046 for the treatment of NSCLC. We previously showed the efficacy and safety of KN046 plus chemotherapy in advanced NSCLC with EGFR sensitivity mutation who progressed after tyrosine kinase inhibitor(s) (TKIs) from Cohort D. Here, we report the updated survival and safety data. In Cohort D, subjects with EGFR sensitivity mutation (Ex19del or L858R), who had failed from prior EFGR-TKIs without platinum-based chemotherapy were enrolled. All subjects enrolled received KN046 5mg/kg Q3W combined with chemotherapy (Pemetrexed, 500 mg/m2, Q3W and carboplatin AUC5, Q3W). From Jan 7, 2020 to Dec 17, 2021, 26 patients with metastatic NSCLC were enrolled. The median follow-up was 17.8 months (95% CI, 13.0, 19.5) at the data cutoff of Jul 30, 2022.

Among all 26 patients, the ORR was 26.9% (7/26, 95% CI, 11.6，47.8) and 5 pts had tumor shrink rate ≥50%. DCR was 84.6% (22/26, 95% CI, 65.1, 95.6%) with 7 PR and 15 SD. The CBR was 38.5% (10/26, 95% CI, 20.2, 59.4). Median progression-free survival (mPFS) was 5.5 months (95% CI, 4.2, 6.8) and median overall survival (mOS) was 20.2 months (95% CI, 11.5, -). The 12-month OS rate was 65.29% (95% CI, 42.16, 81.02).

In terms of the treatment-related adverse event (TRAE), 15 (57.7%) out of the 26 subjects had experienced TRAE at grade 3 or higher levels due to chemotherapy or KN046. The most common (≥10%) TRAEs were anemia (11/26 [42.3%]), AST increased (11/26 [42.3%]), ALT increased (9/26 [34.6%]), infusion-related reaction (8/26 [30.8%]), etc.

KN046 showed encouraging efficacy result especially in OS benefit and a favorable safety profile in advanced NSCLC with EGFR sensitivity mutation who progressed after EGFR-TKI(s). Further study is warranted to confirm the clinical results.

Title:  Efficacy and safety of KN046 (a bispecific anti-PD-L1/CTLA-4) in patients with metastatic non-small cell lung cancer who previously treated with immune checkpoint inhibitor(s)
Poster ID: 1459P
Corresponding Author：Prof. Caicun. Zhou, Shanghai Pulmonary Hospital
First author: Dr. Anwen. Xiong, Shanghai Pulmonary Hospital

KN046-CHN-001 and KN046-201 assessed the efficacy, safety and tolerability of KN046 in NSCLC. We present the efficacy and safety outcomes of KN046 in this population from KN046-CHN-001 and Cohort C of KN046-201. Eligible patients had NSCLC that progressed after ICI(s) and platinum-based chemotherapy. Patients with EGFR mutation and/or ALK translocation were excluded. All patients received KN046 (26 at 5 mg/kg Q2W, 2 at 5 mg/kg Q3W, 2 at 300mg Q3W and 1 at 3 mg/kg Q2W) by IV infusion. Between April 19, 2019 and July 13, 2020, 31 pts with metastatic NSCLC who failed ICI(s) and platinum-based chemotherapy were enrolled. At the data cutoff of July 30, 2022 for KN046-201 and August 31, 2021 for KN046-CHN-001, the median follow-up was 25.0months (95% CI, 24.4, NE).

Among all 31 pts, the ORR was 3.2% (1/31, 95% CI, 0.1, 16.7), disease control rate (DCR) was 38.7% (12/31, 95% CI, 21.8, 57.8), clinical benefit rate (CBR) was16.1% (5/31, 95% CI, 5.5, 33.7%). Median progression-free survival (mPFS) was 2.8 months (95% CI, 1.8, 3.7) and median overall survival (mOS) was 13.3 months (95% CI, 6.5, 17.5). The 12-month OS rate was 54.8% (95% CI, 35.97, 70.26).

In terms of the treatment-related adverse event (TRAE), 7(22.6%) out of the 31 subjects had experienced treatment-related adverse event (TRAE) at grade 3 or higher levels. Commonly reported TRAEs of grade 3 or higher were anemia (9.7%), febrile neutropenia (3.2%), fatigue (3.2%) etc.

KN046 was well tolerated and demonstrated encouraging OS benefit in NSCLC patients who had failed prior ICI(s) therapy. Further study is warranted to confirm the clinical results.

Title: The preliminary data from a single-arm, open-label, multicenter phase 2 clinical trial: KN046 combined with axitinib as first-line (1L) treatment for NSCLC
Poster ID: 1449P
Corresponding Author: Prof. Li Zhang, Sun Yat-Sen University Cancer Center
First author: Prof. Yuanyuan Zhao, Sun Yat-Sen University Cancer Center

KN046 combined with platinum doublet chemotherapy as 1L treatment for metastatic NSCLC had shown promising efficacy and tolerability in the previous clinical trial. KN046-209 is an ongoing, multicenter, open-label, phase II study enrolled treatment-naive patients with PD-L1-positive (TPS≥1%) locally advanced or metastatic non-small-cell lung cancer (NSCLC). To evaluate the efficacy and safety of KN046 combined with axitinib. The primary endpoint was objective response rate (ORR). Herein, we present the promising preliminary data of KN046 combination with axitinib as 1L treatment for NSCLC.

38 subjects were enrolled. 86.8% were male. 86.8 % (33/38) were stage IVa or IVb. The proportion of subjects with PD-L1 expression ≥50% was lower(26.3%) than previously reported(about 40%).

In the efficacy analysis set, The ORR was 58.6% (17/29, 95% CI: 38.936, 76.476). Subjects with higher PD-L1 expression had a higher objective response rate. The median PFS follow-up was 4.172 months (1.413, 6.867). The mPFS was 8.345 months (95% CI: 5.454, NE), which is immature. The mOS was not reached.

The incidence of KN046-related TRAE was 78.9% (30/38). The incidence of irAE was 15.8% (6/38). Only 2 subjects had Grade ≥3 irAE. There was no KN046-related death. The incidence of KN046-related CTCAE Grade ≥3 TRAE was 23.7% (9/38). The most frequent TRAE was AST increased 7.9% (3/38), ALT increased 5.3% (2/38), diarrhoea 5.3% (2/38).

KN046 combined with axitinib is well tolerated and has shown very promising efficacy and safety signal in 1L treatment for advanced NSCLC. The 2^nd stage of enrollment is ongoing and a phase III RCT for the 1^st line NSCLC patient is planned to confirm the combination of KN046 and axitinb as a viable chemo free option.

Title: KN046 in Patients with ≥2L R/M Thymic Carcinoma: A Prospective, Single-arm, Multi-center, Phase 2 Study
Poster ID: 1449P
Corresponding Author: Prof. Xiaolong Fu, Shanghai Chest Hospital
First author: Prof. Wentao Fang, Shanghai Chest Hospital

KN046-205 was a prospective, muti-center, single-arm phase 2 clinical study, in order to evaluate the efficacy and safety of KN046 in patients with ≥ 2l R/M thymic carcinoma. All the subjects would receive intravenously 5mg/kg Q2W dose, until tumor progression or unacceptable toxicity occurred. Tumor response was assessed every 8 weeks per RECIST 1.1, Objective response rate (ORR) as assessed by an Independent Review Committee (IRC) was the primary endpoint. By the cut-off date (30 August, 2023), 48 subjects were enrolled. The median follow-up was 21.5 months (IQR: 16.7, 24.8).

45 subjects had tumor assessment after baseline. The objective response was 15.6% (95% CI: 6.5%, 29.5%), and the clinical benefit rate (CBR) was 31.1% (95%CI: 18.2%, 46.7%). The median duration of response (mDoR) was 14.7 months (95%CI: 1.9, NE), and the progression-free survival was 3.9 months (95% CI: 1.3, 11.3). The overall survival was not reached, and the 12-months survival rate and 24-months survival rate was 92.4% (95%CI: 78.3%, 93.5%) and 72.1% (95%CI: 53.8%, 84.4%), respectively. There were 16 subjects with TPS ≥ 1% enrolled in the trial. The ORR and CBR were 18.8% (95% CI: 4.1%, 45.7%), respectively. The mPFS is 5.7 months (95% CI: 1.8, NE), which was numerically higher than subjects with TPS﹤1% or unknown.

The most common treatment-related adverse events (TRAE) of any grade include rash (18/48, 37.5%), AST increased (15/48, 31.3%), ALT increased (13/48,27.1%), and anemia (22.9%).19 subjects experienced ≥ 3 grade TRAE.

KN046 demonstrated promising antitumor activity and acceptable toxicity in thymic carcinoma patients who have failed after ≥ 1L therapy. By the cut-off date, the mOS is not mature and 24-months OS rate was 72.1%, which was numerically higher than literature reported.

About KN046

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. 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.

About Alphamab Oncology

Alphamab Oncology is a biopharmaceutical company dedicated to the discovery, development manufacturing and commercialization of world-class innovative biotherapeutics for cancer treatment. On December 12, 2019, Alphamab Oncology was listed on the Main Board of Hong Kong Stock Exchange, with the stock code:9966.

To make cancer manageable and curable, Alphamab Oncology has always been guided by clinical value and patient needs, and focuses on the development of innovative, safe and affordable anti-tumor drugs to benefit patients in China and around the world.

We have created a biological macromolecule drug discovery, research and development, manufactured technology platform with independent intellectual property rights such as protein/antibody engineering, antibody screening, multi-module/multi-functional antibody modification.

With multiple in-house proprietary technology platforms, Alphamab Oncology has established a globally competitive and differentiated pipeline which consists of tumor single domain antibody/monoclonal antibodies, multi-functional antibodies, and antibody-drug conjugates. Among them, The world's first subcutaneous PD-L1 inhibitor injection (Envafolimab) has been obtained the market approval by the Chinese National Medical Products Administration, several varieties have entered the critical clinical stage in China and the United States, 2 varieties were selected into the national special project of " New Drug Development", and 3 varieties were granted 4 orphan drug qualifications by FDA.

SOURCE Alphamab Oncology