Alphamab Oncology Has Received Approval for JSKN033 Clinical Trial

On Dec 26th, Alphamab Oncology received approval from China’s Center for Drug Evaluation for a Phase I/II clinical trial of JSKN033.

The study demonstrated promising efficacy and safety signals, with results indicating that this combination could enhance antitumor responses in previously untreated patients.

Alphamab Oncology presented clinical data from a Phase II study on the PD-L1/CTLA-4 bispecific antibody KN046 combined with axitinib as a first-line treatment for advanced non-small cell lung cancer (NSCLC) at ESMO 2024.

Title: The efficacy and safety of KN046 combined with Axitinib for previously untreated and checkpoint inhibitor treated advanced non-small cell lung cancer: a single-arm, open-label, multicenter phase II clinical trial

Presentation Type: Poster Presentation

Presentation Number: 133P

Lecture Time: Thursday, 12 December 2024

Speaker: Li Zhang, Sun Yat-Sen University Cancer Center

About KN046

KN046 is a bispecific antibody developed by Alphamab Oncology that targets PD-L1 and CTLA-4 through an innovative mechanism designed to enhance antitumor immunity by targeting tumor microenvironments rich in PD-L1.

The KN046-209 Phase II clinical trial assesses the combination of KN046 and axitinib for advanced non-small cell lung cancer (NSCLC). Preliminary findings presented at ESMO Congress 2023 indicated improved tolerability, safety, and efficacy of this combination as a first-line treatment, with results reported for both previously untreated patients and those who progressed on checkpoint inhibitors.

Methods

The KN046-209 study is a multi-center, open-label Phase II clinical trial assessing the efficacy, safety, and tolerability of KN046, a bispecific antibody targeting PD-L1 and CTLA-4, in combination with axitinib for advanced non-small cell lung cancer (NSCLC) patients without driver mutations.

Participants received KN046 at 5 mg/kg intravenously every three weeks, along with axitinib at either 5 mg or 3 mg orally twice daily.

The primary endpoint is the objective response rate (ORR), while secondary endpoints include safety assessments, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

Results

As of September 1, 2024, the trial included 53 patients in Cohort A (previously untreated with PD-L1 TPS ≥1%) and 32 patients in Cohort B (those who progressed on prior checkpoint inhibitors). The median follow-up times were 14.6 months for Cohort A and 11.2 months for Cohort B.

Among participants, 95.3% had an ECOG performance status of 1, and 85.9% had stage IV disease. In Cohort A, the ORR was 56.8% for PD-L1 TPS ≥1% and 73.3% for TPS ≥50%. The confirmed ORR was slightly lower at 54.5% for TPS ≥1% and 66.7% for TPS ≥50%.

The median duration of response was recorded at 13.2 months for TPS ≥1%, while the median progression-free survival was noted as 8.3 months.

In Cohort B, both the ORR and confirmed ORR were lower at 9.4%, with a DCR of 81.3%.Grade ≥3 treatment-related adverse events occurred in 58.8% of patients, with increased ALT and AST levels being the most common issues. Notably, reducing axitinib to 3 mg significantly decreased severe adverse events without compromising efficacy.

The combination of KN046 and axitinib showed encouraging efficacy and tolerability in advanced NSCLC patients, warranting further validation in larger trials.

The lower dose of axitinib demonstrated comparable efficacy to the higher dose but with improved safety profiles. Higher PD-L1 expression correlated with better responses and longer durations of effect.

About Alphamab Oncology
 

Alphamab Oncology is a biopharmaceutical company focused on developing innovative biotherapeutics for cancer treatment. The company was listed on the Hong Kong Stock Exchange on December 12, 2019 (stock code: 9966). Alphamab’s integrated platform supports research, development, and manufacturing capabilities for biologics, with a strong intellectual property portfolio.

The company specializes in antibody-drug conjugates (ADCs), single-domain antibodies, and bispecific antibodies. Notably, Envafolimab became the first subcutaneously injectable PD-L1 inhibitor approved by Chinese authorities in 2021.

Located in Suzhou Industrial Park, the R&D and industrialization base covers an area of 75 acres and a total design scale of over 40,000 liters, was built in accordance with the NMPA, FDA and EMA GMP standards, ensuring the production of safe and effective cancer treatments at controlled costs for patients