Data from KN046 in Patients with metastatic NSCLC who failed first line treatment or prior EGFR-TKIs Presented at ESMO 2022

• 64 patients with metastatic NSCLC who had failed first-line treatment were enrolled, the median follow-up was 21.6 months and the median OS was 18.40 months, among 41 patients with non-squamous NSCLC, the median OS was 19.81 months, while among 20 patients with squamous NSCLC, the median OS was 12.88 months.
• 26 patients with metastatic NSCLC who failed to EGFR-TKI treatment were enrolled, the median follow-up was 11.56 months. The DCR was 80.8%, and the median OS was 12.68 months.

SUZHOU, China, Sept. 14, 2022 /PRNewswire/ — Alphamab Oncology (stock code: 9966.HK) announced that data from the phase II study of KN046 in patients with metastatic non-small cell lung cancer (NSCLC) who failed first line treatment or prior EGFR-TKIs were presented as a Poster at the ESMO Congress 2022 (ESMO 2022).

KN046-201 is a multicenter, multicohort, open-label, single-arm phase II study to evaluate the efficacy, safety and tolerability of KN046 in patients with NSCLC.

In Cohort A and B, subjects with NSCLC who failed in the first-line platinum-based doublet chemotherapy without PD-(L)1 immune checkpoint blockade therapy were enrolled. Subjects with EGFR mutation and/or ALK translocation were excluded. All subjects enrolled received KN046 3 mg/kg (Cohort A) or 5 mg/kg (Cohort B) Q2W intravenous administration, respectively. The primary endpoint was ORR according to RECIST v1.1 by IRC.

In Cohort D, subjects with EGFR sensitivity mutation (Ex19del or L858R), who failed to prior EFGR-TKIs treatment 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), until disease progression, intolerable toxicity or other discontinuation criteria. Primary endpoint was objective response rate (ORR) per RECIST version 1.1.

Title: A phase II study of KN046 (an anti-PD-L1/CTLA-4 bispecific antibody) in patients with metastatic non-small cell lung cancer (NSCLC) who failed in the first-line treatment

Poster Number: 1022P

First author: Caicun Zhou, Prof, Shanghai Pulmonary Hospital

As of April 30, 2020, 64 patients with metastatic NSCLC who had failed first-line treatment were enrolled. As of the date of data cut-off, August 31, 2021, the median follow-up was 21.6 months (95% CI: 20.3 to 23.2).

Among 64 patients, the ORR was 14.1% (9/64, 95% CI: 6.64 to 25.02), the median PFS was 3.68 months (95% CI: 2.89 to 5.52) and the median OS was 18.40 months (95% CI: 12.88 to 21.91). Among 41 patients with non-squamous NSCLC, the ORR was 17.1% ( 95% CI: 7.15 to 32.06), the median PFS was 3.68 months (95% CI: 2.76 to 5.45) and the median OS was 19.81 months (95% CI: 13.04 to 23.36), while among 20 patients with squamous NSCLC, the ORR was 10.0% (95% CI: 1.23 to 31.70), the median PFS was 7.43 months (95% CI: 1.81 to 14.39) and the median OS was 12.88 months (95% CI: [above 8.97]).

In terms of the treatment-related adverse event (TRAE), 27(42.2%) out of the 64 subjects had experienced TRAE at grade 3 or higher levels. The most common (≥10%) TRAEs were anemia (18/64 [28.1%]), hyperglycemia (17/64 [26.6%]), infusion-related reaction (17/64 [26.6%]), rash (13/64 [20.3%]), etc.

KN046 was well tolerated and effective as second line treatment of advanced NSCLC. KN046 showed promising OS benefit in both squamous and non-squamous NSCLC.

Title: A phase II study of KN046 (an anti-PD-L1/CTLA-4 bispecific antibody) in patients with metastatic non-small cell lung cancer (NSCLC) who failed to prior EGFR-TKIs treatment

Poster Number: 1034P

First author: Caicun Zhou, Prof, Shanghai Pulmonary Hospital

As of December 17, 2021, 26 patients with metastatic NSCLC were enrolled. As of the date of data cut-off, January 25, 2022, the median follow-up was 11.56 months (95% CI: 7.66 to 12.52).

Among 26 patients, the ORR was 26.9% (95% CI: 11.57 to 47.79), the DCR was 80.8% (95% CI: 60.65 to 93.45) with 7 PR and 14 SD, and the CBR(CR+PR+SD≥12 weeks) was 65.4% (95 CI%: 44.3 to 82.79). The median PFS was 5.52 months (95% CI: 4.17 to 6.77) and the median OS was 12.68 months (95% CI: [above 11.4]). The 12-month OS rate was 71.57% (95% CI, 43.59 to 87.39).

In terms of the treatment-related adverse event (TRAE), 14(53.8%) out of the 26 subjects had experienced TRAE at grade 3 or higher levels. 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 well tolerability and promising efficacy in treatment of advanced NSCLC with EGFR sensitivity mutation who failed to prior EGFR-TKIs treatment.

Professor Zhou Caicun from Shanghai Pulmonary Hospital, the principal investigator, commented: "Lung cancer is a malignant tumor with extremely high morbidity and mortality, among which non-small cell lung cancer accounts for about 80% of lung cancer. Immunotherapy combined with chemotherapy has become the standard first-line regimen for this patient population. We are pleased to see that, not only in squamous and non-squamous NSCLC, but also in EGFR-mutant advanced NSCLC patients failed to prior EGFR-TKIs treatment, the anti-PD-L1/CTLA-4 bispecific antibody (KN046) independently developed by Alphamab Oncology, showed good tolerability, efficacy and promising OS benefits. At present, the phase III clinical study of KN046 combined with chemotherapy in the treatment of non-small cell lung cancer has reached its primary endpoint of PFS assessed by independent review. We believe that the further survival benefit will observed in long-term follow-up, and hope this new therapy will benefit more patients."

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. 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.

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