Suzhou, June 6, 2022 - Alphamab Oncology (stock code: 9966.HK) announced that research updates from four clinical studies of KN046 (PD-L1/CTLA-4 bispecific antibody) presented as a poster or published online at the 2022 American Society of Clinical Oncology Annual Meeting (2022 ASCO).
01
Title: A Multicenter, Randomized, Double-Blind Phase III Clinical Study to Evaluate the Efficacy and Safety of KN046 Combined with Nab-Paclitaxel and Gemcitabine Versus Placebo Combined with Nab-Paclitaxel and Gemcitabine in Patients with Advanced Pancreatic Cancer (ENREACH-PDAC-01)
Abstract Number: TPS4189
Poster Number: 159b
Most patients with pancreatic cancer, one of the most aggressive malignancies, are diagnosed as locally advanced (unresectable) or metastatic disease. The resistance of nab-paclitaxel and gemcitabine (AG regimen) is unavoidable as a common treatment regimen for advanced pancreatic cancer. The efficacy of immunotherapy combined with chemotherapy was identified in some types of cancers, however it was not achieved in pancreatic cancer. KN046, a novel recombinant humanized bispecific antibody, can simultaneously block PD-1/PD-L1 pathways and CTLA-4 pathways, and restore T cell immune responses.
In a phase II clinical study (KN046-IST-04), KN046 combined with AG regimen showed preliminary promising efficacy in patients with unresectable locally advanced or metastatic pancreatic cancer, which was presented at the 2021 ASCO Annual Meeting as a poster, then updated at the 2021 CSCO Annual Meeting. As of May 26, 2021, 22 patients had at least one tumor assessment with 50% ORR and 95.5% DCR. The 6-month progression-free survival rate (PFS-6M Rate) was 62.3%; Even there were 4 patients received tumor resection after they achieved partial remission (PR) and assessed by the MDT team for the surgery possibility. The Pivotal Phase III study (ENREACH-PDAC-01) was initiated in China to evaluate the efficacy and safety of KN046 in combination with nab-paclitaxel and gemcitabine as first-line treatment for advanced pancreatic cancer (NCT05149326) based on the efficacy and safety of KN046-IST-04.
ENREACH-PDAC-01 is a Phase III randomized, double blind, placebo-controlled， multicenter study to evaluate the efficacy and safety of KN046 in combination with nab-paclitaxel and gemcitabine as first-line treatment for advanced pancreatic cancer. This study planned to enroll 408 patients with histologically or cytologically confirmed unresectable locally advanced or metastatic PDAC (ECOG performance status of 0 or 1 and expected survival period of more than 3 months). Enrolled patients were randomized 1:1 to receive 4-6 cycles of KN046 or placebo plus nab-paclitaxel and gemcitabine, followed by KN046 or placebo plus gemcitabine as maintenance treatment. Tumor assessments will be evaluated every 8 weeks per RECIST 1.1. The primary endpoint is OS, and the key secondary endpoints were ORR and PFS. The first patient was dosed in Feb 2022.
Professor Gang Jin from Shanghai Changhai Hospital, the leading PI of the study, commented: "We are delighted to share the latest research progress on KN046 for advanced pancreatic cancer at ASCO. The AG regimen is the first-line standard of care for advanced pancreatic cancer worldwide, but with limited efficacy and chemoresistance is unavoidable. KN046 combined with AG regimen achieved better ORR in a phase II study, which is expected to bring new breakthroughs in the treatment of advanced pancreatic cancer. We look forward to the advancement of this phase III study with the aim of bringing better treatment options for patients with advanced pancreatic cancer."
Professor Jianming Xu from the First Medical Center of PLA General Hospital, the co-leading PI, commented: "We are pleased to see that this new therapy, KN046 combined with AG regimen, received attention at 2022 ASCO. Based on the data from previous studies, we believe that for patients with advanced pancreatic cancer, KN046 combined with AG regimen will be a potentially better therapy and can extend survival for patients. We look forward to the positive results of this phase III study, so that more patients can benefit from this innovative therapy as soon as possible."
02
Title：A phase II study of KN046 monotherapy as 2nd line and above treatment for unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC)
Abstract Number: e16305
This clinical trial in China is to evaluate the efficacy and safety of KN046 monotherapy as 2nd line and above treatment for unresectable locally advanced or metastatic PDAC. This trial enrolled unresectable locally advanced or metastatic PDAC patients with ECOG PS of 0-1 and prior at least one systemic anti-tumor treatment. KN046(5mpk, Q2W) monotherapy were administered until disease progression or intolerable toxicity. Tumor response was assessed every 8 weeks according to RECIST 1.1 by investigator. The primary endpoint is investigator-assessed objective response rate (ORR). Secondary endpoints included disease control rate (DCR), PFS, OS and safety, etc.
As of Jan 10, 2022, 21pts were enrolled with median (range) age 57 (51-64).Out of 21 pts, 14 (66.7%) had ECOG 1, 16 (76.2%) pts had distant metastases, and 11 (52.4%) pts had received ≥2 lines systemic treatment.All pts received KN046 treatment were evaluable for safety with 4.1(2.1,6.4) wks median exposure time, 9 pts were assessed for efficacy with 1 PR and 2 SD. Confirmed ORR was 11.1% (95% CI: 0.28-48.25), and DCR was 44.4% (95% CI: 13.7-78.8). Median PFS was 2.1 months (95% CI:1.61-7.29) with 31.4% PFS-6m rate and 21.0% PFS-9m rate, respectively. Median OS was 7.5 months (95% CI:3.02-NR) with 61.3% OS-6m rate and 49.5% OS-9m rate, respectively. The incidence of KN046 related treatment-emergent adverse events (TRAE) was 71.4% (15/21), with 14.3% (3/21) ≥grade 3 TRAEs. Two pts experienced TRAE leading to discontinuation. The most common TRAEs (≥10%) were rash (n=6, 28.6%), alanine aminotransferase increased, chills, γ-glutamyl transferase increased and platelet count decreased (n = 3, 14.3%, respectively). No TRAE leading to death occurred.
03
Title：A phase II study combining KN046 (an anti-PD-L1/CTLA-4 bispecific antibody) and lenvatinib in the treatment of advanced unresectable or metastatic hepatocellular carcinoma (HCC): Updated efficacy and safety results
Abstract Number: 4115
KN046-IST-05 is an open-label, single-arm, multicenter, phase II trial to enroll unresectable or metastatic HCC pts with Barcelona Clinic Liver Cancer (BCLC) stage B or C who were not suitable for curative surgery or local therapy. Patients received lenvatinib 12 mg/day (bodyweight [BW] ≥60 kg) or 8 mg/day (BW<60 kg) orally and KN046 (5mg/kg Q3W IV) on Day 1 of a 21-day cycle until disease progression or intolerable toxicity or 2-year treatment. Primary endpoints were safety and ORR assessed by investigators per RECIST v1.1.
As of January 7, 2022, 55 enrolled pts received KN046 combined with lenvatinib treatment with 25 weeks median treatment duration. For 52 evaluable pts, ORR was 51.9% (95% CI 37.6-66.0) and DCR was 86.5% (95% CI 74.2-94.4) by RECIST v1.1. Median PFS was 9.3 months (95% CI 7.0–NE), The median OS and DOR were not reached. KN046+lenvatinib showed a promising efficacy in ORR and PFS and manageable safety profile in the first-line advanced unresectable or metastatic HCC treatment. These results might support the KN046 combined lenvatinib treatment as a potential new treatment option for HCC patient.
04
Title：Phase II study of KN046 in patients with thymic carcinoma who failed immune checkpoint inhibitors
Abstract Number: TPS8607
Poster Number: 223b
Thymic carcinomas are the most aggressive form of thymic epithelial tumors. Compared with thymomas ,they are often inoperable and more resistant to chemotherapy. This is a phase II clinical trial to evaluate the efficacy and safety of KN046 in the treatment of patients with advanced thymic carcinoma who progressed after prior treatment with immune checkpoint inhibitor therapy.
Key eligibility criteria include thymic carcinoma with progression after treatment with an immune checkpoint inhibitor with no limit to prior lines of therapy, adequate organ function and performance status. History of prior or current autoimmune disorders are not allowed and history of baseline positive anti-acetylcholine receptor (AChR) autoantibody are not allowed. KN046 will be administered intravenously at 5 mg/kg every 2 weeks until progression or excessive toxicity, or up to 2 years. A cycle is defined as 2 treatments (28 days). The primary objective is to evaluate the antitumor activity of KN046 in patients with thymic carcinoma as measured by overall response rate defined by RECIST 1.1 criteria. The secondary objectives are to assess the safety and tolerability of KN046 including safety as measured by the number of adverse events (CTCAE 5.0), duration of response (RECIST 1.1) from first documented response to the date of first documented disease progression, progression-free survival, and overall survival. Exploratory objectives include the association of biomarkers (PD-L1 expression, tumor immune microenvironment determined by multiplex IHC, tumor mutational burden, T-cell inflamed gene expression profile) and clinical efficacy parameters. We will also characterize the safety laboratory results (AChR autoantibodies and creatinine kinase) and the occurrence of adverse events of interest. Simon’s two-stage design will be used. The null hypothesis that the true response rate is 5% will be tested against a one-sided alternative of target response rate ≥20%. In the first stage, 10 patients will be accrued. If there are no responses in the first stage, then the study will be stopped. Otherwise, 19 additional patients will be accrued for a total of 29 patients. The null hypothesis will be rejected if ≥4 responses are observed in 29 patients, with a type 1 error rate of 0.05 and power of 80%. The study was initiated at Weill Cornell Medicine in December 2021.
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, thymic cancer, pancreatic 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.
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. Five 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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