SUZHOU, China I October 7, 2024 I MediLink Therapeutics (Suzhou) Co., Ltd. (“MediLink”), a clinical-stage biotech company, today announced a global clinical trial collaboration and supply agreement with Amgen Inc. Amgen will lead a global clinical study to evaluate the therapeutic potential of the combination of MediLink’s B7-H3-targeting antibody-drug conjugate (ADC) YL201 and Amgen’s DLL3- and CD3-targeting bispecific T-cell engager (BiTE®) IMDELLTRA™ in extensive-stage small cell lung cancer (ES-SCLC) under the clinical trial collaboration and supply agreement. MediLink will provide the investigational drug YL201 for the combination study.
This open-label, global, multi-center Phase Ib clinical study is designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of this combination regimen in ES-SCLC patients.
Both YL201 and IMDELLTRA™ have shown potential in ES-SCLC. In May of this year, IMDELLTRA™ received accelerated approval from the FDA and is currently marketed in the US for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The efficacy of YL201 monotherapy is encouraging in ES-SCLC. MediLink has announced the data of a Phase I/II clinical trial of YL201 in patients with advanced solid tumors including SCLC as a selected oral presentation at the ESMO Congress 2024. This clinical trial collaboration aims to explore the potential of the two innovative drugs in the treatment of ES-SCLC and offer a novel and synergetic mechanism of action for clinical benefit.
About ES-SCLC
SCLC is an aggressive high-grade neuroendocrine carcinoma with extremely poor outcomes [1]. SCLC comprises roughly 15% (~0.36 million new cases) of the 2.4 million new lung cancer cases worldwide each year [2].
Approximately two-thirds of patients with SCLC present with extensive-stage (ES) disease at diagnosis, featuring tumors with distant metastasis or exceeding an area that can be treated within a single radiation field [3-5]. Patients with ES-SCLC, compared with patients with limited-stage (LS-SCLC), manifested with worse prognosis as the median expected overall survival is ~12 months following initial therapy and a 5-year overall survival rate of 3% [6-8].
About YL201
YL201 is an innovative ADC that specifically targets B7-H3. B7-H3 is overexpressed on different malignant cells and cancer-initiating cells of various tumor types, but has a restricted expression in normal tissue [9], indicating its potential as an ADC drug target. YL201 has been developed by utilizing MediLink’s Tumor Microenvironment Activable LINker-payload (TMALIN®) conjugated with a highly specific B7-H3 antibody. Currently, YL201 is being investigated in four Phase I or II studies, including one global Phase I clinical study.
About IMDELLTRA™
IMDELLTRA™ is a first-in-class, targeted immunotherapy engineered by Amgen researchers that binds to both DLL3 on tumor cells and CD3 on T cells, activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell [10-11]. DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target [12-13].
Please see IMDELLTRA™ full Prescribing Information, including BOXED WARNINGS
About MediLink Therapeutics
MediLink Therapeutics, founded in 2020, is a clinical stage biotech company dedicated to developing conjugated drugs with global competitiveness. MediLink has developed its proprietary TMALIN® ADC technology platform, enabling the generation of homogeneous ADC with high drug-antibody ratio and improved therapeutic window for the treatment of solid tumors. MediLink aims to provide improved treatment options for global patients and address unmet medical needs. The company is headquartered in Suzhou, China and has established R&D sites in Shanghai, China and Boston, US.
Reference:
1. Badin F. Considerations for selecting second-line treatment in patients with progressive small cell lung cancer and the use of Lurbinectedin in this setting. Cancer Treat Res. Commun., 2024, 39, 100803.
2. a. Oronsky B, Abrouk N, Caroen S, et al. A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC). J Cancer. 2022; 13, 2945-2953.
b. World Health Organization. Lung. 2020. https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed on March 15, 2024.
c. Sabari JK, Lok BH, Laird JH, et al. Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol. 2017, 14, 549.
3. National Cancer Institute, Small cell lung cancer treatment (PDQ®) – health professional version, 2023. Available from: https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq. Accessed 13 March 2023.
4. American Cancer Society. Lung cancer – Small cell lung cancer stages. Available from: https://www.cancer.org/cancer/lung-cancer/detection diagnosis-staging/staging-sclc.html. Accessed 13 March 2023.
5. Cancer Research UK. Limited and extensive stage (small cell lung cancer). Available from: https://www.cancerresearchuk.org/about-cancer/lung cancer/stages-types-grades/limited-extensive. Accessed 13 March 2023.
6. American Cancer Society. Lung Cancer Survival Rates. www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/survival-rates.html. Accessed on September 4, 2024.
7. Liu SV, Reck M, Mansfield AS, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021, 39, 619.
8. Howlader N, Noone A, Krapcho M, Miller D, Brest A, Yu M, et al. SEER Cancer Statistics Review. National Cancer Institute.
9. Kontos F, Michelakos T, Kurokawa T, Sadagopan A, Schwab JH, Ferrone CR, Ferrone S. B7-H3: An Attractive Target for Antibody-based Immunotherapy. Clin Cancer Res., 2021, 27, 1227
10. Giffin MJ, Cooke K, Lobenhofer EK, et al. AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer. Clin Cancer Res., 2021, 27, 1526.
11. Baeuerle PA, Kufer P, Bargou R. BiTE: Teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther., 2009, 11, 22.
12. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med., 2023, 389, 2063.
13. Rojo F, Corassa M, Mavroudis D, et al. International real-world study of DLL3 expression in patients with small cell lung cancer. Lung Cancer., 2020, 147, 237.
SOURCE: MediLink Therapeutics
Post Views: 175
SUZHOU, China I October 7, 2024 I MediLink Therapeutics (Suzhou) Co., Ltd. (“MediLink”), a clinical-stage biotech company, today announced a global clinical trial collaboration and supply agreement with Amgen Inc. Amgen will lead a global clinical study to evaluate the therapeutic potential of the combination of MediLink’s B7-H3-targeting antibody-drug conjugate (ADC) YL201 and Amgen’s DLL3- and CD3-targeting bispecific T-cell engager (BiTE®) IMDELLTRA™ in extensive-stage small cell lung cancer (ES-SCLC) under the clinical trial collaboration and supply agreement. MediLink will provide the investigational drug YL201 for the combination study.
This open-label, global, multi-center Phase Ib clinical study is designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of this combination regimen in ES-SCLC patients.
Both YL201 and IMDELLTRA™ have shown potential in ES-SCLC. In May of this year, IMDELLTRA™ received accelerated approval from the FDA and is currently marketed in the US for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The efficacy of YL201 monotherapy is encouraging in ES-SCLC. MediLink has announced the data of a Phase I/II clinical trial of YL201 in patients with advanced solid tumors including SCLC as a selected oral presentation at the ESMO Congress 2024. This clinical trial collaboration aims to explore the potential of the two innovative drugs in the treatment of ES-SCLC and offer a novel and synergetic mechanism of action for clinical benefit.
About ES-SCLC
SCLC is an aggressive high-grade neuroendocrine carcinoma with extremely poor outcomes [1]. SCLC comprises roughly 15% (~0.36 million new cases) of the 2.4 million new lung cancer cases worldwide each year [2].
Approximately two-thirds of patients with SCLC present with extensive-stage (ES) disease at diagnosis, featuring tumors with distant metastasis or exceeding an area that can be treated within a single radiation field [3-5]. Patients with ES-SCLC, compared with patients with limited-stage (LS-SCLC), manifested with worse prognosis as the median expected overall survival is ~12 months following initial therapy and a 5-year overall survival rate of 3% [6-8].
About YL201
YL201 is an innovative ADC that specifically targets B7-H3. B7-H3 is overexpressed on different malignant cells and cancer-initiating cells of various tumor types, but has a restricted expression in normal tissue [9], indicating its potential as an ADC drug target. YL201 has been developed by utilizing MediLink’s Tumor Microenvironment Activable LINker-payload (TMALIN®) conjugated with a highly specific B7-H3 antibody. Currently, YL201 is being investigated in four Phase I or II studies, including one global Phase I clinical study.
About IMDELLTRA™
IMDELLTRA™ is a first-in-class, targeted immunotherapy engineered by Amgen researchers that binds to both DLL3 on tumor cells and CD3 on T cells, activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell [10-11]. DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target [12-13].
Please see IMDELLTRA™ full Prescribing Information, including BOXED WARNINGS
About MediLink Therapeutics
MediLink Therapeutics, founded in 2020, is a clinical stage biotech company dedicated to developing conjugated drugs with global competitiveness. MediLink has developed its proprietary TMALIN® ADC technology platform, enabling the generation of homogeneous ADC with high drug-antibody ratio and improved therapeutic window for the treatment of solid tumors. MediLink aims to provide improved treatment options for global patients and address unmet medical needs. The company is headquartered in Suzhou, China and has established R&D sites in Shanghai, China and Boston, US.
Reference:
1. Badin F. Considerations for selecting second-line treatment in patients with progressive small cell lung cancer and the use of Lurbinectedin in this setting. Cancer Treat Res. Commun., 2024, 39, 100803.
2. a. Oronsky B, Abrouk N, Caroen S, et al. A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC). J Cancer. 2022; 13, 2945-2953.
b. World Health Organization. Lung. 2020. https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed on March 15, 2024.
c. Sabari JK, Lok BH, Laird JH, et al. Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol. 2017, 14, 549.
3. National Cancer Institute, Small cell lung cancer treatment (PDQ®) – health professional version, 2023. Available from: https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq. Accessed 13 March 2023.
4. American Cancer Society. Lung cancer – Small cell lung cancer stages. Available from: https://www.cancer.org/cancer/lung-cancer/detection diagnosis-staging/staging-sclc.html. Accessed 13 March 2023.
5. Cancer Research UK. Limited and extensive stage (small cell lung cancer). Available from: https://www.cancerresearchuk.org/about-cancer/lung cancer/stages-types-grades/limited-extensive. Accessed 13 March 2023.
6. American Cancer Society. Lung Cancer Survival Rates. www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/survival-rates.html. Accessed on September 4, 2024.
7. Liu SV, Reck M, Mansfield AS, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021, 39, 619.
8. Howlader N, Noone A, Krapcho M, Miller D, Brest A, Yu M, et al. SEER Cancer Statistics Review. National Cancer Institute.
9. Kontos F, Michelakos T, Kurokawa T, Sadagopan A, Schwab JH, Ferrone CR, Ferrone S. B7-H3: An Attractive Target for Antibody-based Immunotherapy. Clin Cancer Res., 2021, 27, 1227
10. Giffin MJ, Cooke K, Lobenhofer EK, et al. AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer. Clin Cancer Res., 2021, 27, 1526.
11. Baeuerle PA, Kufer P, Bargou R. BiTE: Teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther., 2009, 11, 22.
12. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med., 2023, 389, 2063.
13. Rojo F, Corassa M, Mavroudis D, et al. International real-world study of DLL3 expression in patients with small cell lung cancer. Lung Cancer., 2020, 147, 237.
SOURCE: MediLink Therapeutics
Post Views: 175
