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Topline results from the single-arm Phase 2 LUMINOSITY trial evaluating telisotuzumab vedotin (Teliso-V; previously known as ABBV-399) in patients with c-Met protein overexpression, epidermal growth factor receptor (EGFR) wild type, advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) demonstrated compelling clinical benefits across key endpoints, including overall response rate (ORR) per independent central review (ICR) of 35% and 23% across c-Met High and c-Met Intermediate patients, respectively.

In addition, other endpoints demonstrated meaningful clinical outcomes including median duration of response per ICR of 9 months and 7.2 months and a median overall survival of 14.6 months and 14.2 months across c-Met High and c-Met Intermediate patients respectively.

The safety profile of telisotuzumab vedotin was consistent with previous findings and no new safety concerns were identified.

Adverse events with telisotuzumab vedotin monotherapy were generally well managed and tolerated.

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Study Design
The LUMINOSITY trial (M14-239), is an ongoing Phase 2 study designed to identify the target NSCLC populations that overexpress c-Met best suited for telisotuzumab vedotin monotherapy in the second line or third line setting, and then to expand the groups to further evaluate efficacy in the selected populations.

The endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS).

A full data set from the LUMINOSITY study will be presented at a future medical meeting and we will discuss with global health authorities the potential to support an accelerated approval.

Leading cause of cancer-related deaths
Approximately 85% of lung cancers are classified as NSCLC [1] and despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths in both men and women throughout the world. [2] C-Met protein overexpression is found in approximately 25% of advanced EGFR wild type NSCLC patients [3] and is associated with a poor prognosis for these patients.[4][5][6]

Telisotuzumab vedotin, an investigational,  first-in-class, c-Met protein directed Antibody-drug Conjugate (ADC), is being studied in this patient population who have very limited treatment options and where there are currently no approved therapies. The drug, which is composed of a c-Met antibody (ABT-700) and a microtubule inhibitor ( or MMAE), is designed to targeting c-Met overexpressing tumors.

C-Met is a receptor tyrosine kinase that is overexpressed in many solid tumors including NSCLC.

Telisotuzumab vedotin is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type non squamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01, which is currently enrolling. In addition, telisotuzumab vedotin is being evaluated in combination with osimertinib in the ongoing Phase 1 study M14-237, and as a monotherapy in the Phase 2 LUMINOSITY study.

“The results of the Phase 2 LUMINOSITY trial are encouraging for those patients with non-small cell lung cancer with c-Met overexpression as there is a critical need for better care and additional therapy options for them,” noted Ross Camidge, MD, PhD, University of Colorado Cancer Center, United States, and Principal Investigator for the trial.

“Today’s announcement also provides confidence as we continue to enroll patients into the Phase 3 TeliMET NSCLC-01 trial and expand our understanding of telisotuzumab vedotin’s potential,” Camidge added.

“Results from the Phase 2 LUMINOSITY trial mark an important step forward for AbbVie’s mission to advance new oncology treatments across our ADC program targeting solid tumor types with critical patient needs,” explained Roopal Thakkar, M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie.

Telisotuzumab vedotin is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type nonsquamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01, which is currently enrolling.

Breakthrough Therapy Designation
Telisotuzumab vedotin has also been granted several designations around the world including Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) and Taiwanese health authorities, SAKIGAKE designation in Japan by the Ministry of Health, Labour and Welfare (MHLW), as well as being awarded an Innovation Passport by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

Clinical trials
Study of Telisotuzumab Vedotin (ABBV-399) in Participants With Previously Treated c-Met+ Non-Small Cell Lung Cancer – ClinicalTrials.gov ID NCT03539536
A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC) – ClinicalTrials.gov ID – NCT04928846
A Study Evaluating the Safety, Pharmacokinetics (PK), and Preliminary Efficacy of ABBV-399 in Participants With Advanced Solid Tumors – ClinicalTrials.gov ID – NCT02099058

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Osimertinib (Tagrisso®; AstraZeneca) Prescribing Information

References
[1] National Cancer Institute. Non-small cell lung cancer treatment – health professional version. https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq#_37_toc. Accessed December 8, 2021.
[2] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum in: CA Cancer J Clin. 2020 Jul;70(4):313. PMID: 30207593.
[3] Ansell PJ, Baijal S, Liede A, et al. Prevalence and Characterization of c-MET–Overexpressing Non-small Cell Lung Cancer (NSCLC) Across Clinical Trial Samples and Real-world Patient Cohorts From the City of Hope National Medical Center. Cancer Research UK (CRUK) – Lung Cancer Conference; Manchester, UK2022.
[4] Liang H, Wang M. MET Oncogene in Non-Small Cell Lung Cancer: Mechanism of MET Dysregulation and Agents Targeting the HGF/c-Met Axis. Onco Targets Ther. 2020;13:2491-510.
[5] Park S, Choi YL, Sung CO, et al. High MET copy number and MET overexpression: poor outcome in non-small cell lung cancer patients. Histol Histopathol. 2012;27(2):197-207.
[6] Guo B, Cen H, Tan X, et al. Prognostic value of MET gene copy number and protein expression in patients with surgically resected non-small cell lung cancer: a meta-analysis of published literatures. PLoS One. 2014;9(6):e99399.

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