Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein–Overexpressing Advanced Nonsquamous <i>EGFR</i>-Wildtype Non–Small Cell Lung Cancer in the Phase II LUMINOSITY Trial-Reference-Cited by-同舟云学术

Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein–Overexpressing Advanced Nonsquamous EGFR-Wildtype Non–Small Cell Lung Cancer in the Phase II LUMINOSITY Trial

Published:2024-09-01 Issue:25 Volume:42 Page:3000-3011
ISSN:0732-183X
Container-title:Journal of Clinical Oncology
language:en
Short-container-title:JCO

Author:

Camidge D. Ross¹^ORCID,Bar Jair²^ORCID,Horinouchi Hidehito³^ORCID,Goldman Jonathan⁴^ORCID,Moiseenko Fedor⁵^ORCID,Filippova Elena⁶,Cicin Irfan⁷^ORCID,Ciuleanu Tudor⁸,Daaboul Nathalie⁹,Liu Chunling¹⁰,Bradbury Penelope¹¹,Moskovitz Mor¹²,Katgi Nuran¹³,Tomasini Pascale¹⁴,Zer Alona¹²^ORCID,Girard Nicolas¹⁵^ORCID,Cuppens Kristof¹⁶¹⁷^ORCID,Han Ji-Youn¹⁸^ORCID,Wu Shang-Yin¹⁹²⁰^ORCID,Baijal Shobhit²¹,Mansfield Aaron S.²²^ORCID,Kuo Chih-Hsi²³^ORCID,Nishino Kazumi²⁴^ORCID,Lee Se-Hoon²⁵^ORCID,Planchard David²⁶²⁷^ORCID,Baik Christina²⁸,Li Martha²⁹,Ansell Peter²⁹,Xia Summer²⁹,Bolotin Ellen²⁹,Looman Jim²⁹,Ratajczak Christine²⁹,Lu Shun³⁰^ORCID

Affiliation:

1. University of Colorado Cancer Center, Aurora, CO

2. Sheba Medical Center, Ramat Gan, Israel

3. National Cancer Center Hospital, Tokyo, Japan

4. David Geffen School of Medicine at UCLA, Los Angeles, CA

5. St Petersburg Napalkov Cancer Center, St Petersburg, Russia

6. Center of Palliative Medicine De Vita, St Petersburg, Russia

7. Istinye University Medical Center, Istanbul, Turkey

8. Institutul Oncologic, Cluj-Napoca, Romania

9. Centre intégré de cancérologie de la Montérégie (CICM), Charles-LeMoyne Hospital, University of Sherbrooke, Quebec, QC, Canada

10. The Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang, China

11. Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

12. Davidoff Cancer Center, Beilinson, Petah-Tikva, Israel

13. Dr Suat Seren Chest Diseases and Chest Surgery Training and Research Hospital, Health Sciences University, Izmir, Yenisehir, Turkey

14. Aix Marseille University, APHM, INSERM, CNRS, CRCM, Hôpital Nord, Multidisciplinary Oncology and Therapeutic Innovations Department, Marseille, France

15. Départment d’Oncologie Médicale, Institut Curie, Paris, France

16. Department of Pulmonology and Thoracic Oncology, Jessa Hospital, Hasselt, Belgium

17. Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium

18. National Cancer Center, Goyang-si, Gyeonggi-do, South Korea

19. Department of Oncology, National Cheng Kung University Hospital, Tainan, Taiwan

20. College of Medicine, National Cheng Kung University, Tainan, Taiwan

21. University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom

22. Mayo Clinic, Rochester, MN

23. Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan

24. Osaka International Cancer Institute, Osaka, Japan

25. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

26. Gustave Roussy, Department of Medical Oncology, Villejuif, France

27. Faculty of Medicine, Paris-Saclay University, Paris, France

28. Fred Hutchinson Cancer Center, from Seattle Cancer Care Alliance, Seattle, WA

29. AbbVie Inc, North Chicago, IL

30. Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Abstract

PURPOSE Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536 ) aimed to identify the optimal c-Met protein–overexpressing non–small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor ( EGFR)-wildtype NSCLC. METHODS Eligible patients had locally advanced/metastatic c-Met protein–overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous EGFR-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%–<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review. RESULTS In total, 172 patients with nonsquamous EGFR-wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%). CONCLUSION Teliso-V was associated with durable responses in c-Met protein–overexpressing nonsquamous EGFR-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.

Publisher

American Society of Clinical Oncology (ASCO)

Link

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.24.00720

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