Telisotuzumab Vedotin beim c-Met + nicht-kleinzelligen Lungenkarzinom

2021 ◽  
Vol 12 (06) ◽  
pp. 356-356
Author(s):  
Alexander Kretzschmar
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
World Conference ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Erste Ergebnisse ◽  
Antibody Drug

Telisotuzumab Vedotin ist das erste Anti-c-Met-Antikörper-Konjugat (antibody-drug conjugate; ADC) seiner Klasse. Es adressiert c- Met-verstärkte und c-Met-überexprimierende (c-Met +) Tumoren. Auf dem virtuellen WCLC 2021 (World Conference on Lung Cancer) wurden erste Ergebnisse einer Phase-II-Studie (NCT03539536) mit dem neuen ADC bei vorbehandelten Patienten mit fortgeschrittenem c-Met + nicht-kleinzelligen Lungenkarzinom (NSCLC) vorgestellt.

Therapy of advanced metastatic lung cancer with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase I/II clinical experience.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 2504-2504 ◽  
Author(s):  
Michael J. Guarino ◽  
Alexander Starodub ◽  
Gregory A. Masters ◽  
Rebecca Suk Heist ◽  
Wells A. Messersmith ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Clinical Experience ◽  
Metastatic Lung Cancer ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Metastatic Lung ◽  
Antibody Drug

Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Locally Advanced or Metastatic Breast Cancer

2014 ◽  
Vol 32 (32) ◽  
pp. 3619-3625 ◽  
Author(s):  
Johanna Bendell ◽  
Mansoor Saleh ◽  
April A.N. Rose ◽  
Peter M. Siegel ◽  
Lowell Hart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Transmembrane Protein ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

Purpose Glycoprotein NMB (gpNMB), a novel transmembrane protein overexpressed in 40% to 60% of breast cancers, promotes metastases in animal models and is a prognostic marker of a poor outcome in patients. The antibody-drug conjugate glembatumumab vedotin consists of a fully human anti-gpNMB monoclonal antibody, conjugated via a cleavable linker to monomethyl auristatin E. Glembatumumab vedotin is generally well tolerated, with observed objective responses in advanced melanoma. This is, to our knowledge, the first study of glembatumumab vedotin in breast cancer. Patients and Methods Eligible patients had advanced/metastatic breast cancer with at least two prior chemotherapy regimens, including taxane, anthracycline, and capecitabine. A standard 3+3 dose escalation was followed by a phase II expansion. Immunohistochemistry for gpNMB was performed retrospectively for patients with available tumor tissue. Results Forty-two patients were enrolled. Dose-limiting toxicity (DLT) consisted of worsening neuropathy at 1.34 mg/kg. After excluding patients with baseline neuropathy more than grade 1, no DLT occurred through 1.88 mg/kg (the phase II dose). The phase II primary activity end point was met (12-week progression-free survival [PFS12] = 9 of 27 patients; 33%). Sixteen of 19 (84%) patients tested had gpNMB-positive tumors. At the phase II dose, median PFS was 9.1 weeks for all patients, 17.9 weeks for patients with triple-negative breast cancer (TNBC), and 18.0 weeks for patients with gpNMB-positive tumors. Two patients had confirmed partial responses; both had gpNMB-positive tumors and one had TNBC. Conclusion Glembatumumab vedotin has an acceptable safety profile. Preliminary evidence of activity in treatment-resistant metastatic breast cancer requires confirmation, such as the phase II randomized trial (EMERGE) that also examines the relationship between activity and gpNMB distribution/intensity.

scholarly journals Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma

2014 ◽  
Vol 32 (32) ◽  
pp. 3659-3666 ◽  
Author(s):  
Patrick A. Ott ◽  
Omid Hamid ◽  
Anna C. Pavlick ◽  
Harriet Kluger ◽  
Kevin B. Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Advanced Melanoma ◽  
Weekly Schedule ◽  
Antibody Drug Conjugate ◽  
End Points ◽  
Drug Conjugate ◽  
Antibody Drug

Purpose The antibody-drug conjugate glembatumumab vedotin links a fully human immunoglobulin G2 monoclonal antibody against the melanoma-related glycoprotein NMB (gpNMB) to the potent cytotoxin monomethyl auristatin E. This study evaluated the safety and activity of glembatumumab vedotin in patients with advanced melanoma. Patients and Methods Patients received glembatumumab vedotin every 3 weeks (schedule 1) in a dose escalation and phase II expansion at the maximum-tolerated dose (MTD). Dosing during 2 of 3 weeks (schedule 2) and weekly (schedule 3) was also assessed. The primary end points were safety and pharmacokinetics. The secondary end points included antitumor activity, gpNMB expression, and immunogenicity. Results One hundred seventeen patients were treated using schedule 1 (n = 79), schedule 2 (n = 15), or schedule 3 (n = 23). The MTDs were 1.88, 1.5, and 1.0 mg/kg for schedules 1, 2, and 3, respectively. Grade 3/4 treatment-related toxicities that occurred in two or more patients included rash, neutropenia, fatigue, neuropathy, arthralgia, myalgia, and diarrhea. Three treatment-related deaths (resulting from pneumococcal sepsis, toxic epidermal necrolysis, and renal failure) occurred at doses exceeding the MTDs. In the schedule 1 phase II expansion cohort (n = 34), five patients (15%) had a partial response and eight patients (24%) had stable disease for ≥ 6 months. The objective response rate (ORR) was 2 of 6 (33%) for the schedule 2 MTD and 3 of 12 (25%) for the schedule 3 MTD. Rash was correlated with a greater ORR and improved progression-free survival. Conclusion Glembatumumab vedotin is active in advanced melanoma. The schedule 1 MTD (1.88 mg/kg once every 3 weeks) was associated with a promising ORR and was generally well tolerated. More frequent dosing was potentially associated with a greater ORR but increased toxicity.

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