Abstract
Introduction
Lung-MAP S1400K was designed to evaluate the response to telisotuzumab vedotin, an
antibody-drug conjugate targeting c-MET, in patients with c-MET–positive squamous
cell carcinoma (SCC).
Patients and Methods
Patients with previously treated SCC with c-MET–positive tumors (H score ≥ 150, Ventana
SP44 assay) were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor-naive)
and Cohort 2 (immune checkpoint inhibitor refractory). Telisotuzumab vedotin 2.7 mg/kg
was administered intravenously every 3 weeks until disease progression or unacceptable
toxicity. Response assessments were performed every 6 weeks. The primary endpoint
was response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary
endpoints included progression-free survival, overall survival, response within cohort,
duration of response, and toxicities. Interim analysis was planned after 20 evaluable
patients, with ≥ 3 responses needed to continue enrollment.
Results
Forty-nine patients (14% of screened patients) were assigned to S1400K, 28 patients
enrolled (15 in Cohort 1 and 13 in Cohort 2), and 23 were eligible. S1400K closed
on December 21, 2018 owing to lack of efficacy. Two responses (response rate of 9%;
95% confidence interval, 0%-20%) were reported in cohort 1 (1 complete and 1 unconfirmed
partial response), whereas 10 patients had stable disease, with a disease control
rate of 52%. The median overall and progression-free survival was 5.6 and 2.4 months,
respectively. There were 3 grade 5 events (2 pneumonitis, in Cohort 2, and 1 bronchopulmonary
hemorrhage, in Cohort 1).
Conclusion
Telisotuzumab vedotin failed to meet the pre-specified response needed to justify
continuing enrollment to S1400K. Pneumonitis was an unanticipated toxicity observed
in patients with SCC.
Keywords
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Article info
Publication history
Published online: October 14, 2020
Accepted:
September 15,
2020
Received in revised form:
September 14,
2020
Received:
July 13,
2020
Identification
Copyright
© 2020 Elsevier Inc. All rights reserved.
