Phase Ia study of anti-NAPI2B antibody–drug conjugate lifastuzumab vedotin DNIB0600A in patients with non–small cell lung cancer and platinum-resistant ovarian cancer

David E. Gerber, Jeffrey R. Infante, Michael S. Gordon, Sarah B. Goldberg, Miguel Martín, Enriqueta Felip, Maria Martinez Garcia, Joan H. Schiller, David R. Spigel, Julie Cordova, Valerie Westcott, Yulei Wang, David S. Shames, Youn Jeong Choi, Robert Kahn, Randall C. Dere, Divya Samineni, Jian Xu, Kedan Lin, Katie WoodStephanie Royer-Joo, Vanessa Lemahieu, Eva Schuth, Anjali Vaze, Daniel Maslyar, Eric W. Humke, Howard A. Burris

Research output: Contribution to journalArticle

Abstract

Purpose: This phase I trial assessed the safety, tolerability, and preliminary antitumor activity of lifastuzumab vedotin (LIFA), an antibody–drug conjugate of anti-NaPi2b mAb (MNIB2126A) and a potent antimitotic agent (monomethyl auristatin E). Patients and Methods: LIFA was administered to patients with non–small cell lung cancer (NSCLC) and platinum-resistant ovarian cancer (PROC), once every 3 weeks, by intravenous infusion. The starting dose was 0.2 mg/kg in this 3+3 dose-escalation design, followed by cohort expansion at the recommended phase II dose (RP2D). Results: Overall, 87 patients were treated at doses between 0.2 and 2.8 mg/kg. The MTD was not reached; 2.4 mg/kg once every 3 weeks was selected as the RP2D based on overall tolerability profile. The most common adverse events of any grade and regardless of relationship to study drug were fatigue (59%), nausea (49%), decreased appetite (37%), vomiting (32%), and peripheral sensory neuropathy (29%). Most common treatment-related grade ≥3 toxicities among patients treated at the RP2D (n = 63) were neutropenia (10%), anemia (3%), and pneumonia (3%). The pharmacokinetic profile was dose proportional. At active doses ≥1.8 mg/kg, partial responses were observed in four of 51 (8%) patients with NSCLC and 11 of 24 (46%) patients with PROC per RECIST. All RECIST responses occurred in patients with NaPi2bhigh by IHC. The CA-125 biomarker assessed for patients with PROC dosed at ≥1.8 mg/kg showed 13 of 24 (54%) had responses (≥50% decline from baseline). Conclusions: LIFA exhibited dose-proportional pharmacokinetics and an acceptable safety profile, with encouraging activity in patients with PROC at the single-agent RP2D of 2.4 mg/kg.

Original languageEnglish (US)
Pages (from-to)364-372
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number2
DOIs
StatePublished - Jan 15 2020

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gerber, D. E., Infante, J. R., Gordon, M. S., Goldberg, S. B., Martín, M., Felip, E., Garcia, M. M., Schiller, J. H., Spigel, D. R., Cordova, J., Westcott, V., Wang, Y., Shames, D. S., Choi, Y. J., Kahn, R., Dere, R. C., Samineni, D., Xu, J., Lin, K., ... Burris, H. A. (2020). Phase Ia study of anti-NAPI2B antibody–drug conjugate lifastuzumab vedotin DNIB0600A in patients with non–small cell lung cancer and platinum-resistant ovarian cancer. Clinical Cancer Research, 26(2), 364-372. https://doi.org/10.1158/1078-0432.CCR-18-3965