2. Academic Validation
  3. 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

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

  • Clin Cancer Res. 2020 Jan 15;26(2):364-372. doi: 10.1158/1078-0432.CCR-18-3965.
David E Gerber 1,  Jeffrey R Infante 2,  Michael S Gordon 3,  Sarah B Goldberg 4,  Miguel Martín 5,  Enriqueta Felip 6,  Maria Martinez Garcia 7,  Joan H Schiller 8,  David R Spigel 9,  Julie Cordova 10,  Valerie Westcott 10,  Yulei Wang 10,  David S Shames 10,  YounJeong Choi 10,  Robert Kahn 10,  Randall C Dere 10,  Divya Samineni 10,  Jian Xu 10,  Kedan Lin 10,  Katie Wood 10,  Stephanie Royer-Joo 10,  Vanessa Lemahieu 10,  Eva Schuth 10,  Anjali Vaze 10,  Daniel Maslyar 10,  Eric W Humke 10,  Howard A Burris 3rd 11
Affiliations

Affiliations

  • 1 Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.
  • 2 Janssen Pharmaceuticals, Inc., Raritan, New Jersey.
  • 3 HonorHealth Research Institute, Scottsdale, Arizona.
  • 4 Yale School of Medicine, New Haven, Connecticut.
  • 5 Instituto De Investigacion Sanitaria Gregorio Marañon, Ciberonc, Universidad Complutense, Madrid, Spain.
  • 6 Vall d'Hebron Institute of Oncology, Barcelona, Spain.
  • 7 Hospital del Mar, Barcelona, Spain.
  • 8 Inova Fairfax Hospital, Annandale, Virginia.
  • 9 Sarah Cannon Research Institute, Nashville, Tennessee.
  • 10 Genentech, Inc., South San Francisco, California.
  • 11 Sarah Cannon Research Institute, Nashville, Tennessee. howard.burris@SarahCannon.com.
PMID: 31540980 DOI: 10.1158/1078-0432.CCR-18-3965
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 NaPi2b-high 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.

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