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
  • 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. [email protected].
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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