TY - JOUR
T1 - 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
AU - Gerber, David E.
AU - Infante, Jeffrey R.
AU - Gordon, Michael S.
AU - Goldberg, Sarah B.
AU - Martín, Miguel
AU - Felip, Enriqueta
AU - Garcia, Maria Martinez
AU - Schiller, Joan H.
AU - Spigel, David R.
AU - Cordova, Julie
AU - Westcott, Valerie
AU - Wang, Yulei
AU - Shames, David S.
AU - Choi, Youn Jeong
AU - Kahn, Robert
AU - Dere, Randall C.
AU - Samineni, Divya
AU - Xu, Jian
AU - Lin, Kedan
AU - Wood, Katie
AU - Royer-Joo, Stephanie
AU - Lemahieu, Vanessa
AU - Schuth, Eva
AU - Vaze, Anjali
AU - Maslyar, Daniel
AU - Humke, Eric W.
AU - Burris, Howard A.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2020/1/15
Y1 - 2020/1/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-18-3965
DO - 10.1158/1078-0432.CCR-18-3965
M3 - Article
C2 - 31540980
AN - SCOPUS:85077918701
SN - 1078-0432
VL - 26
SP - 364
EP - 372
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -