Reference Detail

Ref Type

Journal Article

PMID

(31540980)

Authors

Gerber DE, Infante JR, Gordon MS, Goldberg SB, Martín M, Felip E, Martinez Garcia M, Schiller JH, Spigel DR, Cordova J, Westcott V, Wang Y, Shames DS, Choi Y, Kahn R, Dere RC, Samineni D, Xu J, Lin K, Wood K, Royer-Joo S, Lemahieu V, Schuth E, Vaze A, Maslyar D, Humke EW, Burris HA

Title

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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	26	2	2020 01 15	364-372	Clin Cancer Res

URL

Abstract Text

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).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).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).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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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
DNIB0600A	DNIB0600A	0	1

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
DNIB0600A		Lifastuzumab vedotin\|RG-7599		DNIB0600A (Lifastuzumab vedotin) is an antibody-drug conjugate consists of an antibody targeting SLC34A2 and monomethyl auristatin E, which may lead to disruption of the microtubule network in SLC34A2-expressing cancer cells, thereby potentially inhibiting cell proliferation (PMID: 29401246, PMID: 32534811, PMID: 31540980).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References