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|Ref Type||Journal Article|
|Authors||Moore KN, Birrer MJ, Marsters J, Wang Y, Choi Y, Royer-Joo S, Lemahieu V, Armstrong K, Cordova J, Samineni D, Schuth E, Vaze A, Maslyar D, Humke EW, Hamilton EP, Liu JF|
|Title||Phase 1b study of anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) in patients with platinum-sensitive recurrent ovarian cancer.|
|Date||2020 Jun 11|
|Abstract Text||This study investigated the safety and tolerability of lifastuzumab vedotin (DNIB0600A) (LIFA), an antibody-drug conjugate, in patients with recurrent platinum-sensitive ovarian cancer (PSOC).In this open-label, multicenter phase 1b study, LIFA was administered intravenously once every 3 weeks (Q3W) with starting dose 1.2 mg/kg in a 3 + 3 dose-escalation scheme. All patients received carboplatin at dose AUC 6 mg/mL·min (AUC6) Q3W for up to 6 cycles. Dose expansion cohorts were enrolled ± bevacizumab 15 mg/kg Q3W.Patients received LIFA at 1.2, 1.8, and 2.4 mg (n = 4, 5, and 20, respectively) with carboplatin. The maximum tolerated dose was not reached. The recommended phase 2 dose (RP2D) was LIFA 2.4 mg/kg + carboplatin AUC6 (cycles 1-6), with or without bevacizumab 15 mg/kg. Twelve patients received RP2D with bevacizumab. All patients experienced ≥1 adverse event (AE). The most common treatment-related AEs were neutropenia, peripheral neuropathy, thrombocytopenia, nausea, fatigue, anemia, diarrhea, vomiting, hypomagnesaemia, aspartate aminotransferase increased, alanine aminotransferase increased, and alopecia. Thirty-four (83%) patients experienced grade ≥ 3 AEs, the most frequent of which were neutropenia and thrombocytopenia. Nine (22%) patients experienced serious AEs. Pulmonary toxicities (34%), considered a potential risk of LIFA, included one patient who discontinued study treatment due to grade 2 pneumonitis. The median duration of progression-free survival was 10.71 months (95% CI: 8.54, 13.86) with confirmed complete/partial responses in 24 (59%) patients. Pharmacokinetics of mono-therapy LIFA was similar in combination therapy.LIFA in combination with carboplatin ± bevacizumab demonstrated acceptable safety and encouraging activity in PSOC patients.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|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|
|Unknown unknown||ovarian cancer||not applicable||Bevacizumab + Carboplatin + DNIB0600A||Phase I||Actionable||In a Phase Ib trial, the combination of DNIB0600A (Lifastuzumab vedotin) and Paraplatin (carboplatin) with or without Avastin (bevacizumab) demonstrated safety in patients with recurrent ovarian cancer and resulted in an objective response rate (ORR) of 59% (24/41), with a median progression-free survival (PFS) of 10.7 months, while the combination with Avastin (bevacizumab) resulted in an ORR of 67% (8/12) and a median PFS of 13.9 months (PMID: 32534811; NCT01995188).||32534811|
|Unknown unknown||ovarian cancer||not applicable||Carboplatin + DNIB0600A||Phase I||Actionable||In a Phase Ib trial, the combination of DNIB0600A (Lifastuzumab vedotin) and Paraplatin (carboplatin) with or without Avastin (bevacizumab) demonstrated safety in patients with recurrent ovarian cancer and resulted in an objective response rate (ORR) of 59% (24/41), with a median progression-free survival (PFS) of 10.7 months, DNIB0600A (Lifastuzumab vedotin) at RP2D (2.4 mg/kg) with Paraplatin (carboplatin) resulted in an ORR of 50% (10/20) and a median PFS of 8.5 months (PMID: 32534811; NCT01995188).||32534811|