Anti-NaPi2b antibody–drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study

Banerjee, Susana; Oza, Amit M.; Birrer, Michael J.; Hamilton, Erika; Hasan, Jurjees; Leary, Alexandra; Moore, Kathleen N.; Maćkowiak-Matejczyk, Beata; Pikiel, Joanna; Ray‐Coquard, Isabelle; Trask, Peter C.; Lin, Kedan; Schuth, Eva; Vaze, Anjali; Choi, Youn Jeong; Marsters, Jim; Maslyar, Daniel; Lemahieu,; Y, Wang; Humke, Eric W.; Liu, J F

doi:10.1093/annonc/mdy023

Cited by 71 publications

(32 citation statements)

References 18 publications

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“…A percentage of patients in this study (24%, 10 of 41) developed treatment-induced ADA, also seen in other studies [18,19,25]. Characterization by competitive binding indicated that the antibody responses of these patients were directed primarily against the antibody and linker-drug.…”

Section: Discussionsupporting

confidence: 80%

“…In animal studies, conjugation to an anti-NaPi2b monoclonal antibody improved the tolerability of MMAE and widened its therapeutic window [17]. We have previously reported LIFA study results from a phase 1a trial with NSCLC and platinum-resistant ovarian cancer patients (PROC) [18], and a phase 2 trial with PROC patients [19]. Here, we report results of a phase 1b study of LIFA in combination with chemotherapy in patients with PSOC.…”

Section: Introductionmentioning

confidence: 98%

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Phase 1b study of anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) in patients with platinum-sensitive recurrent ovarian cancer

Moore

Birrer

Marsters³

et al. 2020

Gynecologic Oncology

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• Lifastuzumab vedotin DNIB0600A (LIFA) is an anti-NaPi2b antibody conjugated to a potent anti-mitotic agent (MMAE). • This phase Ib study investigated LIFA in patients with recurrent platinum-sensitive ovarian cancer. • LIFA in combination with carboplatin has an acceptable safety profile when administered by IV infusion Q3W. • Overall confirmed objective responses were observed in 59% and CA-125 responses in 81% of evaluable patients. • Response rate and duration of response are important factors for evaluation of antibody-drug conjugates in ovarian cancers.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 98%

Phase 1b study of anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) in patients with platinum-sensitive recurrent ovarian cancer

Moore

Birrer

Marsters³

et al. 2020

Gynecologic Oncology

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“…All clinical trials were conducted in accordance with the Declaration of Helsinki and in compliance with good clinical practice guidelines and quality assurance procedures. More details on the studies included in the data set can be found in the previous clinical publications …”

Section: Methodsmentioning

confidence: 99%

“…More details on the studies included in the data set can be found in the previous clinical publications. [14][15][16][17][18] Modeling software The model was developed using the nonlinear mixedeffects modeling software (NONMEM), version 7.4 (ICON Development Solutions, Ellicott City, MD). The first-order conditional estimation with interaction combined with the Laplace method was used for parameter estimations.…”

Section: Platinum-resistant Ovarian Cancer Data Setmentioning

confidence: 99%

A New Method to Model and Predict Progression Free Survival Based on Tumor Growth Dynamics

Yu¹,

Wang²,

Kågedal³

2020

CPT Pharmacom & Syst Pharma

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Progression‐free survival (PFS) has been increasingly used as a primary endpoint for early clinical development. The aim of the present work was to develop a model where target lesion dynamics and risk for nontarget progression are jointly modeled for predicting PFS. The model was developed based on a pooled platinum‐resistant ovarian cancer dataset comprising four different treatments and a wide range of dose levels. The target lesion progression was derived from tumor growth dynamics based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The nontarget progression hazard was correlated to the first derivative of target lesion tumor size with respect to time. The PFS time was determined by the first occurring event, target lesion progression, or nontarget progression. The final joint model not only captured target lesion tumor growth dynamics but also predicted PFS well. A similar approach can potentially be used to predict PFS in future oncology studies.

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“…13-38; M. Williams, Table 3; refs. [39][40][41][42][43][44][45][46][47][48][49][50]. A positive association between target expression and clinical activity (target-response relationship; TRR) was based on findings where there was higher frequency of objective response rates (ORRs) in target-expressing patients.…”

Section: Study Identification and Categorizationmentioning

confidence: 99%

Patient Selection Strategies to Maximize Therapeutic Index of Antibody–Drug Conjugates: Prior Approaches and Future Directions

Williams

Spreafico

Vashisht

et al. 2020

Molecular Cancer Therapeutics

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Antibody-drug conjugates (ADC) are targeted agents that have shown promise in treating cancer. A central challenge in development of ADCs is the relatively narrow therapeutic index observed in clinical studies. Patient selection strategies based on expression of the target in tumors have the potential to maximize benefit and provide the best chance of clinical success; however, implementation of biomarker-driven trials can be difficult both practically and scientifically. We conducted a survey of recent clinical experience from early-phase ADC trials completed between 2000 and 2019 to evaluate the different approaches to patient selection currently being used and assess whether there is evidence that target expression is associated with clinical activity. Our analysis of patient selection strategies indicates that optimal trial design for early-stage trials should be based on multiple factors, including prevalence and heterogeneity of target expression among intent-to-treat patients, as well as biological factors influencing expression of cell surface and soluble target. To ensure a high probability of success, early implementation of patient selection strategies centered around target expression are pivotal to development of ADCs. In this review, we propose a strategic approach that can be applied for optimization of trial design.

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Anti-NaPi2b antibody–drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study

Abstract: NCT01991210.

Cited by 71 publications

References 18 publications

Phase 1b study of anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) in patients with platinum-sensitive recurrent ovarian cancer

Phase 1b study of anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) in patients with platinum-sensitive recurrent ovarian cancer

A New Method to Model and Predict Progression Free Survival Based on Tumor Growth Dynamics

Patient Selection Strategies to Maximize Therapeutic Index of Antibody–Drug Conjugates: Prior Approaches and Future Directions

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