Advertisement

Targeting NaPi2b in ovarian cancer

Published:November 14, 2022DOI:https://doi.org/10.1016/j.ctrv.2022.102489

      Highlights

      • NaPi2b is expressed in malignant tissues with minimal expression in healthy tissues (85/85).
      • NaPi2b is a targetable biomarker with stable expression throughout disease course (72/85).
      • Archival tissue samples are sufficient to assess NaPi2b expression (68/85).
      • Robust diagnostic assays can be developed to reliably detect NaPi2b expression (80/85).
      • Early trials with NaPi2b antibody-drug conjugates in ovarian cancer are promising (83/85).

      Abstract

      Novel biomarkers are needed to direct new treatments for ovarian cancer, a disease for which the standard of care remains heavily focused on platinum-based chemotherapy. Despite the success of PARP inhibitors, treatment options are limited, particularly in the platinum-resistant setting. NaPi2b is a cell surface sodium-dependent phosphate transporter that regulates phosphate homeostasis under normal physiological conditions and is a lineage marker that is expressed in select cancers, including ovarian, lung, thyroid, and breast cancers, with limited expression in normal tissues. Based on its increased expression in ovarian tumors, NaPi2b is a promising candidate to be studied as a biomarker for treatment and patient selection in ovarian cancer. In preclinical studies, the use of antibodies against NaPi2b showed that this protein can be exploited for tumor mapping and therapeutic targeting. Emerging data from phase 1 and 2 clinical trials in ovarian cancer have suggested that NaPi2b can be successfully detected in patient biopsy samples using immunohistochemistry, and the NaPi2b-targeting antibody-drug conjugate under evaluation appeared to elicit therapeutic responses. The aim of this review is to examine literature supporting NaPi2b as a novel biomarker for potential treatment and patient selection in ovarian cancer and to discuss the critical next steps and future analyses necessary to drive the study of this biomarker and therapeutic targeting forward.

      Keywords

      To read this article in full you will need to make a payment
      ESMO Member Login
      Login with your ESMO username and password.
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Forster I.C.
        • Hernando N.
        • Biber J.
        • Murer H.
        Phosphate transporters of the SLC20 and SLC34 families.
        Mol Aspects Med. 2013; 34: 386-395
        • Marks J.
        The role of SLC34A2 in intestinal phosphate absorption and phosphate homeostasis.
        Pflugers Arch. 2019; 471: 165-173
        • Beck L.
        • Karaplis A.C.
        • Amizuka N.
        • Hewson A.S.
        • Ozawa H.
        • Tenenhouse H.S.
        Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities.
        Proc Natl Acad Sci U S A. 1998; 95: 5372-5377
        • Bergwitz C.
        • Roslin N.M.
        • Tieder M.
        • Loredo-Osti J.C.
        • Bastepe M.
        • Abu-Zahra H.
        • et al.
        SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis.
        Am J Hum Genet. 2006; 78: 179-192
        • Custer M.
        • Lotscher M.
        • Biber J.
        • Murer H.
        • Kaissling B.
        Expression of Na-P(i) cotransport in rat kidney: localization by RT-PCR and immunohistochemistry.
        Am J Physiol. 1994; 266: F767-F774
        • Feild J.A.
        • Zhang L.
        • Brun K.A.
        • Brooks D.P.
        • Edwards R.M.
        Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine.
        Biochem Biophys Res Commun. 1999; 258: 578-582
        • Hilfiker H.
        • Hattenhauer O.
        • Traebert M.
        • Forster I.
        • Murer H.
        • Biber J.
        Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine.
        Proc Natl Acad Sci U S A. 1998; 95: 14564-14569
        • Nishimura M.
        • Naito S.
        Tissue-specific mRNA expression profiles of human solute carrier transporter superfamilies.
        Drug Metab Pharmacokinet. 2008; 23: 22-44
        • Xu H.
        • Bai L.
        • Collins J.F.
        • Ghishan F.K.
        Molecular cloning, functional characterization, tissue distribution, and chromosomal localization of a human, small intestinal sodium-phosphate (Na+-Pi) transporter (SLC34A2).
        Genomics. 1999; 62: 281-284
        • Homann V.
        • Rosin-Steiner S.
        • Stratmann T.
        • Arnold W.H.
        • Gaengler P.
        • Kinne R.K.
        Sodium-phosphate cotransporter in human salivary glands: molecular evidence for the involvement of NPT2b in acinar phosphate secretion and ductal phosphate reabsorption.
        Arch Oral Biol. 2005; 50: 759-768
        • Traebert M.
        • Hattenhauer O.
        • Murer H.
        • Kaissling B.
        • Biber J.
        Expression of type II Na-P(i) cotransporter in alveolar type II cells.
        Am J Physiol. 1999; 277: L868-L873
        • Sabbagh Y.
        • O'Brien S.P.
        • Song W.
        • Boulanger J.H.
        • Stockmann A.
        • Arbeeny C.
        • et al.
        Intestinal Npt2b plays a major role in phosphate absorption and homeostasis.
        J Am Soc Nephrol. 2009; 20: 2348-2358
        • Saito A.
        • Nikolaidis N.M.
        • Amlal H.
        • Uehara Y.
        • Gardner J.C.
        • LaSance K.
        • et al.
        Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment.
        Sci Transl Med. 2015; 7: 313ra181
        • Shibasaki Y.
        • Etoh N.
        • Hayasaka M.
        • Takahashi M.O.
        • Kakitani M.
        • Yamashita T.
        • et al.
        Targeted deletion of the type IIb Na(+)-dependent Pi-co-transporter, NaPi-IIb, results in early embryonic lethality.
        Biochem Biophys Res Commun. 2009; 381: 482-486
        • Chen H.
        • Xu H.
        • Dong J.
        • Li J.
        • Ghishan F.K.
        Tumor necrosis factor-alpha impairs intestinal phosphate absorption in colitis.
        Am J Physiol Gastrointest Liver Physiol. 2009; 296: G775-G781
        • Corut A.
        • Senyigit A.
        • Ugur S.A.
        • Altin S.
        • Ozcelik U.
        • Calisir H.
        • et al.
        Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis.
        Am J Hum Genet. 2006; 79: 650-656
        • Huqun I.S.
        • Miyazawa H.
        • Ishii K.
        • Uchiyama B.
        • Ishida T.
        • et al.
        Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis.
        Am J Respir Crit Care Med. 2007; 175: 263-268
        • Bodyak N.D.
        • Mosher R.
        • Yurkovetskiy A.V.
        • Yin M.
        • Bu C.
        • Conlon P.R.
        • et al.
        The dolaflexin-based antibody-drug conjugate XMT-1536 targets the solid tumor lineage antigen SLC34A2/NaPi2b.
        Mol Cancer Ther. 2021; 20: 896-905
        • Chen D.R.
        • Chien S.Y.
        • Kuo S.J.
        • Teng Y.H.
        • Tsai H.T.
        • Kuo J.H.
        • et al.
        SLC34A2 as a novel marker for diagnosis and targeted therapy of breast cancer.
        Anticancer Res. 2010; 30: 4135-4140
        • Gryshkova V.
        • Goncharuk I.
        • Gurtovyy V.
        • Khozhayenko Y.
        • Nespryadko S.
        • Vorobjova L.
        • et al.
        The study of phosphate transporter NAPI2B expression in different histological types of epithelial ovarian cancer.
        Exp Oncol. 2009; 31: 37-42
        • Jarzab B.
        • Wiench M.
        • Fujarewicz K.
        • Simek K.
        • Jarzab M.
        • Oczko-Wojciechowska M.
        • et al.
        Gene expression profile of papillary thyroid cancer: sources of variability and diagnostic implications.
        Cancer Res. 2005; 65: 1587-1597
        • Lin K.
        • Rubinfeld B.
        • Zhang C.
        • Firestein R.
        • Harstad E.
        • Roth L.
        • et al.
        Preclinical development of an anti-NaPi2b (SLC34A2) antibody-drug conjugate as a therapeutic for non-small cell lung and ovarian cancers.
        Clin Cancer Res. 2015; 21: 5139-5150
        • Mattes M.J.
        • Look K.
        • Furukawa K.
        • Pierce V.K.
        • Old L.J.
        • Lewis Jr, J.L.
        • et al.
        Mouse monoclonal antibodies to human epithelial differentiation antigens expressed on the surface of ovarian carcinoma ascites cells.
        Cancer Res. 1987; 47: 6741-6750
        • Rubin S.C.
        • Kairemo K.J.
        • Brownell A.L.
        • Daghighian F.
        • Federici M.G.
        • Pentlow K.S.
        • et al.
        High-resolution positron emission tomography of human ovarian cancer in nude rats using 124I-labeled monoclonal antibodies.
        Gynecol Oncol. 1993; 48: 61-67
        • Rubin S.C.
        • Kostakoglu L.
        • Divgi C.
        • Federici M.G.
        • Finstad C.L.
        • Lloyd K.O.
        • et al.
        Biodistribution and intraoperative evaluation of radiolabeled monoclonal antibody MX35 in patients with epithelial ovarian cancer.
        Gynecol Oncol. 1993; 51: 61-66
        • Yin B.W.
        • Kiyamova R.
        • Chua R.
        • Caballero O.L.
        • Gout I.
        • Gryshkova V.
        • et al.
        Monoclonal antibody MX35 detects the membrane transporter NaPi2b (SLC34A2) in human carcinomas.
        Cancer Immun. 2008; 8: 3
        • Levan K.
        • Mehryar M.
        • Mateoiu C.
        • Albertsson P.
        • Back T.
        • Sundfeldt K.
        Immunohistochemical evaluation of epithelial ovarian carcinomas identifies three different expression patterns of the MX35 antigen, NaPi2b.
        BMC Cancer. 2017; 17: 303
        • Rangel L.B.
        • Sherman-Baust C.A.
        • Wernyj R.P.
        • Schwartz D.R.
        • Cho K.R.
        • Morin P.J.
        Characterization of novel human ovarian cancer-specific transcripts (HOSTs) identified by serial analysis of gene expression.
        Oncogene. 2003; 22: 7225-7232
        • Shyian M.
        • Gryshkova V.
        • Kostianets O.
        • Gorshkov V.
        • Gogolev Y.
        • Goncharuk I.
        • et al.
        Quantitative analysis of SLC34A2 expression in different types of ovarian tumors.
        Exp Oncol. 2011; 33: 94-98
        • Bondeson D.P.
        • Paolella B.R.
        • Asfaw A.
        • Rothberg M.V.
        • Skipper T.A.
        • Langan C.
        • et al.
        Phosphate dysregulation via the XPR1-KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer. Nat.
        Cancer. 2022;
        • Hong S.H.
        • Minai-Tehrani A.
        • Chang S.H.
        • Jiang H.L.
        • Lee S.
        • Lee A.Y.
        • et al.
        Knockdown of the sodium-dependent phosphate co-transporter 2b (NPT2b) suppresses lung tumorigenesis.
        PLoS ONE. 2013; 8: e77121
        • Jin H.
        • Xu C.X.
        • Lim H.T.
        • Park S.J.
        • Shin J.Y.
        • Chung Y.S.
        • et al.
        High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling.
        Am J Respir Crit Care Med. 2009; 179: 59-68
        • Russo-Abrahao T.
        • Lacerda-Abreu M.A.
        • Gomes T.
        • Cosentino-Gomes D.
        • Carvalho-de-Araujo A.D.
        • Rodrigues M.F.
        • et al.
        Characterization of inorganic phosphate transport in the triple-negative breast cancer cell line, MDA-MB-231.
        PLoS ONE. 2018; 13: e0191270
        • Elias K.M.
        • Emori M.M.
        • Westerling T.
        • Long H.
        • Budina-Kolomets A.
        • Li F.
        • et al.
        Epigenetic remodeling regulates transcriptional changes between ovarian cancer and benign precursors. JCI.
        Insight. 2016; : 1
        • Reddy J.
        • Fonseca M.A.S.
        • Corona R.I.
        • Nameki R.
        • Segato Dezem F.
        • Klein I.A.
        • et al.
        Predicting master transcription factors from pan-cancer expression data.
        Sci Adv. 2021; 7: eabf6123
        • Chaves-Moreira D.
        • Mitchell M.A.
        • Arruza C.
        • Rawat P.
        • Sidoli S.
        • Nameki R.
        • et al.
        The transcription factor PAX8 promotes angiogenesis in ovarian cancer through interaction with SOX17.
        Sci Signal. 2022; 15: eabm2496
      1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Ovarian Cancer. https://seer.cancer.gov/statfacts/html/ovary.html. Accessed July 14, 2022.

        • Siegel R.L.
        • Miller K.D.
        • Fuchs H.E.
        • Jemal A.
        Cancer statistics, 2022.
        CA Cancer J Clin. 2022; 72: 7-33
        • Sung H.
        • Ferlay J.
        • Siegel R.L.
        • Laversanne M.
        • Soerjomataram I.
        • Jemal A.
        • et al.
        Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J Clin. 2021; 71: 209-249
        • Dochez V.
        • Caillon H.
        • Vaucel E.
        • Dimet J.
        • Winer N.
        • Ducarme G.
        Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review.
        J Ovarian Res. 2019; 12: 28
        • Lheureux S.
        • Braunstein M.
        • Oza A.M.
        Epithelial ovarian cancer: evolution of management in the era of precision medicine.
        CA Cancer J Clin. 2019; 69: 280-304
        • Luvero D.
        • Milani A.
        • Ledermann J.A.
        Treatment options in recurrent ovarian cancer: latest evidence and clinical potential.
        Ther Adv Med Oncol. 2014; 6: 229-239
        • Manzano A.
        • Ocana A.
        Antibody-drug conjugates: a promising novel therapy for the treatment of ovarian cancer.
        Cancers (Basel). 2020; : 12
        • Pujade-Lauraine E.
        • Banerjee S.
        • Pignata S.
        Management of platinum-resistant, relapsed epithelial ovarian cancer and new drug perspectives.
        J Clin Oncol. 2019; 37: 2437-2448
        • Miller R.E.
        • Leary A.
        • Scott C.L.
        • Serra V.
        • Lord C.J.
        • Bowtell D.
        • et al.
        ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer.
        Ann Oncol. 2020; 31: 1606-1622
        • Mirza M.R.
        • Coleman R.L.
        • Gonzalez-Martin A.
        • Moore K.N.
        • Colombo N.
        • Ray-Coquard I.
        • et al.
        The forefront of ovarian cancer therapy: update on PARP inhibitors.
        Ann Oncol. 2020; 31: 1148-1159
        • Radu M.R.
        • Pradatu A.
        • Duica F.
        • Micu R.
        • Cretoiu S.M.
        • Suciu N.
        • et al.
        Ovarian cancer: biomarkers and targeted therapy.
        Biomedicines. 2021; : 9
        • Tew W.P.
        • Lacchetti C.
        • Ellis A.
        • Maxian K.
        • Banerjee S.
        • Bookman M.
        • et al.
        PARP inhibitors in the management of ovarian cancer: ASCO guideline.
        J Clin Oncol. 2020; 38: 3468-3493
        • Gaillard S.
        • Oaknin A.
        • Ray-Coquard I.
        • Vergote I.
        • Scambia G.
        • Colombo N.
        • et al.
        Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: a multicenter, randomized, controlled, open-label phase 3 study (CORAIL).
        Gynecol Oncol. 2021; 163: 237-245
        • Luvero D.
        • Plotti F.
        • Aloisia A.
        • Montera R.
        • Terranova C.
        • Carlo De Cicco N.
        • et al.
        Ovarian cancer relapse: from the latest scientific evidence to the best practice.
        Crit Rev Oncol Hematol. 2019; 140: 28-38
        • Moore K.N.
        • Oza A.M.
        • Colombo N.
        • Oaknin A.
        • Scambia G.
        • Lorusso D.
        • et al.
        Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I.
        Ann Oncol. 2021; 32: 757-765
        • Pujade-Lauraine E.
        • Fujiwara K.
        • Ledermann J.A.
        • Oza A.M.
        • Kristeleit R.
        • Ray-Coquard I.L.
        • et al.
        Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study.
        Lancet Oncol. 2021; 22: 1034-1046
        • Pujade-Lauraine E.
        • Hilpert F.
        • Weber B.
        • Reuss A.
        • Poveda A.
        • Kristensen G.
        • et al.
        Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial.
        J Clin Oncol. 2014; 32: 1302-1308
      2. Bevacizumab [package insert]. South San Francisco, CA: Genentech Inc. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125085s0169lbl.pdf. May, 2009.

        • Atallah G.A.
        • Abd Aziz N.H.
        • Teik C.K.
        • Shafiee M.N.
        • Kampan N.C.
        New predictive biomarkers for ovarian cancer.
        Diagnostics (Basel). 2021; : 11
        • Bartoletti M.
        • Musacchio L.
        • Giannone G.
        • Tuninetti V.
        • Bergamini A.
        • Scambia G.
        • et al.
        Emerging molecular alterations leading to histology-specific targeted therapies in ovarian cancer beyond PARP inhibitors.
        Cancer Treat Rev. 2021; 101102298
        • Patel A.
        • Cowden E.
        • Okeke N.
        • Skende O.
        • Krassnoff P.
        • Alexander M.
        • et al.
        Abstracts: Pathobiology and Emerging Techniques (1145–1171).
        Modern Pathol. 2022; 2022: 1259
        • Finstad C.L.
        • Lloyd K.O.
        • Federici M.G.
        • Divgi C.
        • Venkatraman E.
        • Barakat R.R.
        • et al.
        Distribution of radiolabeled monoclonal antibody MX35 F(ab')2 in tissue samples by storage phosphor screen image analysis: evaluation of antibody localization to micrometastatic disease in epithelial ovarian cancer.
        Clin Cancer Res. 1997; 3: 1433-1442
        • Lopes dos Santos M.
        • Yeda F.P.
        • Tsuruta L.R.
        • Horta B.B.
        • Pimenta Jr., A.A.
        • Degaki T.L.
        • et al.
        Rebmab200, a humanized monoclonal antibody targeting the sodium phosphate transporter NaPi2b displays strong immune mediated cytotoxicity against cancer: a novel reagent for targeted antibody therapy of cancer.
        PLoS ONE. 2013; 8: e70332
      3. Drapkin R, Jung E, Bradshaw C, DeMars L, Mosher R. Evaluation of NaPi2b expression in a well-annotated longitudinal tissue series of ovarian serous carcinomas. International Gynecologic Cancer Society (IGCS) Annual Meeting. 2022.

        • Richardson D.L.
        • Barve M.
        • Saltos A.
        • Papadopoulos K.P.
        • Hays J.L.
        • Tolcher A.
        • et al.
        Comparison of NaPi2b expression from paired tissue samples in a clinical study of upifitamab rilsodotin (UpRi; XMT-1536) supports a strategy of testing in archival material.
        Int Gynecol Cancer Soc (IGCS) Annual Meeting. 2022;
        • Moore K.N.
        • Martin L.P.
        • O'Malley D.M.
        • Matulonis U.A.
        • Konner J.A.
        • Perez R.P.
        • et al.
        Safety and activity of mirvetuximab soravtansine (IMGN853), a folate receptor alpha-targeting antibody-drug conjugate, in platinum-resistant ovarian, fallopian Tube, or primary peritoneal cancer: A phase I expansion study.
        J Clin Oncol. 2017; 35: 1112-1118
        • Moore K.N.
        • Oza A.M.
        • Colombo N.
        • Oaknin A.
        • Scambia G.
        • Lorusso D.
        • et al.
        FORWARD I (GOG 3011): A phase III study of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), versus chemotherapy in patients (pts) with platinum-resistant ovarian cancer (PROC).
        Ann Oncol. 2019; 30 (Oral presentation (abstract 992O))
        • Moore K.N.
        • Van Gorp T.
        • Wang J.
        • Esteves B.
        • Zweidler-McKay P.A.
        MIRASOL (GOG 3045/ENGOT OV-55): A randomized, open-label, phase III study of mirvetuximab soravtansine versus investigator’s choice of chemotherapy in advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate-alpha (FRα) expression.
        J Clin Oncol. 2020; 38 (abstract TPS6103)
        • Cree I.A.
        • Deans Z.
        • Ligtenberg M.J.
        • Normanno N.
        • Edsjo A.
        • Rouleau E.
        • et al.
        Guidance for laboratories performing molecular pathology for cancer patients.
        J Clin Pathol. 2014; 67: 923-931
        • Akhtar M.
        • Rashid S.
        • Al-Bozom I.A.
        PD-L1 immunostaining: what pathologists need to know.
        Diagn Pathol. 2021; 16: 94
        • Zhang H.
        • Moisini I.
        • Ajabnoor R.M.
        • Turner B.M.
        • Hicks D.G.
        Applying the new guidelines of HER2 testing in breast cancer.
        Curr Oncol Rep. 2020; 22: 51
        • Detre S.
        • Saclani Jotti G.
        • Dowsett M.
        A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas.
        J Clin Pathol. 1995; 48: 876-878
        • Wolff A.C.
        • Hammond M.E.H.
        • Allison K.H.
        • Harvey B.E.
        • Mangu P.B.
        • Bartlett J.M.S.
        • et al.
        Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice guideline focused update.
        J Clin Oncol. 2018; 36: 2105-2122
        • Tong J.T.W.
        • Harris P.W.R.
        • Brimble M.A.
        • Kavianinia I.
        An insight into FDA approved antibody-drug conjugates for cancer therapy.
        Molecules. 2021; 26
        • Banerjee S.
        • Oza A.M.
        • Birrer M.J.
        • Hamilton E.P.
        • Hasan J.
        • Leary A.
        • et al.
        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.
        Ann Oncol. 2018; 29: 917-923
        • Gerber D.E.
        • Infante J.R.
        • Gordon M.S.
        • Goldberg S.B.
        • Martin M.
        • Felip E.
        • et al.
        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; 26: 364-372
        • Moore K.N.
        • Birrer M.J.
        • Marsters J.
        • Wang Y.
        • Choi Y.
        • Royer-Joo S.
        • et al.
        Phase 1b study of anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) in patients with platinum-sensitive recurrent ovarian cancer.
        Gynecol Oncol. 2020; 158: 631-639
        • Mosher R.
        • Poling L.L.
        • Qin L.
        • Bodyak N.
        • Bergstrom D.
        Relationship of NaPi2b expression and efficacy of XMT-1536, a NaPi2b targeting antibody-drug conjugate (ADC), in an unselected panel of human primary ovarian mouse xenograft models.
        Mol Cancer Ther. 2018; 17
        • Hamilton E.P.
        • Barve M.A.
        • Tolcher A.W.
        • Buscema J.
        • Papadopoulos K.P.
        • Zarwan C.
        • et al.
        Safety and efficacy of XMT-1536 in ovarian cancer: a subgroup analysis from the phase I expansion study of XMT-1536, a NaPi2b antibody-drug conjugate.
        Ann Oncol. 2020; 31: S627-S628
        • Richardson D.L.
        • Hamilton E.P.
        • Barve M.
        • Anderson C.K.
        • Taylor S.K.
        • Lakhani N.
        • et al.
        Updated results from the phase 1b expansion study of upifitamab rilsodotin (UpRi; MT-1536), a NaPi2b-directed dolaflexin antibody drug conjugate (ADC) in ovarian cancer. Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s.
        Cancer. 2022;
        • Tolcher A.W.
        • Varkey Ulahannan S.
        • Papadopoulos K.P.
        • Edenfield W.J.
        • Matulonis U.A.
        • Burns T.F.
        • et al.
        Phase 1 dose escalation study of XMT-1536, a novel NaPi2b-targeting antibody-drug conjugate (ADC), in patients (pts) with solid tumors likely to express NaPi2b.
        J Clin Oncol. 2019; 37
      4. NCT03319628. First-in-human study of XMT-1536 in cancers likely to express NaPi2b. https://clinicaltrials.gov/ct2/show/record/NCT0331962. Accessed July 14, 2022.

      5. Richardson DL, Perez Fidalgo JA, Gonzalez-Martin A, Oaknin A, Hamilton E, Hays JL, et al. UPLIFT (ENGOT-ov67/GOG-3048): A Pivotal Cohort of the XMT-1536-1 Trial of Upifitamab Rilsodotin (XMT-1536; UpRi), a NaPi2b-directed Antibody-Drug Conjugate (ADC), in Platinum-Resistant Ovarian Cancer. Presented at the International Gynecologic Cancer Society, New York. . 2022.

      6. NCT04907968. Study of upifitamab rilsodotin in combination with other agent(s) in participants with high-grade serous ovarian cancer (UPGRADE). https://clinicaltrials.gov/ct2/show/record/NCT0490796. Accessed July 14, 2022.

      7. Hays JL, Werner TL, Lakhani N, Edenfield J, Friedman C, Taylor SE, et al. UPGRADE: Phase 1 Combination Trial of the NaPi2b-directed Antibody-Drug Conjugate (ADC) Upifitamab Rilsodotin (UpRi; XMT-1536) in Patients With Ovarian Cancer. Presented at the International Gynecologic Cancer Society, New York. 2022.

      8. NCT05329545. Upifitamab rilsodotin maintenance in platinum-sensitive recurrent ovarian cancer (UP-NEXT). https://clinicaltrials.gov/ct2/show/record/NCT05329545. Accessed July 14, 2022.

      9. Richardson DL, Philip H, O’Malley DM, Gonzalez-Martin A, Herzog TJ, Rogalski C, et al. UP-NEXT (GOG-3049/ENGOT-ov71-NSGO-CTU): A Study of Upifitamab Rilsodotin (UpRi), a NaPi2b-directed Antibody-Drug Conjugate (ADC) in Platinum-Sensitive Recurrent Ovarian Cancer. Presented at the International Gynecologic Cancer Society, New York. 2022.