Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study

Coleman, Robert L.; Lorusso, Domenica; Gennigens, Christine; González-Martín, Antonio; Randall, Leslie M.; Cibula, David; Lund, Bente; Woelber, Linn; Pignata, Sandro; Forget, Fréd́eric; Redondo, Andrés; Vindeløv, Signe Diness; Chen, Menghui; Harris, Jeffrey R.; Smith, Margaret S.; Nicacio, Leonardo; Teng, Melinda S L; Laenen, Annouschka; Rangwala, Reshma; Manso, Luís; Mirza, Mansoor Raza; Monk, Bradley J.; Vergote, Ignace; Raspagliesi, Francesco; Melichar, Bohuslav; Garcia, Lydia Gaba; Jackson, A.; Henry, Stéphanie; Král, Zdeněk; Harter, Philipp; Giorgi, Ugo De; Bjurberg, Maria; Gold, Michael A.; O’Malley, David M.; Honhon, Brigitte; Vulsteke, Christof; Cuypere, Eveline De; Denys, Hannelore; Baurain, Jean‐François; Zamagni, Claudio; Tenney, Meaghan; Gordinier, Mary E.; Bradley, William H.; Schlumbrecht, Matthew; Spirtos, Nicola M.; Concin, Nicole; Mahner, Sven; Scambia, Giovanni; Leath, Charles A.; Farias‐Eisner, Robin; Cohen, Joshua M.; Muller, Carolyn; Bhatia, Sumeet

doi:10.1016/s1470-2045(21)00056-5

Cited by 209 publications

(247 citation statements)

References 31 publications

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“…3 F ). Another criterion for our candidate selection was that EGFR and TF are currently explored as ADC targets in clinical trials, and previous studies pointed at their potential as treatment targets in cancer ( 26 – 31 ). We next performed immunofluorescence stainings of available matched patient tumors for EGFR, TF, BCAN, CD81, and MCT2.…”

Section: Resultsmentioning

confidence: 99%

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization

Governa

Talbot

Oliveira

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Therapeutic strategies directed at the tumor surfaceome (TS), including checkpoint inhibitor blocking antibodies, antibody drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cells, provide a new armament to fight cancer. However, a remaining bottleneck is the lack of strategies to comprehensively interrogate patient tumors for potential TS targets. Here, we have developed a platform (tumor surfaceome mapping [TS-MAP]) integrated with a newly curated TS classifier (SURFME) that allows profiling of primary 3D cultures and intact patient glioma tumors with preserved tissue architecture. Moreover, TS-MAP specifically identifies proteins capable of endocytosis as tractable targets for ADCs and other modalities requiring toxic payload internalization. In high-grade gliomas that remain among the most aggressive forms of cancer, we show that cellular spatial organization (2D vs. 3D) fundamentally transforms the surfaceome and endocytome (e.g., integrins, proteoglycans, semaphorins, and cancer stem cell markers) with general implications for target screening approaches, as exemplified by an ADC targeting EGFR. The TS-MAP platform was further applied to profile the surfaceome and endocytome landscape in a cohort of freshly resected gliomas. We found a highly diverse TS repertoire between patient tumors, not directly associated with grade and histology, which highlights the need for individualized approaches. Our data provide additional layers of understanding fundamental to the future development of immunotherapy strategies, as well as procedures for proteomics-based target identification and selection. The TS-MAP platform should be widely applicable in efforts aiming at a better understanding of how to harness the TS for personalized immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization

Governa

Talbot

Oliveira

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…In this study, patients who had never received prior bevacizumab demonstrated better efficacy compared to patients who had been treated with prior bevacizumab. Prior treatment with bevacizumab has been associated with reduced clinical activity of subsequent cancer therapies in multiple treatment settings and with different mechanisms of actions [19][20][21][22][23]. Additionally, preclinical studies evaluating the effects of pre-administration of anti-VEGF antibodies on the pharmacokinetics and tissue distribution of other antibodies did demonstrate a reduced accumulation of trastuzumab in breast cancer tumor-bearing mice [24].…”

Section: Discussionmentioning

confidence: 99%

Phase 1b study of AVB-500 in combination with paclitaxel or pegylated liposomal doxorubicin platinum-resistant recurrent ovarian cancer

Fuh

Bookman

Liu

et al. 2021

Gynecologic Oncology

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The combination of AVB-500 plus chemotherapy was safe and tolerable with no DLTs identified.• At the AVB-500 RP2D (15 mg/kg), AVB-500+PAC demonstrated better clinical activity than AVB-500+PLD.• Patients with no prior bevacizumab had greater clinical response than those with prior bevacizumab and historical control.• An exposure-response relationship was identified for AVB-500 trough levels >13.8 mg/L exhibiting greater clinical response.• A pretreatment serum biomarker may identify patients who benefit from AVB-500 in combination with chemotherapy.

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“…In late September 2021, the FDA granted accelerated approval to Tivdak ® (tisotumab vedotin-tftv), deeming it the most recently approved ADC on the market. Tivdak ® , codeveloped by Seagen and Genmab, is the first and only approved ADC indicated for treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy [111,112]. This is the third FDA approved ADC for Seagen, further cementing their dominance as the industry leader in ADC technologies.…”

Section: Tivdak ®mentioning

confidence: 99%

An Insight into FDA Approved Antibody-Drug Conjugates for Cancer Therapy

et al. 2021

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The large number of emerging antibody-drug conjugates (ADCs) for cancer therapy has resulted in a significant market ‘boom’, garnering worldwide attention. Despite ADCs presenting huge challenges to researchers, particularly regarding the identification of a suitable combination of antibody, linker, and payload, as of September 2021, 11 ADCs have been granted FDA approval, with eight of these approved since 2017 alone. Optimism for this therapeutic approach is clear, despite the COVID-19 pandemic, 2020 was a landmark year for deals and partnerships in the ADC arena, suggesting that there remains significant interest from Big Pharma. Herein we review the enthusiasm for ADCs by focusing on the features of those approved by the FDA, and offer some thoughts as to where the field is headed.

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Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study

Cited by 209 publications

References 31 publications

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization

Phase 1b study of AVB-500 in combination with paclitaxel or pegylated liposomal doxorubicin platinum-resistant recurrent ovarian cancer

An Insight into FDA Approved Antibody-Drug Conjugates for Cancer Therapy

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