Figure 6 from ETx-22, a Novel Nectin-4–Directed Antibody–Drug Conjugate, Demonstrates Safety and Potent Antitumor Activity in Low-Nectin-4–Expressing Tumors
Authors: Lopez Marc , Crompot Emerence , Josselin Emmanuelle , Farina Anne , Rubis Marion , Castellano Remy , Fares Joanna , Wehbe Maria , Collette Yves , Charafe Emmanuelle , Blanchin Stéphanie , Romagne François , Pálfi Anikó , Hechler Torsten , Pahl Andreas , Azim Hatem A. , Lhospice Florence , Mamessier Emilie , Bertucci François , Elands Jack , Préville Xavier , Olive Daniel 
Published: November 2024

<p><i>In vivo</i> efficacy of ETx-22 in SUM190 breast cancer cell line and PDX models. <b>A,</b> NSG mice (<i>n</i> = 5/group) were orthotopically xenografted bilaterally with SUM190PT cells embedded in Matrigel. At the indicated time (black arrowhead), three different ADCs were injected intravenously: isotype control (8 mg/kg) conjugated to maleimide–ß-glucuronide–exatecan–PSAR (open diamonds), ETx-22 (from chimeric 15A7.5 mAb) at 4 and 8 mg/kg (open and plain blue arrowheads, respectively), and EV at 4 mg/kg (plain brown arrowhead). <b>B,</b> Same as in A but NSG mice (<i>n</i> = 5/group) were orthotopically xenografted bilaterally with MMAE-resistant SUM190 cells embedded in Matrigel. Statistical significance between groups is indicated at the termination day of control group (<i>P</i> < 0.0001). The number of complete responses in the 8 mg/kg ETx-22 group is indicated. <b>C,</b> NMRI nude mice (<i>n</i> = 8/group) were subcutaneously implanted with tumor fragments from bladder cancer PDX B521. At the indicated time (black arrowhead), three different ADCs were injected intravenously: isotype control (8 mg/kg) conjugated to maleimide–ß-glucuronide–exatecan–PSAR (open diamonds), ETx-22 (from chimeric 15A7.5) at 4 and 10 mg/kg (open and plain blue arrowheads, respectively), and EV at 4 mg/kg (plain brown arrowhead). A chemotherapy control group (red diamonds) was treated with cisplatin (4 mg/kg, Q3W) plus gemcitabine (60 mg/kg, QW × 4). <b>D,</b> Same as in <b>C</b> with tumor fragments from bladder cancer PDX BLCU-003. ADC treatments were administered twice (black arrowheads). ETx-22 was from humanized 15A7.5 mAb. <b>E,</b> NSG mice (<i>n</i> = 5/group) were orthotopically xenografted bilaterally with TNBC317 tumor. At the indicated time (black arrowhead), three different ADCs were injected intravenously: isotype control (4 mg/kg) conjugated to maleimide–ß-glucuronide–exatecan–PSAR (open diamonds), ETx-22 (from chimeric 15A7.5) at 4 mg/kg (plain blue arrowheads), and EV at 4 mg/kg (plain brown arrowhead). <b>F,</b> Same as in <b>E</b> with TNBC348 tumor. Etx-22 and its isotype control were administered at 1 mg/kg and EV at 4 mg/kg. <b>G,</b> NOD/SCID mice (<i>N</i> = 10/ group) subcutaneously implanted with tumor fragments from ovarian cancer PDX OV2018. At the indicated time (black arrowhead), three different ADCs were injected intravenously: isotype control (10 mg/kg) conjugated to maleimide–ß-glucuronide–exatecan–PSAR (open diamonds), ETx-22 (from chimeric 15A7.5) at 4 mg/kg (plain blue arrowhead), and EV at 4 mg/kg (plain brown arrowhead). A chemotherapy control group (red diamonds) was treated with carboplatin (40 mg/kg, QW × 4). <b>H,</b> Same as in <b>G</b> with tumor fragments from ovarian cancer PDX OV2423. ADC treatments were administered twice (black arrowheads). ETx-22 was from humanized 15A7.5 mAb. In each animal model, (i) control group (plain black diamonds) received ADC diluent; (ii) tumor growth was monitored twice a week using a caliper, and tumor volume was calculated in mm<sup>3</sup> as <i>L</i> × <i>W</i><sup>2</sup> × π/6; and (iii) the <i>H</i>-score for nectin-4 expression as determined by IHC staining is indicated. Statistical significance between groups is indicated at the termination day of the control group (*, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ****, <i>P</i> < 0.0001). On each graph, the number of complete responses in the highest-dosed ETx-22 group is indicated. CR, Complete Remission; d, day; QS, Quick Score.</p>