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

XMT-1536 is a first-in-class ADC targeting NaPi2b, the sodium-dependent phosphate transport protein, broadly expressed in solid tumors such as serous epithelial ovarian cancer. XMT-1536 is being evaluated in patients (pts) with ovarian cancer and non-small cell lung adenocarcinoma in a phase I study (NCT03319628) and has shown a favorable safety profile and evidence of clinical activity. Here, we report on the safety and efficacy of XMT-1536 in pts with platinum-resistant ovarian cancer in the expansion portion of the phase I study. The expansion study is enrolling pts with platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal cancer with up to 3 prior lines of therapy and pts with 4 prior lines of therapy regardless of platinum status. Doses of 36 and 43 mg/m2 administered intravenously every 4 weeks (q4w) are being evaluated. Tumor tissue will be retrospectively evaluated for NaPi2b expression. As of 01-May-2020, 27 pts with ovarian cancer have enrolled: median age was 70 years (range 55 to 85); median prior lines of therapy was 3 (range 1 to 5); >50% had received prior bevacizumab and/or a PARP inhibitor. Twelve pts were dosed at 36 mg/m2 and 15 pts were dosed at 43 mg/m2, the MTD determined in dose escalation. The most frequently (≥20%) reported treatment-related adverse events were fatigue, nausea, vomiting, pyrexia, decreased appetite, diarrhea, and transient increase in AST. As of 01-May-2020, 20 pts were evaluable for response assessment. Treatment with XMT-1536 yielded 2 complete and 5 partial responses with an objective response rate of 35% and disease control rate of 80%, with a favorable trend toward response in tumors with higher NaPi2b expression. Data on safety, response, duration of response, and correlation of response with NaPi2b expression will be presented. At the time of presentation data will be updated with a data cut off of August 2020 and include additional pts and longer follow up for currently enrolled pts. XMT-1536 treatment at 36 and 43 mg/m2 q4w has shown a favorable safety profile and antitumor activity in ovarian cancer. These data support further clinical development of XMT-1536.