Abstract 836P
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
NCT03319628.
Editorial acknowledgement
Legal entity responsible for the study
Mersana Therapeutics, Inc.
Funding
Mersana Therapeutics, Inc.
Disclosure
E.P. Hamilton: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (institution): Mersana Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Silverback Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Blackdiamond; Advisory/Consultancy: NanoString; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Hutchison MediPharma; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): StemCentrx; Research grant/Funding (institution): Curis; Research grant/Funding (institution): Verastem; Research grant/Funding (institution): Zymeworks; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Rgenix; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): TapImmune; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): H3 Biomedicine. A.W. Tolcher: Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (institution): Ascentage Pharma; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): EMD Serano; Advisory/Consultancy, Research grant/Funding (institution): BioInvent; Advisory/Consultancy, Research grant/Funding (institution): Adagene; Advisory/Consultancy, Research grant/Funding (institution): ADC Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Agenus; Advisory/Consultancy: Aximmune; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Boston Biomedical; Advisory/Consultancy: Forbius; Advisory/Consultancy: HBM Partners; Advisory/Consultancy: Mekanistic; Advisory/Consultancy, Research grant/Funding (institution): NBE Therapeutics; Advisory/Consultancy: Nuvalent; Advisory/Consultancy: Pelican; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Scimetex; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): Symphogen; Advisory/Consultancy: Syneos; Advisory/Consultancy: Immunome; Advisory/Consultancy: Abgenomics; Advisory/Consultancy: Glide Healthcare Partners; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Immunomet; Advisory/Consultancy: Menarini; Advisory/Consultancy, Research grant/Funding (institution): Mirati Therapeutics. K.P. Papadopoulos: Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): ArQule; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): ADC Therapeutics; Research grant/Funding (institution): ARMO Biosciences; Research grant/Funding (institution): Calithera Biosciences; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): 3D Medicines; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): F-Star; Research grant/Funding (institution): Formation Biologics; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Jounce Therapeutics; Research grant/Funding (institution): Linnaeus Therapeutics; Research grant/Funding (institution): MabSpace Biosciences; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Mersana; Research grant/Funding (institution): Mirati; Research grant/Funding (institution): Peloton Therapeutics; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Syros Pharmaceuticals; Research grant/Funding (institution): Tempest Therapeutics. C. Zarwan: Advisory/Consultancy: Revere Therapeutics; Non-remunerated activity/ies: Perceptive Informatics. D. Doroshow: Honoraria (self), Travel/Accommodation/Expenses: Ipsen; Honoraria (self): Boehringer Ingelheim. D. Huebner: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Mersana Therapeutics. V.M. Jansen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Mersana Therapeutics; Shareholder/Stockholder/Stock options: Eli Lilly and Company. D. Jarlenski: Leadership role, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Mersana Therapeutics; Shareholder/Stockholder/Stock options: Vertex; Shareholder/Stockholder/Stock options: Momenta Therapeutics; Shareholder/Stockholder/Stock options: Gilead; Shareholder/Stockholder/Stock options: Merck. R. Mosher: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Mersana Therapeutics; Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Spouse/Financial dependant: Novartis. J. Kaufman: Shareholder/Stockholder/Stock options, Full/Part-time employment: Mersana Therapeutics. K.N. Moore: Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy: Aravive; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (institution): GSK/Tesaro; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Immunogen; Advisory/Consultancy: Mersana; Advisory/Consultancy: Merck; Advisory/Consultancy: Tarveda; Advisory/Consultancy: VBL Therapeutics; Leadership role: GOG Foundation; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Forty Seven Inc; Research grant/Funding (institution): Immunocore; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): PTC Therapeutics; Research grant/Funding (institution): Lilly. D.L. Richardson: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Ipsen; Advisory/Consultancy, Research grant/Funding (institution): Mersana; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Advisory/Consultancy, Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Aravive; Research grant/Funding (institution): ArQule; Research grant/Funding (institution): Five Prime Therapeutics; Research grant/Funding (institution): Harpoon Therapeutics; Research grant/Funding (institution): Hookipa Biotech; Research grant/Funding (institution): Innovent Biologics; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Syros Pharmaceuticals. All other authors have declared no conflicts of interest.