Article Text

Download PDFPDF

708 A phase 1/2 study of rinatabart sesutecan (PRO1184), a novel folate receptor alpha-directed antibody-drug conjugate, in patients with locally advanced and/or metastatic solid tumors
  1. Justin A Call1,
  2. Ian Anderson2,
  3. Ira Winer3,
  4. Douglas Orr4,
  5. Oladapo Yeku5,
  6. Debra L Richardson6,
  7. Jian Zhang7,
  8. Elizabeth Lee8,
  9. Gottfried Konecny9,
  10. Ning Li10,
  11. Sandip P Patel11,
  12. Lin Wu12,
  13. Jing Wang12,
  14. Jun Zhang13,
  15. Ying Cheng14,
  16. Xiaohua Wu7,
  17. Naomi Hunder15,
  18. Lian Lu16,
  19. Sharon Ma15,
  20. Eric Song15 and
  21. Erika Hamilton17
  1. 1START Mountain Region, West Valley City, UT, USA
  2. 2Providence Medical Center, Santa Rosa, CA, USA
  3. 3Wayne State University, Detroit, MI, USA
  4. 4Mary Crowley Cancer Research, Dallas, TX, USA
  5. 5Massachusetts General Hospital, Boston, MA, USA
  6. 6Stephenson Cancer Center, Oklahoma City, OK, USA
  7. 7Fudan University Shanghai Cancer Center, Shanghai, China
  8. 8Dana Farber Cancer Institute, Boston, MA, USA
  9. 9UCLA, Los Angeles, CA, USA
  10. 10Chinese Academy of Medical Sciences, Beijing, China
  11. 11University of California San Diego Moores Cancer Center, La Jolla, CA, USA
  12. 12Hunan Cancer Hospital, Changsha, China
  13. 13University of Kansas Medical Center, Kansas City, KS, USA
  14. 14Jilin Cancer Hospital, Changchun, China
  15. 15ProfoundBio US Co., Woodinville, WA, USA
  16. 16ProfoundBio (Suzhou) Co. Ltd, Suzhou, China
  17. 17Sarah Cannon Research Institute, Nashville, TN, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Rinatabart sesutecan (Rina-S) is an antibody-drug conjugate (ADC) consisting of a human monoclonal antibody that selectively binds FRα, a novel cleavable hydrophilic linker, and a topoisomerase 1 inhibitor payload, exatecan. The hydrophilic linker confers superior physicochemical properties and pharmacokinetics compared to conventional linkers in preclinical models. Rina-S exerts robust antitumor activity in mouse xenograft models of multiple tumor types with high, moderate, and low FRα expression, consistent with the broad potency and bystander activity of the exatecan payload. Here we present emerging data from the first-in-human trial (NCT05579366).

Methods PRO1184–001 is an ongoing, phase 1/2, open-label, dose escalation and expansion study. Eligible patients have locally advanced and/or metastatic/unresectable solid tumors, including epithelial ovarian cancer (EOC), endometrial cancer, non-small cell lung cancer (NSCLC), breast cancer, or mesothelioma. Patients must have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or mRECIST 1.1 for pleural mesothelioma. FRα tumor expression levels were retrospectively tested using the Ventana immunohistochemistry FOLR1 assay. Primary objectives are to identify the maximum tolerated dose, recommended phase 2 dose, and evaluate safety and tolerability.

Results As of 09 June 2023, 10 patients have been treated with Rina-S at 60 (n=3) and 120 (n=7) mg/m2. Tumor types included platinum-resistant/refractory EOC (n=5), endometrial cancer (n=2), NSCLC (n=2), and mesothelioma (n=1). Patients received a median of 4 (range, 1 to 9) prior treatments. Eight patients completed the DLT period and had post-baseline tumor assessments per RECIST. The other 2 patients, who had FRα-negative tumors, discontinued due to early clinical progression. Patients have received between 1 and 8 cycles and 5 remain on treatment.

The most common treatment-related adverse events (AEs) were nausea (n=5), decreased white blood cell counts (n=3), and fatigue, decreased lymphocyte counts, and decreased neutrophil counts (n=2 each); most events were Grade 1 or 2. Treatment-related ≥ Grade 3 hematologic AEs were reported for 2 patients treated at 120 mg/m2. No ocular toxicity or interstitial lung disease was observed. No DLTs were observed.

Antitumor activity was observed at both dose levels and in patients with high, medium, and low FRα expression, including an ongoing confirmed partial response in a patient with endometrial cancer and decreased tumor measurements in additional patients.

Conclusions Emerging data suggest a promising safety profile for Rina-S, with most AEs being mild or moderate and consistent with findings in preclinical studies. Antitumor activity has been observed at well tolerated dose levels. Dose escalation continues.

Trial Registration NCT05579366

Ethics Approval The study obtained ethics approval (WCG Institutional Review Board; ID 20223552) and participants gave informed consent prior to taking part.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.