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718 Phase 1/2 study of PRO1160, a CD70-directed antibody-drug conjugate, in patients with advanced solid tumors and hematologic malignancies
  1. Benjamin Garmezy1,
  2. Swetha Kambhampati2,
  3. Brendan Curti3,
  4. Melissa Reimers4,
  5. Paolo Caimi5,
  6. Catherine Diefenbach6,
  7. Elisabeth Heath7,
  8. Eric Jonasch8,
  9. Stephen Park9,
  10. Noah Kornblum10,
  11. Weidong Li11,
  12. Ning Li12,
  13. Stephen Spurgeon13,
  14. Ulka N Vaishampayan14,
  15. Dingwei Ye15,
  16. Li Zhang16,
  17. Weili Zhao17,
  18. Zhu Chen18,
  19. Naomi Hunder19,
  20. Sharon Ma19,
  21. Eric Song19 and
  22. Justin A Call20
  1. 1Sarah Cannon Cancer Institute Nashville, Nashville, TN, USA
  2. 2City of Hope, Duarte, CA, USA
  3. 3Providence Cancer Institute, Franz Clinic, Portland, OR, USA
  4. 4Washington University in St. Louis, St Louis, MO, USA
  5. 5Cleveland Clinic Foundation, Cleveland, OH, USA
  6. 6New York University Langone School of Medicine, New York, NY, USA
  7. 7Karmanos Cancer Institute, Detroit, MI, USA
  8. 8The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  9. 9Levine Cancer Institute, Charlotte, NC, USA
  10. 10Montefiore Medical Center, New York, NY, USA
  11. 11Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
  12. 12Chinese Academy of Medical Sciences, Beijing, China
  13. 13Oregon Health and Sciences University, Portland, OR, USA
  14. 14University of Michigan, Ann Arbor, MI, USA
  15. 15Fudan University Shanghai Cancer Center, Shanghai, China
  16. 16Sun Yat-Sen University Cancer Center, Guangzhou, China
  17. 17Ruijin Hospital-Shanghai Jiaotong University School of Medicine, Shanghai, China
  18. 18ProfoundBio (Suzhou), Suzhou, Jiangsu, China
  19. 19ProfoundBio US Co., Woodinville, WA, USA
  20. 20START Mountain Region, West Valley City, UT, 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 PRO1160 is a novel antibody-drug conjugate (ADC) directed to CD70, an antigen mediating immuno-suppression that is overexpressed in multiple solid tumors and hematologic malignancies, with limited distribution in normal tissues. PRO1160 comprises (1) a human monoclonal antibody specific for CD70, (2) a protease-cleavable proprietary hydrophilic linker, and (3) exatecan, a topoisomerase 1 inhibitor. Comprehensive prior work demonstrated that the hydrophilic linker confers excellent physicochemical properties and pharmacokinetics (PK) across a range of payload mechanisms and is superior to conventional linkers on these critical parameters for ADCs. In addition, exatecan is broadly active in many tumor types, is membrane permeable, and is not a substrate of multidrug resistance pumps, thus likely lending strong bystander effects and durable treatment responses. PRO1160 is highly potent in cell-derived xenograft models of renal cell carcinoma (RCC), non-Hodgkin lymphoma (NHL), and nasopharyngeal carcinoma (NPC). PRO1160 also demonstrates marked antitumor activity in patient-derived xenograft models of diverse tumor sites, histologies, molecular subtypes, target expression levels, and Epstein Barr Virus status. PRO1160 is stable in circulation and displays PK characteristics indistinguishable from the parent antibody in rats. In a GLP toxicity study in cynomolgus monkeys, the primary PRO1160-related toxicity resided in the thymus and bone marrow, was consistent with exatecan toxicities, and was reversible.

Methods PRO1160–001 is an ongoing, open-label Phase 1/2 study to evaluate the safety, tolerability, PK, and antitumor activity of PRO1160 in patients with metastatic RCC, metastatic or relapsed NPC, or advanced relapsed/refractory NHL.

Patients must have measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or the Lugano Classification for NHL. Patients must also have previously received therapies known to confer clinical benefit unless considered ineligible, refused by the patient, or not available in the region.

PRO1160 is given by intravenous infusion on Day 1 of a 21-day cycle and treatment may continue until disease progression, unacceptable toxicity, or other reason for discontinuation. The primary objectives are to evaluate the safety and tolerability of PRO1160 and to identify the maximum tolerated dose, if reached, and recommended phase 2 dose (RP2D).

This study consists of 2 parts, Part A: dose-escalation and dose-level expansion, and Part B: 3 tumor-specific expansion cohorts (metastatic RCC, metastatic or relapsed NPC, and advanced relapsed/refractory NHL) treated at the RP2D. PK, immunogenicity, and antitumor activity will also be evaluated. The study is currently enrolling at sites in the US, with future enrollment in China planned ( NCT05721222).

Trial Registration NCT05721222

Ethics Approval The study obtained ethics approval (WCG Institutional Review Board; ID 20230476) 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

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