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763 Initial results from phase I dose escalation trial of CAN1012 in patients with solid tumor malignancies
  1. Henry Yu1,
  2. Herui Yao2,
  3. Ning Li3,
  4. Shuhang Wang4,
  5. Brendan Curti5,
  6. Giorgio Massimini1,
  7. Ming-Hong Hu6,
  8. William L Redmond7,
  9. Rongliang Lou1,
  10. Wanping Geng8,
  11. Sanlong Wang1,
  12. Meiling Zhang1,
  13. Rongchu Chen1,
  14. Baotian Qin1,
  15. John Mao9,
  16. Shaoshan Wang10 and
  17. Erwei Song11
  1. 1CanWell Pharma Inc, Woburn, MA, USA
  2. 2Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
  3. 3Chinese Academy of Medical Sciences, Beijing, China
  4. 4Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  5. 5Providence Cancer Institute, Franz Clinic, Portland, OR, USA
  6. 6CanWell Pharma Inc., Woburn, MA, USA
  7. 7Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
  8. 8CanWell Pharma, Woburn, MA, USA
  9. 9JWM Pharma, San Francisco, CA, USA
  10. 10Canwell Pharma Inc, Newton, MA, USA
  11. 11Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
  • 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 CAN1012 is a selective Toll-like receptor 7 (TLR7) agonist whose receptor locates in intracellular endosomes of plasmacytoid dendritic cells (pDC). Upon binding to TLR7 agonist, pDC secret high levels of type I interferons and other anti-viral cytokines/chemokines.

Methods CAN1012 has been demonstrated to stimulate IFN-alpha releases in human PBMC in vitro and to produce antitumor effects, when given intratumorally (IT) in various syngeneic mouse tumor models in vivo. Furthermore, it can be used in combination with immune checkpoint inhibitors, anti-angiogenesis inhibitors or chemotherapy agents to enhance the anti-tumor effect. The exposure of CAN1012 in tumor tissues via IT route was over 1,000-fold higher than in blood, resulting in much less systemic toxicity. Pharmacodynamic studies revealed that it increased CD4+ and CD8+ T cell infiltration in the tumor microenvironment (TME), but decreased myeloid-derived suppressor cell (MDSCs) counts. It also has a favorable ADME/PK profile when administered subcutaneously in mice, rats and monkeys, and its pharmaceutical properties have also been optimized for IT administration.

Results Based on the superior safety and efficacy of CAN1012 in preclinical studies, a first in-human Phase I dose-escalation trial for advanced cancer patients was initiated in multi clinical centers both in US (NCT04987112) and China (CTR20222322), using intratumoral administration and a standard 3+3 trial design. Up to now, four dose cohorts were successfully administered in patients. Preliminary results indicated that CAN1012 is well-tolerated with no severe adverse effect documented. In addition, a favorable efficacy is observed in some of treated patients.

Conclusions The trial is still undergoing according to the initial design and is expected to be completed by the end of this year.

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