Article Text

Download PDFPDF

608 Results of a phase 1 study investigating camidanlumab tesirine as monotherapy and in combination with pembrolizumab in patients with selected advanced solid tumors
  1. Christopher T Chen1,
  2. Erika Hamilton2,
  3. Patricia LoRusso3,
  4. Sylvie Rottey4,
  5. Kyriakos P Papadopoulos5,
  6. Shivaani Kummar6,
  7. Nuria Kotecki7,
  8. Fiona C Thistlethwaite8,
  9. Yvan LeBruchec9,
  10. Jerzy Dyczkowski9,
  11. Josef Rüschoff10,
  12. Sara Samari11,
  13. Marie Toukam12,
  14. Joseph Boni12,
  15. Karin Havenith11,
  16. Serafino Pantano9 and
  17. Igor Puzanov13
  1. 1Stanford University School of Medicine, Palo Alto, CA, USA
  2. 2Sarah Cannon Research Institute, Nashville, TN, USA
  3. 3Yale University, New Haven, CT, USA
  4. 4Universitair Ziekenhuis Gent, Gent, Belgium
  5. 5START San Antonio, San Antonio, TX, USA
  6. 6Oregon Health and Sciences University, Portland, OR, USA
  7. 7Institut Jules Bordet, Brussels, Belgium
  8. 8The Christie NHS Foundation Trust and University of Manchester, Manchester, UK
  9. 9ADC Therapeutics SA, Épalinges, Switzerland
  10. 10Targos – A Discovery Life Sciences Company, Kassel, Germany
  11. 11ADC Therapeutics (UK) Ltd, London, UK
  12. 12ADC Therapeutics America, Inc, Murray Hill, NJ, USA
  13. 13Roswell Park Comprehensive Cancer Center, Buffalo, NY, 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 Camidanlumab tesirine (Cami) is an anti-CD25 antibody conjugated to a pyrrolobenzodiazepine dimer cytotoxin designed to deplete CD25+ regulatory T cells (Tregs), thereby increasing the CD8+ cytotoxic T-lymphocyte (CTL):Treg intratumoral balance. Here, we report clinical and biomarker data from a phase 1 clinical trial of Cami as monotherapy and in combination with pembrolizumab (NCT03621982).

Methods The primary objective was to characterize the safety and tolerability of monotherapy and combination therapy in patients (pts) aged ≥18 years with select advanced solid tumors who had exhausted standard of care therapy. Secondary and exploratory objectives included evaluation of preliminary antitumor activity, pharmacokinetics, biomarkers, and immunogenicity. Monotherapy and combination dose escalation both utilized a 3+3 design. As monotherapy, pts received Cami every 3 weeks (Q3W) at escalating dose levels. In combination, pts received pembrolizumab 200mg Q3W every cycle and Cami Q3W for 2 out of every 4 cycles (2 cycles with Cami, followed by 2 cycles without) at escalating dose levels.

Results As of 22 December 2022, 44 patients were treated with Cami monotherapy at doses from 20ug/kg to 150ug/kg. No dose limiting toxicities (DLTs) were reported and the maximum tolerated dose (MTD) was not reached. The most common AEs ≥grade 3, regardless of relationship, were anemia (9.1%), abdominal pain, pulmonary embolism, and rash (6.8% each). Stable disease (SD) was observed in 25% of patients. Thirty-four patients were treated with the combination at doses from 30ug/kg to 100ug/kg. Two DLTs were reported: 1 pneumonitis grade 3 and 1 pancreatitis grade 3. The MTD was not established. The most common AEs ≥grade 3, regardless of relationship, were maculo-papular rash (17.6%), anemia (14.7%), hyponatremia, and decreased lymphocyte count (11.8% each). The disease control rate (1 CR + 4 PR + 10 SD) for the combination cohort was 45.5%. All five responses, along with 3 SDs, were observed among the 18 heavily pretreated patients with ovarian cancer (median prior line of therapy=4; ORR 28%, disease control rate 44%). CTL:Treg balance was altered consistent with the expected mechanism of action of Cami. Biomarkers data in circulation and tumor microenvironment will be reported and correlated with efficacy data.

Conclusions Cami is well-tolerated as monotherapy with no major safety signals. The combination of Cami with pembrolizumab is associated with an increase rate of skin and immune-related AEs. The combination shows encouraging results in heavily pre-treated ovarian cancer pts.

Acknowledgements The authors thank the patients who participated in the study and their family members as well as the investigators and staff who conducted the study. The authors would like also to thank Delphine Yamadjako and Tim Kopotsha, both of ADC Therapeutics for the study and biological samples management.

Trial Registration IND: 139357

EudraCT Number: 2019-003132-23

Ethics Approval All trial investigators received approval from their respective institutional review boards or independent ethics committees. The trial was conducted according to Good Clinical Practice guidelines, per the International Conference on Harmonisation. All patients provided written informed consent before participation.

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.