e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

A phase 3, randomized, open-label study (CONTACT-02) of cabozantinib + atezolizumab versus second novel hormonal therapy (NHT) in patients with metastatic castration-resistant prostate cancer (mCRPC) (#397)

Arun Azad 1 , Neeraj Agarwal 2 , Joan Carles 3 , Simon Chowdhury 4 , Bradley McGregor 5 , Axel Merseburger 6 , Stephane Oudard 7 , Fred Saad 8 , Andrey Soares 9 , Yannick Kerloeguen 10 , Fawzi Benzaghou 11 , Ashok Panneerselvam 12 , Nehal Mohamed 12 , Fong Wang 12 , Sumanta Pal 13
  1. Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia
  2. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States
  3. Vall d’Hebron Institut d’Oncología. Hospital Universitari Vall d’Hebron, Barcelona, Spain
  4. Guy’s, King’s and St. Thomas’ Hospitals and Sarah Cannon Research Institute, London, United Kingdom
  5. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
  6. University Hospital Schleswig-Holstein, Lübeck, Germany
  7. European Georges Pompidou Hospital, Paris, France
  8. University of Montreal Hospital Center, Montreal, QC, Canada
  9. Hospital Israelita Albert Einstein, São Paulo, Brazil
  10. F. Hoffmann-La Roche Ltd, Basel, Switzerland
  11. Ipsen Pharma, Boulogne-Billancourt, France
  12. Exelixis, Inc., Alameda, CA, United states
  13. City of Hope Comprehensive Cancer Center, Duarte, CA, United States

Aims: Cabozantinib inhibits multiple tyrosine kinases, including MET, VEGFR, RET, and TAM kinases (Tyro3, AXL, MER), which are involved in tumor pathogenesis and associated with the aggressiveness of prostate cancer. Cabozantinib also promotes an immune-permissive tumor microenvironment and may enhance response to immune checkpoint inhibitors. Cabozantinib in combination with the PD-L1 inhibitor, atezolizumab, has demonstrated clinical activity in mCRPC (Agarwal ASCO 2020; Abstract 5564). We present the design of a phase 3 trial of cabozantinib + atezolizumab vs a second NHT in mCRPC.

 

Methods: This randomized, open-label phase 3 study (NCT04446117) evaluates the efficacy and safety of cabozantinib + atezolizumab versus a second NHT (abiraterone or enzalutamide) in patients with mCRPC who received a prior NHT for locally advanced or metastatic castration-sensitive prostate cancer (mCSPC), non-metastatic (M0) CRPC, or mCRPC. Other eligibility criteria include measurable visceral disease or extrapelvic adenopathy per RECIST v1.1, biochemical or radiological progression on first NHT and good ECOG score (≤1). Exclusion criteria include previous non-hormonal therapy for mCRPC. Prior treatment with docetaxel for locally advanced or mCSPC is allowed.  Patients (N = 580) will be randomized 1:1 to cabozantinib (40 mg PO QD) + atezolizumab (1200 mg IV Q3W) versus abiraterone (1000 mg PO QD) + prednisone (5 mg PO BID) or enzalutamide (160 mg PO QD). Designated and prior NHT must differ. Randomization is stratified by liver metastases, prior docetaxel treatment for locally advanced or mCSPC, and disease state during first NHT. Treatment will continue until lack of clinical benefit, unacceptable toxicity, or withdrawal of consent. The primary endpoints are progression-free survival per RECIST v1.1 by blinded independent radiology committee (BIRC) and overall survival. Additional endpoints include objective response rate per RECIST v1.1 by BIRC, safety and quality of life. Enrollment is ongoing.

 

Clinical Trial Registry Number: NCT04446117