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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

5901 - Phase 1b study (COSMIC-021) of cabozantinib in combination with atezolizumab: Results of the dose escalation stage in patients (pts) with treatment-naïve advanced renal cell carcinoma (RCC)

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Presenters

Neeraj Agarwal

Citation

Annals of Oncology (2018) 29 (suppl_8): viii303-viii331. 10.1093/annonc/mdy283

Authors

N. Agarwal1, U. Vaishampayan2, M. Green3, F. di Nucci3, P. Chang4, C. Scheffold4, S. Pal5

Author affiliations

  • 1 Internal Medicine, Huntsman Cancer Institute, 84112 - Salt Lake City/US
  • 2 Oncology, Karmanos Cancer Center, Detroit/US
  • 3 -, Genentech, South San Francisco/US
  • 4 Clinical Science, Exelixis Inc., South San Francisco/US
  • 5 Medical Oncology & Therapeutics Research, City of Hope, Duarte/US
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Resources

Abstract 5901

Background

Cabozantinib (C) is an inhibitor of multiple receptor tyrosine kinases involved in tumor cell proliferation, neovascularization, and immune cell regulation, including MET, VEGFRs, and TAM family of kinases (TYRO3, MER, and AXL). Preclinical/clinical studies suggest that C promotes an immune-permissive environment that may facilitate synergistic effects with checkpoint inhibitors. This Phase 1b study evaluates C in combination with the programmed death ligand (PD-L1) targeting antibody atezolizumab (A) in pts with solid tumors (NCT03170960).

Methods

Safety and clinical activity of C (2 dose levels: 40 mg, 60 mg QD) + A (1200 mg Q3W) administered in 3-week cycles were evaluated in a 3 + 3 dose escalation design. Safety data of all pts and criteria for dose limiting toxicity (DLT) determined the recommended dose (RD) for a subsequent expansion stage. Tumor response was assessed by CT/MRI and bone scan (RECIST v 1.1).

Results

12 pts with treatment-naïve advanced RCC (mostly clear-cell subtype) were treated in the dose escalation stage (6 at each dose level). At data cutoff, all pts were actively receiving study treatment (range, 3–12 cycles). There were no DLTs or serious adverse events (AEs) in either C+A dose cohort. Most AEs were Grade 1/2 including immune-related AEs. Grade 3 AEs included 3 events of hypertension, 2 events each of diarrhea and hypophosphatemia, and 1 pulmonary embolism. There were no Grade 4/5 AEs. Among 10 pts investigator-assessed confirmed ORR was 50% (1 CR, 4 PRs); 2 additional pts had unconfirmed PRs with only 1 tumor assessment at data cut-off.

Conclusions

C+A is well tolerated and shows encouraging anti-tumor activity in advanced RCC. C 40 mg QD + A 1200 mg Q3W was selected as the RD for expansion in multiple solid tumor cohorts including RCC.

Clinical trial identification

NCT03170960.

Legal entity responsible for the study

Exelixis, Inc.

Funding

Exelixis, Inc.

Editorial Acknowledgement

Disclosure

N. Agarwal: Consulting or advisory role: Pfizer, Novartis, Merck, Genentech, Eisai, Exelixis, Clovis, EMD Serono, BMS, AstraZeneca, Astellas. U. Vaishampayan: Honoraria: Astellas Pharma, Bayer, Bristol-Myers Squibb, Exelixis, Genentech, Janssen, Novartis, Pfizer, Sanofi; Consulting or advisory role: Astellas Pharma, Bayer, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Novartis, Pfizer; Speakers' bureau: Astellas Pharma, Bayer, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Novartis, Pfizer, Sanofi; Research funding: Astellas Pharma, Bristol-Myers Squibb, Exelixis, Novartis, Pfizer. M. Green, F. di Nucci: Employee: Genentech. P-Y. Chang: Employee of Exelixis Inc. C. Scheffold: Employee of and owns stock in Exelixis, Inc. S. Pal: Honoraria: Astellas Pharma, Medivation, Novartis; Consulting or advisory role: Aveo, Bristol-Myers Squibb, Exelixis, Genentech, Myriad Pharmaceuticals, Novartis, Pfizer; Research funding: Medivation.

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