News Release 

New first-line treatment option for metastatic kidney cancer

Data from latest research presented at the ESMO Virtual Congress 2020

European Society for Medical Oncology

Research News

Lugano, Switzerland, 19 September 2020 - The results of the phase 3 CheckMate 9ER trial have provided a new first-line treatment option for patients with metastatic kidney cancer. The late breaking results are presented at ESMO 2020. (1)

The trial took two drugs used as monotherapies in the second line, nivolumab and cabozantinib, and combined them for use as a first-line treatment against standard of care, sunitinib. The combination was superior to sunitinib for progression-free survival, overall survival, and response rate. There was a consistent benefit of the combination over sunitinib in numerous subgroups including age, sex, PD-L1 expression, bone metastases, International Metastatic RCC Database Consortium (IMDC) risk group, and region of the world.

More than 50% of patients in the combination arm needed a dose reduction of cabozantinib due to adverse events. But only 3% had to stop both drugs because of toxicity compared to 9% of patients in the sunitinib arm. The overall rate of serious adverse events was similar between arms, but liver toxicity was more common in the combination arm. As for immune-related side-effects, 19% of patients in the experimental arm needed corticosteroids; just 4% needed corticosteroids for 30 days or longer.

The findings add to mounting evidence showing the advantages of combination therapy over single drugs. Similar to the CheckMate 9ER trial, the KEYNOTE-426 and JAVELIN Renal 101 trials (2,3) combined an immune checkpoint inhibitor with an anti-angiogenic drug, whereas CheckMate 214 combined two immune checkpoint inhibitors. (4)

Study author Dr Toni K. Choueiri, Director, The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and The Jerome and Nancy Kohlberg Chair and Professor of Medicine, Harvard Medical School, Boston, US said: "The results with combination therapy were statistically significant and clinically meaningful. The risk of progression or death was cut by almost 50%, death was cut by 40%, and the response rate doubled. This will become an important treatment option to choose from. The various combination treatments will unlikely be compared head-to-head, but I think quality of life could differentiate this new therapy, as there was a statistical significance favouring the combination arm with both questionnaires we used. (5) Another factor to consider is that clinicians are familiar with both of these drugs."

Commenting on the findings, Dr Dominik Berthold, Head, Specialised Consultation for Urological Cancers Medical Oncology Service, Department of Oncology, Lausanne University Hospital, Switzerland said: "CheckMate 9ER met its efficacy endpoints and the combination can be considered a new first-line treatment option. However, the medical community is divided about whether two immunotherapies or immunotherapy plus an anti-angiogenic drug is the better choice, since the different combinations appear to have similar effectiveness."

He said longer-term data are needed for CheckMate 9ER: "The 18 months of follow-up is still quite short. The question is whether the responses to treatment are durable or patients progress at some point."

"It would also be useful to learn whether the combination of cabozantinib and nivolumab is effective in non-clear cell carcinoma," added Berthold. "This is a minority of patients with advanced kidney cancer which are not well studied and were excluded from this trial."

Berthold noted that when using drugs with specific mechanisms of action, the first-line treatment choice will also determine the selection of second-line therapy. He explained: "If you start with a combination of immune therapy only, it becomes an automatic choice to use an anti-angiogenic drug in the second line. But if you begin with a combination of two mechanisms of action, such as immune therapy and an anti-angiogenic drug, then the second-line choice is less clear. More data are needed on the most suitable order of therapy for the entire population as well as specific groups such as high tumour burden versus slow-growing disease."

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Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO Virtual Congress 2020

Official Congress Hashtag: #ESMO20

Disclaimer

This press release contains information provided by the author of the highlighted abstract and reflects the content of this abstract. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.

References

(1) Abstract 696O_PR 'Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial' will be presented by Toni K. Choueiri during the Presidential Symposium I on Saturday, 19 September, 18:30 - 20:10 CEST. Annals of Oncology, Volume 31 Supplement 4, September 2020

(2) Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380:1116-1127.

(3) Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380:1103-1115.

(4) Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018;378:1277-1290.

(5) Quality of life was assessed using the Functional Assessment for Cancer Therapy - Kidney Symptom Index (FKSI) and the revised FKSI scale (FKSI-19).

About the European Society for Medical Oncology (ESMO)

ESMO is the leading professional organisation for medical oncology. With more than 25,000 members representing oncology professionals from over 160 countries worldwide, ESMO is the society of reference for oncology education and information. ESMO is committed to offer the best care to people with cancer, through fostering integrated cancer care, supporting oncologists in their professional development, and advocating for sustainable cancer care worldwide. http://www.esmo.org

696O_PR- Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial

T.K. Choueiri1, T. Powles2, M. Burotto3, M.T. Bourlon4, B. Zurawski5, V.M. Oyervides Juarez6, J.J. Hsieh7, U. Basso8, A.Y. Shah9, C. Suarez10, A. Hamzaj11, C.H. Barrios12, M. Richardet13, D. Pook14, Y. Tomita15, B. Escudier16, J. Zhang17, B. Simsek18, A.B. Apolo19, R.J. Motzer20

1Department of Medical Oncology, Dana-Farber Cancer Institute, The Lank Center for Genitourinary Oncology, Boston, MA, USA, 2Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London, UK, 3Department of Medical Oncology, Bradford Hill Clinical Research Center, Santiago, Chile, 4Department of Hemato-Oncology, Urologic Oncology Clinic, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico, 5Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Centre, Bydgoszcz, Poland, 6Department of Medical Oncology, Centro Universitario contra el Cancer Hospital Universitario "Dr. Jose Eleuterio Gonzalez" Universidad Autonoma de Nuevo Leon, Nuevo Leon, Mexico, 7Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA, 8Department of Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy, 9Department of Genitourinary Medical Oncology, M. D. Anderson Cancer Center, Houston, TX, USA, 10Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain, 11Department of Medical Oncology, Ospedale San Donato, Istituto Toscano Tumori, Arezzo, Italy, 12Oncology Research Center, Hospital Sao Lucas, PUCRS, Porto Alegre, Brazil, 13Fundacion Richardet Longo, Instituto Oncologico de Cordoba, Cordoba, Argentina, 14Cabrini Monash University Department of Medical Oncology, Cabrini Health, Malvern, VIC, Australia, 15Departments of Urology and Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan, 16Department of Medical Oncology, Gustave Roussy, Villejuif, France, 17Department of Clinical Research, Bristol Myers Squibb, Princeton, USA, 18Department of Biostatistics, Bristol Myers Squibb, Princeton, NJ, USA, 19Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, 20Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Background: Results from the phase 3 CheckMate 9ER trial evaluating the checkpoint inhibitor (CPI) nivolumab (N) plus the tyrosine kinase inhibitor (TKI) cabozantinib (C) v sunitinib (S) for first-line (1L) treatment of advanced clear cell renal cell carcinoma (aRCC) are reported. As monotherapies, N and C have demonstrated efficacy and a manageable safety profile in aRCC. C has immunomodulatory properties that may counteract tumor-induced immunosuppression, providing a rationale for combining N+C.

Methods: Patients (pts) were randomized 1:1 (stratified by IMDC risk score, tumor PD-L1 expression, region) to N 240 mg flat dose IV Q2W + C 40 mg PO QD v S 50 mg PO for 4 wk (6-wk cycles) until disease progression or unacceptable toxicity (max N treatment, 2 y). Primary endpoint: progression-free survival (PFS; alpha = 0.05 final) by blinded independent central review (BICR). Secondary endpoints (hierarchical testing): overall survival (OS; alpha = 0.011 first interim analysis), objective response rate (ORR; alpha = 0.05 final) by BICR, and safety.

Results: A total of 651 pts (22.6% favorable risk, 57.6% intermediate risk, 19.7% poor risk; 24.9% PD-L1 greater-than or equal to 1%) were randomized to N+C (n = 323) v S (n = 328). With 18.1 mo median (10.6 mo minimum) study follow-up, all 3 efficacy endpoints were met. N+C significantly improved PFS (HR 0.51 [95% CI 0.41-0.64], P < 0.0001; median, 16.6 v 8.3 mo) and OS (HR 0.60 [98.89% CI 0.40-0.89]; P = 0.0010; medians not reached) v S, and results were consistent across prespecified IMDC risk and PD-L1 subgroups. ORR (95% CI) was significantly higher with N+C v S (55.7% [50.1-61.2] v 27.1% [22.4-32.3]; P < 0.0001), and 8.0% v 4.6% of pts achieved complete response. Median duration of response was 20.2 v 11.5 mo for N+C v S. Any-grade TRAEs occurred in 96.6% v 93.1% of pts treated with N+C v S (60.6% v 50.9% grade greater-than or equal to 3). One treatment-related death occurred with N+C v 2 with S. TRAEs led to discontinuation of S in 8.8%, N or C in 15.3%, N+C in 3.1%, N only in 5.6%, and C only in 6.6% of pts.

Conclusions: N+C demonstrated superior PFS, OS, and ORR v S in 1L aRCC. The safety profile of this combination was manageable and consistent with the known single-agent AE profiles of N and C. These results support N+C as a new CPI+TKI option for aRCC pts.

Clinical trial identification: NCT03141177

Editorial acknowledgement: Professional medical writing assistance was provided by Jen Tyson, PhD, of Parexel, funded by Bristol-Myers Squibb Company

Legal entity responsible for the study: Bristol-Myers Squibb Company

Funding: Bristol-Myers Squibb Company (Princeton, NJ), ONO Pharmaceutical Company Ltd. (Osaka, Japan), and Exelixis Inc. (Alameda, CA)

Disclosure:T.K. Choueiri: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: BMS; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Exelixis; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Merck; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Astrazeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: GSK; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, manuscript preparation, clinical trials grants: EMD Serono; Shareholder/Stockholder/Stock options: Pionyr; Shareholder/Stockholder/Stock options: Tempest. T. Powles: Honoraria (self), Advisory/Consultancy: AstraZeneca ; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Incyte ; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: Merck/MSD; Honoraria (self), Advisory/Consultancy: Novartis ; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Seattle Genetics ; Research grant/Funding (institution): AstraZeneca ; Research grant/Funding (institution): Roche. M.T. Bourlon: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses, slide reviews: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Janssen .

J.J. Hsieh: Research grant/Funding (self), sponsered clinical trial: BMS; Advisory/Consultancy, Research grant/Funding (self), sponsored clinical trial: Eisai; Research grant/Funding (self), sponsored clinical trial: Calithera; Research grant/Funding (self), Investigator initiated trial and correlate studies: AstraZenika.

U. Basso: Speaker Bureau/Expert testimony, Research grant/Funding (self), carry out activities of the study: BMS. C. Suarez: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas; Honoraria (self), Advisory/Consultancy: Atrazeneca; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Eusa; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Ipsen; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Sanofi-Aventis; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme Corp..

C.H. Barrios: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer-Ingelheim; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genetech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Abbvie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstellasPharma; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Covance; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): PharmMar. D. Pook: Advisory/Consultancy, Commercial Study Finding: BMS; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Research grant/Funding (self): Ipsen. Y. Tomita: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono pharmacetical; Honoraria (self): BMS; Honoraria (self), Research grant/Funding (self): Pfizer; Research grant/Funding (institution): Takeda. B. Escudier: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis ; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb ; Honoraria (self), Advisory/Consultancy: Ipsen; Honoraria (self), Advisory/Consultancy: EUSA Pharma ; Honoraria (self): Roche/Genentech. J. Zhang: Shareholder/Stockholder/Stock options, Full/Part-time employment: BMS. B. Simsek: Shareholder/Stockholder/Stock options, Full/Part-time employment: BMS. R.J. Motzer: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: Incyte; Advisory/Consultancy: Lilly. All other authors have declared no conflicts of interest.

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