Cabometyx® in combination with nivolumab shows durable survival benefits at over three-years’ follow-up in first-line advanced renal cell carcinoma

• ​​​​​​Three-year data – with a median follow-up of 44 months – from the Phase III CheckMate -9ER trial demonstrate maintained overall survival benefits with Cabometyx plus nivolumab compared to sunitinib regardless of IMDC risk score¹
• Data represent the longest reported follow-up in any Phase III trial with a tyrosine kinase inhibitor- immunotherapy regimen in this population
• CheckMate -9ER data to be presented at ASCO GU alongside six additional abstracts supporting the use of Cabometyx either alone or in combination with immunotherapy in advanced renal cell carcinoma^2,3,4,5,6,7

PARIS, FRANCE, STRICTLY EMBARGOED until 11.00pm CET, 13 February 2023 - Ipsen (Euronext: IPN; ADR: IPSEY) today announced three-year minimum, 44-month median, follow-up results from the Phase III CheckMate -9ER trial showing that Cabometyx^® (cabozantinib) in combination with nivolumab provides survival and response rate benefits after three-years in the first-line treatment of advanced renal cell carcinoma (aRCC), compared to sunitinib.¹ These findings are being presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) from 16–18 February 2023.

RCC is the most common type of kidney cancer, accounting for approximately 90% of cases.⁸ If detected in the early stages, the five-year survival rate is high, but for people living with advanced or late-stage metastatic RCC the survival rate is much lower, at around 12%.⁹

“Despite the progress made through science and medicine, there remains a need for treatment options that can durably extend survival for patients with metastatic renal cell carcinoma, especially for those classified as higher risk,” said Mauricio Burotto, M.D., medical director, Bradford Hill Clinical Research Center, Santiago, Chile.

“With these updated results from CheckMate -9ER, we’ve now seen nivolumab in combination with cabozantinib durably extend survival and sustain response benefits compared to sunitinib for over three years, regardless of patients’ risk classification. These results reinforce the importance of this immunotherapy-tyrosine kinase inhibitor regimen for patients and its potential to help change survival expectations for patients with this challenging cancer.”

In the CheckMate -9ER trial, OS (overall survival) benefits were maintained at over three-years of follow-up.¹  Median OS was significantly higher for patients on Cabometyx in combination with nivolumab versus sunitinib, at 49.5 versus 35.5 months respectively [hazard ratio (HR) 0.70 [95% confidence interval (CI) 0.56–0.87], p=0.0014)], demonstrating a 30% reduction in the risk of death.1 Additionally, median OS improved by 11.8 months since the previous data cut at 32.9 months median follow-up.¹

Patients treated with Cabometyx in combination with nivolumab, versus those on sunitinib, also experienced benefits in terms of progression-free survival (PFS) and objective response rate (ORR; cancer shrinking with treatment):¹

• Median PFS was almost doubled at 16.6 versus 8.4 months for Cabometyx in combination with nivolumab versus sunitinib respectively (HR 0.58 [95% CI 0.48–0.71], p<0.0001).
• ORR was doubled with Cabometyx in combination with nivolumab versus sunitinib (95% CI, 56% [50–61] versus 28% [24–34]). Responses also continued to be more durable with the combination, with a median DoR (duration of response) of 23.1 months compared to 15.2 months with sunitinib.
• Complete Response (CR) more than doubled for patients receiving Cabometyx in combination with nivolumab (12%) compared to those receiving sunitinib (5%).
• The safety profile identified in the CheckMate -9ER trial was consistent with that previously observed.
• Results were also assessed by the following International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores: favorable, intermediate, intermediate/poor and poor. Benefits were seen with Cabometyx in combination with nivolumab across all efficacy measures (OS, PFS, ORR and CR), regardless of IMDC risk.¹  

“At Ipsen, our goal is for people to live longer and live well with cancer and these results reinforce the value Cabometyx can bring to patients with advanced RCC when combined with immunotherapy in the first-line setting,” said Steven Hildemann, M.D. PhD, Executive Vice President, Chief Medical Officer, Head of Global Medical Affairs and Global Patient Safety.

“The results from the CheckMate -9ER study continue to demonstrate sustained, now three-year long-term benefits for people living with advanced renal cell carcinoma across the most meaningful efficacy measures and risk scores, adding to the body of evidence we have for Cabometyx plus nivolumab. We sincerely thank the patients who participated in the trial, their families and their healthcare teams.”

Six additional abstracts will be presented at ASCO GU assessing the benefits of Cabometyx in aRCC and non-clear cell renal cell carcinoma (nccRCC). These include:

• The CaboCombo trial, which is a prospective, international, non-interventional study of first-line Cabometyx plus nivolumab for the treatment of patients with aRCC. This study will gather real-world evidence on the first-line use of Cabometyx plus nivolumab and demonstrates Ipsen’s commitment to advancing the evidence base on treatment options for people living with aRCC.³
• Cohort 10 of the COSMIC-021 trial, which evaluates Cabometyx in combination with atezolizumab in nccRCC, and further assesses Cabometyx’s potential when combined with immune checkpoint inhibitors.⁷
• A biomarker analysis from the CheckMate -9ER trial showing that at 44-month median follow-up, median PFS and OS were improved with Cabometyx plus nivolumab versus sunitinib, regardless of PD-L1 status.⁴

References

1. Burotto, M., et al. Nivolumab plus cabozantinib vs sunitinib for first-line treatment of advanced renal cell carcinoma (aRCC): 3-year follow-up from the phase 3 CheckMate -9ER trial. Presented at ASCO Genitourinary Cancers Symposium; 2023 February 16-18; San Francisco, California.
2. Albiges, L., et al. CaboPoint: Interim results from a phase II study of cabozantinib after checkpoint inhibitor (CPI) therapy in patients with advanced renal cell carcinoma (RCC). Presented at ASCO Genitourinary Cancers Symposium; 2023 February 16-18; San Francisco, California.
3. Barthélémy, P., et al. CaboCombo: a prospective international non-interventional study of first-line cabozantinib plus nivolumab for the treatment of patients with advanced renal cell carcinoma. Presented at ASCO Genitourinary Cancers Symposium; 2023 February 16-18; San Francisco, California.
4. Choueiri, T., et al. Biomarker analysis from the phase III CheckMate -9ER trial of nivolumab + cabozantinib (N+C) v sunitinib (S) for advanced renal cell carcinoma (aRCC). Presented at ASCO Genitourinary Cancers Symposium; 2023 February 16-18; San Francisco, California.
5. Nathan, P., et al. CARINA interim analysis: a non-interventional study of real-world treatment sequencing and outcomes in patients with advanced renal cell carcinoma initiated on first-line checkpoint inhibitor-based combination therapy. Presented at ASCO Genitourinary Cancers Symposium; 2023 February 16-18; San Francisco, California.
6. Vuillemin, A., et al. Study of cabozantinib in second line under real-life setting in patients with advanced renal cell carcinoma (aRCC): study design of a French, retrospective, multicenter study (OCTOPUS). Presented at ASCO Genitourinary Cancers Symposium; 2023 February 16-18; San Francisco, California.
7. McGregor, B., et al. Cabozantinib in combination with atezolizumab in non-clear cell renal cell carcinoma: extended follow-up results of cohort 10 of the COSMIC-021 study. Presented at ASCO Genitourinary Cancers Symposium; 2023 February 16-18; San Francisco, California.
8. Hsieh, J.J., et al. 2017. Renal cell carcinoma. Nature reviews. Disease primers. 3(17009), doi: 10.1038/nrdp.2017.9
9. Padala, S.A., et al. 2020. Epidemiology of Renal Cell Carcinoma. World Journal of Oncology. 11(3) 79-87, doi: 10.14740/wjon1279
10. GLOBOCAN 2020. Kidney Cancer Factsheet. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/29-Kidney-fact-sheet.pdf Last accessed: February 2023.
11. Lalani, A.A., et al. 2022. Evolving landscape of first-line combination therapy in advanced renal cancer: a systematic review. Ther Adv Med Oncol. 14, 1-17, doi: 10.1177/17588359221108685
12. Clinicaltrials.gov. 2022. A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate -9ER). Available at: https://clinicaltrials.gov/ct2/show/NCT03141177?term=NCT03141177&draw=2&rank=1. Last accessed: February 2023.
13. Clinicaltrials.gov. 2022. A Study of the Effectiveness of Cabozantinib in Combination With Nivolumab as First-line Treatment of Advanced Renal Cell Carcinoma (aRCC) in Adults (CaboCombo). Available at: https://clinicaltrials.gov/ct2/show/NCT05361434?term=NCT05361434&draw=2&rank=1. Last accessed: February 2023.
14. Clinicaltrials.gov. 2022. Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors. Available at: https://clinicaltrials.gov/ct2/show/NCT03170960?term=NCT03170960&draw=2&rank=1. Last accessed: February 2023.