New data from pivotal Phase III CheckMate -9ER trial of Cabometyx® in combination with Opdivo® showed significantly improved QoL benefits and sustained superior efficacy versus sunitinib in patients living with aRCC

• With a median follow-up of two years, Cabometyx® in combination with Opdivo® continues to demonstrate superior progression-free survival, overall survival and objective response rate compared to sunitinib1
• Patients treated with Cabometyx® in combination with Opdivo® report significantly improved health-related quality of life outcomes versus sunitinb in a separate analysis from CheckMate -9ER2

• The expanding evidence base for Cabometyx® is also highlighted in a comparative, retrospective real-world evidence study suggesting that Cabometyx® is associated with a significantly higher response rate and a lower discontinuation rate versus other tyrosine kinase inhibitors (TKIs) after treatment with checkpoint inhibitors (CPI)3

PARIS, FRANCE, 8 February 2021 – Ipsen (Euronext: IPN; ADR: IPSEY) today announced the first presentation of new analyses from the pivotal Phase III CheckMate -9ER trial demonstrating clinically meaningful, sustained efficacy benefits as well as quality of life improvements with the combination of Cabometyx® (cabozantinib) and Opdivo® (nivolumab) compared to sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC).1 These data will be presented in two posters at the virtual American Society of Clinical Oncology 2021 Genitourinary Cancers Symposium (ASCO GU) from 11 – 13 February 2021 and featured in the Poster Highlights Session on 13 February 2021 from 9:00 a.m. – 9:45 a.m. EDT.4

In a new analysis from the CheckMate -9ER trial (Abstract #308) with a median follow-up of two years (23.5 months), Cabometyx® in combination with Opdivo® continued to show superior progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) versus sunitinib, with a low rate of treatment-related adverse events (TRAEs) leading to discontinuation.1 No new safety signals were identified with extended follow-up. Across the full study population, the combination doubled median PFS (17.0 months vs. 8.3 months, respectively; HR 0.52; 95% CI: 0.43 to 0.64), the trial’s primary endpoint, compared to sunitinib. The ORR indicated that nearly twice as many patients responded to Cabometyx® in combination with Opdivo® vs. sunitinib (54.8% vs. 28.4) and the combination maintained improvements in OS, demonstrating a 34% reduction in the risk of death compared to sunitinib (HR: 0.66; 95% CI: 0.50 to 0.87). In an exploratory analysis, the combination was associated with a disease control rate (including complete response, partial response and stable disease) of 88.2% vs. 69.9% with sunitinib and a complete response rate of 9.3% compared to 4.3% with sunitinib. Among patients treated with Cabometyx® in combination with Opdivo®, 6.6% discontinued both agents due to TRAEs, 9.7% discontinued Opdivo® only and 7.2% discontinued Cabometyx® only.1

In an exploratory subgroup analysis of 75 patients with sarcomatoid features, the combination of Cabometyx® with Opdivo® showed benefit in this population typically associated with a poor prognosis, reducing the risk of death by 64% vs. sunitinib (HR 0.36; 95% CI: 0.17 to 0.79) and demonstrating both superior PFS (10.3 months vs. 4.2 months) and ORR (55.9% vs. 22.0%).1

“There is a continued need for new therapies that show benefit across subgroups of patients with advanced renal cell carcinoma,” said Robert Motzer, M.D., Kidney Cancer Section Head, Genitourinary Oncology Service, and Jack and Dorothy Byrne Chair in Clinical Oncology, Memorial Sloan Kettering Cancer Center. “In CheckMate -9ER, nivolumab in combination with cabozantinib doubled progression-free survival, increased overall survival and response rate and, in an exploratory analysis, showed impressive disease control, and these promising efficacy results were sustained with extended follow-up. Also, of note, patients in this study reported significant quality of life improvements, which are important for patients undergoing treatment for this challenging disease”

In a second analysis from the CheckMate -9ER trial (Abstract #285) conducted with 18.1 months of median follow-up, patients treated with the combination of Cabometyx® and Opdivo® reported statistically significant health-related quality of life (HRQoL) benefits.2 Treatment with Cabometyx® in combination with Opdivo® was associated with a lower treatment burden, decreased the risk of confirmed deterioration in HRQoL and a reduction of disease-related symptoms compared to sunitinib. These exploratory outcomes were measured using Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), a quality of life tool specific to kidney cancer, and EQ-5D-3L instruments.2

“As the advances in treatments for kidney cancer transform outcomes for patients, the goals of therapy have expanded from increasing survival to improving quality of life,” said Dr. Cristina Suárez, Medical Oncologist at the Vall d´Hebron University Hospital, Barcelona, Spain and a lead investigator on the Phase III CheckMate -9ER trial. “The additional analyses presented at ASCO GU mean that physicians treating people living with advanced renal cell carcinoma can consider this combination at diagnosis as a first-line option to improve patient outcomes and significantly reduce the risk of deterioration in health-related quality of life scores for their patients. This, in addition to the extended follow-up outcomes data including patients with sarcomatoid features, point to this combination becoming an important treatment approach.”

Cabometyx® in combination with Opdivo® is under review with health authorities globally following the combination’s approval for the first-line treatment of advanced RCC by the U.S. Food and Drug Administration (FDA) in January 2021.

“We’re pleased to share these positive results at ASCO GU, building on the growing body of data for the use of Cabometyx® in first- and second-line settings. These data further support the importance of research investigating outcomes which really matter to patients,” said Prof. Dr. Steven Hildemann, Executive Vice President, Chief Medical Officer, Head of Global Medical Affairs and Patient Safety, Ipsen. “The validations of the type II variation applications to the European Medicines Agency (EMA) for Cabometyx® in combination with Opdivo® last year brought this new combination regimen one step closer to the previously untreated kidney cancer patient population. Despite recent advances, these patients remain in need of more therapeutic options that extend survival and improve quality of life.”

A further notable presentation at ASCO GU evaluated the use of Cabometyx® versus other TKIs after CPI treatment in the real-world management of patients with metastatic renal cell carcinoma (mRCC) (Abstract #293).3

A retrospective observational cohort study evaluating outcomes associated with Cabometyx® or other TKIs (axitinib, lenvatinib, pazopanib, sorafenib, sunitinib) in patients with mRCC following CPI treatment3

Findings from the study suggest that Cabometyx® is an effective and well tolerated option, associated with a significantly higher response rate and a lower discontinuation rate versus other TKIs included in the study, after treatment with CPIs.3

Follow Ipsen on Twitter via @IpsenGroup and keep up to date with ASCO GU Symposium news and updates by using the hashtag #GU21.
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1. Motzer etal., ASCO-GU 2021. Nivolumab + cabozantinib (NIVO+CABO) vs sunitinib (SUN) as first-line therapy for advanced renal cell carcinoma (aRCC): extended follow-up and outcomes in the sarcomatoid subgroup of CheckMate -9ER.
2. Marteau et al., ASCO-GU 2021.Cabozantinib versus other TKIs after CPI treatment in the real-world management of patients with mRCC.
3. Marteau et al., ASCO-GU 2021.Cabozantinib versus other TKIs after CPI treatment in the real-world management of patients with mRCC
4. ASCO Meetings. Attend | Genitourinary Cancers Symposium. Last accessed: February Available from: https://meetings.asco.org/gu/attend.
5. Kidney Cancer Factsheet. GLOBOCAN 2018. Last accessed: February 2021. Available from: https://gco.iarc.fr/today/data/factsheets/cancers/29-Kidney-fact-sheet.pdf.
6. Kidney Cancer. Mayo Clinic. Last accessed: February 2021. Available from: https://www.mayoclinic.org/diseases-conditions/kidney-cancer/symptoms-causes/syc-20352664.
7. Infographic: Kidney Cancer. Mayo Clinic. Last accessed: February 2021. Available from: https://www.mayoclinic.org/diseases-conditions/kidney-cancer/multimedia/kidney-cancer-infographic/ifg-20441505.
8. Survival rates for kidney cancer. American Cancer Society. Last accessed: February 2021. Available from: https://www.cancer.org/cancer/kidney-cancer/detection-diagnosis-staging/survival-rates.html.
9. Orlin, I et al. Renal cell carcinomas epidemiology in the era of widespread imaging. Journal of Clinical Oncology. 2019; 37:15. DOI: https://doi.org/10.1200/JCO.2019.37.15_suppl.e1308.

Attachment

• Ipsen-ASCO-GU-2021-8-February-2021