Bristol Myers Squibb and Exelixis, Inc. announced four-year follow-up results from the CheckMate -9ER trial evaluating Opdivo® (nivolumab) in combination with CABOMETYX® (cabozantinib) vs. sunitinib in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC). Results continued to show superior progression-free survival (PFS) and objective response rates (ORR) in patients treated with Opdivoplus CABOMETYXover sunitinib, regardless of risk classification based on International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scores.

Superior overall survival (OS) was also observed in patients treated with the combination. These updated results, including data showing health-related quality-of-life benefits with Opdivo in combination with CABOMETYX vs. sunitinib, will be featured in an oral presentation at the American Society of Clinical Oncology (ASCO) 2024 Genitourinary Cancers Symposium from January 25-27, 2024.

At a median follow-up of 55.6 months (48.1 months minimum), all patients randomized to the Opdivo plus CABOMETYX treatment arm (n=323) continued to experience benefits over those who received sunitinib (n=328) across efficacy endpoints: PFS (primary endpoint): PFS continued to favor Opdivo plus CABOMETYX, with median PFS nearly doubled with the combination regimen at 16.4 months vs. 8.4 months with sunitinib (Hazard Ratio [HR] 0.58; 95% Confidence Interval [CI]: 0.49 to 0.70). OS (secondary endpoint): Treatment with Opdivo in combination with CABOMETYX elicited durable survival benefit over sunitinib, with a median OS of 46.5 months compared to 36.0 months with sunitinib (HR 0.77; 95% CI: 0.63 to 0.95).

ORR (secondary endpoint): The combination regimen showed durable response improvements, doubling the ORR compared to sunitinib (55.7% vs. 27.7%, respectively). Complete response (CR): Patients who received Opdivo plus CABOMETYX continued to show CR benefit, with triple the number of patients achieving CR vs.

sunitinib (13.6% vs. 4.6%). Duration of response (DOR): Opdivo plus CABOMETYX was associated with a longer median DOR of 22.0 months vs.

15.2 months in the sunitinib group. Safety: No new safety concerns were identified in this follow-up analysis. Among all treated patients, any-grade treatment-related adverse events (TRAEs) occurred in 97.5% in the Opdivo plus CABOMETYX group compared to 93.1% in the sunitinib group.

Grade =3 TRAEs occurred in 67.5% of Opdivo plus CABOMETYX-treated patients vs. 55.3% in sunitinib-treated patients. Additionally, in exploratory analyses, durable and clinically meaningful benefits were observed in patient subgroups across risk groups, including within the favorable-risk and intermediate- and poor-risk groups: OS: Among patients with intermediate-/poor-risk, median OS was 43.9 months for those treated with Opdivo plus CABOMETYX vs.

29.3 months with sunitinib (HR 0.73; 95% CI: 0.58 to 0.91). In patients with favorable risk, median OS was similar across treatment arms at 52.9 months with the combination regimen and 58.9 months with sunitinib (HR 1.10; 95% CI: 0.69 to 1.75). PFS: PFS was improved with the combination regimen in patients with intermediate-/poor-risk with a median PFS of 15.4 months compared to 7.1 months with sunitinib (HR 0.56; 95% CI: 0.45 to 0.68), as well as in those with favorable risk at 21.4 months vs.

12.8 months (HR 0.69; 95% CI: 0.48 to 1.00). ORR: In patients with intermediate-/poor-risk, ORR was more than doubled at 52.6% with Opdivo and CABOMETYX vs. 23.0% with sunitinib.

In those with favorable risk, ORR was 66.2% vs. 44.4%, respectively. CR: Among those with intermediate-/poor-risk profiles, the number of patients who achieved CR more than tripled (12.9% vs.

3.5%) with the combination regimen compared to sunitinib. In those with favorable risk profiles, the number of patients who achieved CR was doubled (16.2% vs. 8.3%) with the combination regimen.

DOR: Median DOR was also improved with Opdivo and CABOMETYX across both groups. Among the intermediate- and poor-risk group, those treated with the combination regimen had a median DOR of 23.1 months vs. 13.8 months with sunitinib.

Among the favorable risk group, median DOR was 18.7 months vs. 17.8 months, respectively. Bristol Myers Squibb and Exelixis thank the patients and investigators involved in the CheckMate -9ER clinical trial.

CheckMate -9ER is an open-label, randomized, multi-national Phase 3 trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma (RCC). A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1=1%) were randomized to receive Opdivo plus CABOMETYX (n=323) vs. sunitinib (n=328).

The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination vs.

sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co. and co-funded by Exelixis, Inc., Ipsen Pharma SAS and Takeda Pharmaceutical Company Limited.