Updated results have been released from the Phase 3 CheckMate -214 study evaluating the combination of nivolumab plus ipilimumab versus sunitinib in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC).

With a minimum follow-up of 42 months, the combination of nivolumab plus ipilimumab continued to yield superior overall survival (OS), objective response rates (ORR), duration of response (DOR) and complete response (CR) rates for intermediate/poor-risk (IP) patients compared to patients treated with sunitinib alone.

The data was featured in an oral presentation on Saturday, February 15, 2020 at the American Society of Clinical Oncology 2020 Genitourinary Cancers Symposium in San Francisco.

“These clinically meaningful results continue to demonstrate the potential of nivolumab plus ipilimumab to improve the long-term survival of intermediate/poor risk renal cell carcinoma patients,” said Professor Thomas Powles, Director of Barts Cancer Centre.

“These patients suffer from significant unmet need and these results provide the clinical community with a further step in the right direction”.

A significant OS benefit was observed in IP patients treated with nivolumab plus ipilimumab compared to those treated with sunitinib alone.

Per independent review, superior ORR of 42% and CR of 10% (n=425) were observed in IP patients treated with nivolumab plus ipilimumab compared to sunitinib alone (26% and 1% respectively [n=422]).

In the population included in the primary analysis – the IP patients – those treated with nivolumab plus ipilimumab demonstrated significantly improved:

• OS: At 42-months, the OS rate was 52% for patients treated with nivolumab plus ipilimumab versus 39% for patients treated with sunitinib alone [HR 0.66 (95% CI: 0.55-0.80); p<0.0001]

1. ORR: Per independent review, ORR was 42% with nivolumab plus ipilimumab versus 26% for sunitinib alone (p<0.0001):
2. DOR: Median DOR was not reached for patients treated with nivolumab plus ipilimumab and was 19.7 months (95% CI: 16.4-26.4) for patients treated with sunitinib

• CR: Per independent review, 10% of patients treated with nivolumab plus ipilimumab experienced a CR versus 1% with sunitinib alone
• Progression-free survival (PFS): Per independent review, PFS was 35% with nivolumab plus ipilimumab and was 19% for sunitinib alone (PFS at the initial 17.5 months analysis did not meet statistical significance)

Safety analysis showed that no new drug-related deaths occurred in the IP patient arm.

Results were similar for the population included in the secondary analysis – intent-to-treat patients (ITT). Those treated with nivolumab plus ipilimumab compared to sunitinib alone (n=550 and n=546 respectively) demonstrated significantly improved:

• OS: At 42-months, the OS rate was 56% for patients treated with nivolumab plus ipilimumab versus 47% for patients treated with sunitinib alone [HR 0.72 (95% CI: 0.61-0.86); p=0.0002]
• ORR: Per independent review, ORR was 39% with nivolumab plus ipilimumab versus 33% for sunitinib alone (p=0.02)

1. DOR: Median DOR was not reached for patients treated with nivolumab plus ipilimumab and was 24.8 months (95% CI: 19.4-27.3) for patients treated with sunitinib
2. CR: Per independent review, 11% of patients treated with nivolumab plus ipilimumab experienced a CR versus 2% with sunitinib alone

• PFS: Per independent review, PFS was 34% with nivolumab plus ipilimumab and was 22% for sunitinib alone

Safety analysis showed that no new drug-related deaths occurred in the ITT patient arm.

In the UK, nivolumab is licensed in combination with ipilimumab as a first-line treatment for adult patients with intermediate- and poor-prognostic risk advanced RCC only.

The incidence of any grade 3-4 treatment-related adverse events (AE) was consistent with previous reports.

Incidence of treatment-related AEs, treated-related selected AEs and corticosteroid use declined over time and no new safety signals or drug-related deaths occurred with extended follow-up.

“We are encouraged by the results of CheckMate -214, which showcase the potential positive, long-term effect of treating intermediate/poor risk RCC patients with nivolumab plus ipilimumab,” said Faisal Mehmud, UK Country Medical Director, Bristol-Myers Squibb.

“Since the beginning of our nivolumab clinical development programme, we have aimed to improve treatment expectations for patients and, with these results, we are continuing to meet that ambition.” 

RCC is the seventh most common cancer in the UK.

There are ~12,900 new RCC cases in the UK every year, equating to 35 newly diagnosed patients every day.

Approximately 5% of those diagnosed with Stage 4 RCC survive for five years or more following diagnosis.

It is estimated that one in 52 men and one in 87 women will be diagnosed with kidney cancer during their lifetime.

Source: Bristol Myers Squibb