BMS' plan to move Opdivo into adjuvant RCC gets knocked back

Bristol-Myers Squibb has revealed that its checkpoint inhibitor combination of Opdivo and Yervoy failed a phase 3 trial as adjuvant (post-surgery) therapy for renal cell carcinoma (RCC), the most common form of kidney cancer.

The disappointing outcome from the CheckMate -914 trial undermines BMS' hopes of moving PD-1 inhibitor Opdivo (nivolumab) and CTLA4 inhibitor Yervoy (ipilimumab) treatment into earlier-stage cancers.

Opdivo/Yervoy has been approved since 2018 as first-line treatment for patients with intermediate- and poor-risk advanced RCC, and BMS was hoping to extend the use of the regimen into patients with localised RCC tumours that are treatable with surgery.

The new data come from Part A of the CheckMate -914 trial, which involved patients with localised RCC who had full or partial kidney removal surgery and were considered at moderate or high risk of the cancer coming back.

The results showed that Opdivo/Yervoy was no better than placebo at improving disease-free survival, said BMS. Part B of the trial is investigating Opdivo alone versus placebo in this setting and will continue to read out, although now looks likely to disappoint.

It's a blow to BMS' particularly as its arch-rival in the PD-1 inhibitor category – Merck & Co – recently scored approval for its drug Keytruda (pembrolizumab) as adjuvant RCC.

"Even with notable progress in the treatment of metastatic renal cell carcinoma, there are still limited treatment options available for patients with localised disease," said BMS' Dana Walker, who heads up the drugmaker's genitourinary cancer development programmes.

She noted that Opdivo and Opdivo/Yervoy have previously been shown in trials to be effective as adjuvant therapy for other cancers, including genitourinary tumours.

That includes bladder cancer for example, where Opdivo was approved last year for use after surgery in patients with muscle-invasive urothelial carcinoma (UC), as well as for oesophageal/gastro-oesophageal cancer and melanoma.

Securing approvals in the adjuvant or neo-adjuvant (pre-surgery) setting is a key strategy for BMS and other checkpoint inhibitor developers, as it allows them to position their drugs as the earliest cancer immunotherapy option in the treatment pathway.

Opdivo and Opdivo/Yervoy have also shown a benefit in clinical trials alongside Exelixis' tyrosine kinase inhibitor Cabometyx (cabozantinib) as first-line therapy in advanced RCC, while Opdivo proved to be effective as second-line treatment.

BMS said it is also investigating Opdivo and Opdivo plus Yervoy in combination with novel agents targeting alternative immunomodulatory molecules and pathways in RCC.

Meanwhile, other pharma companies are also developing checkpoint inhibitors for adjuvant RCC, including Roche whose Tecentriq (atezolizumab) is in the phase 3 IMmotion010 study, and AstraZeneca which is testing its Imfinzi (durvalumab) alone and in combination with CTLA4 drug tremelimumab in the RAMPART trial.