Bristol Myers reveals subcutaneous Opdivo data in kidney cancer as I-O battle heads to new front

Bristol Myers Squibb is offering a detailed look at pivotal data showing that an under-the-skin version of its PD-1 inhibitor Opdivo works as well as the original intravenous formulation in kidney cancer.

As BMS previously announced, the subcutaneous version of Opdivo provided patients with similar drug serum trough concentrations—as well as similar 28-day average serum concentrations—to the original infusion form in a phase 3 trial in those with previously treated kidney cancer.

Jan. 27, investigators presented detailed findings from the study at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium.

The subcutaneous version, which utilizes Halozyme’s recombinant human hyaluronidase technology, matched up to the IV on the trial’s two co-primary endpoints of the CheckMate-67T trial. The geometric mean ratio for the time-averaged concentration measurement was 2.1 and nearly 1.8 for the minimum serum concentration. In both cases, the numbers far exceeded the predetermined statistical significance bar for noninferiority, and they suggested patients had higher exposure to SC Opdivo than they did with IV.

On a key secondary endpoint, the subcutaneous version triggered a response in 24.2% of patients versus 18.2% for those in the IV group. Therefore, noninferiority on overall response rate was also met. In addition, patients who got the subcutaneous version went a median 7.2 months without disease progression, versus 5.7 months for IV.

A BMS spokesperson declined to offer more details about the company’s regulatory progress with the FDA. The company looks forward to discussing the results with regulators to potentially get the subcutaneous version of Opdivo approved “across multiple indications,” BMS' spokesperson said.

In what could be a disadvantage, the patients who took the subcutaneous version were more likely to develop antidrug antibodies than those on the IV formulation. The rates reached 22.8% for subcutaneous patients and 7% for IV patients after treatment, while the baseline (pre-treatment) rates were 5.9% and 4.2%, respectively. 

Antidrug antibodies may cause a decrease in the amount of drug available, potentially causing a decrease in efficacy, although their exact consequences on a PD-1/L1 drug’s antitumor effect remain unclear.

The recent antidrug antibody results were “as expected for subcutaneous route of administration,” the BMS spokesperson said, “and further assessments did not identify apparent clinically meaningful impact on pharmacokinetics, efficacy, or safety.”

The readout comes amid a push by PD-1/L1 drug developers to advance subcutaneous versions of their top offerings. These subcutaneous drugs could not only potentially improve patients’ treatment experience and access, but also extend market exclusivity timelines.

In the current BMS study, subcutaneous Opdivo is given at a fixed dose once every four weeks, whereas the IV drug is dosed at 3mg/kg once every two weeks. The subcutaneous injection reduced the average administration time to less than 5 minutes from nearly 31 minutes by infusion, investigators said.

This dose provides drug exposure that’s lower than the highest tested safe dose of IV Opdivo and “accounts for a range of body weights while mitigating potentially low bioavailability when administered to a broad patient population,” the BMS spokesperson said.

Roche recently hit a delay on the potential launch of subcutaneous Tecentriq, which also relies on Halozyme’s drug delivery technology. In September, when the FDA was originally expected to reach a verdict on the drug's application, Roche said it had decided to update the therapy’s manufacturing processes “in line with the evolved FDA requirements.”

Once those changes are made, Roche expects to receive FDA’s approval this year, the Swiss pharma said at the time.

As for the PD-1 market leader, Merck itself recently shifted gears on a subcutaneous version of Keytruda. Rather than a prior sans hyaluronidase candidate that’s dosed once every three weeks, the New Jersey pharma is now exploring a potentially six-week dosing regimen that’s also co-formulated with a recombinant hyaluronidase enzyme. But clinical data from that formulation could be years out.

Merck is bracing for Keytruda’s patent cliff in 2028, and company executives have pointed to an subcutaneous formulation as one way to soften the blow. As the PD-1 inhibitor is often used by itself in early-stage cancers, a subcutaneous version of Keytruda wouldn't need to worry about another infused combo partner canceling out its convenience edge, Merck’s CEO Rob Davis suggested during a presentation during the annual J.P. Morgan Healthcare Conference earlier this month.

Meanwhile, the world’s first approval for a subcutaneous checkpoint inhibitor already launched in 2021. During that year, a partnership between 3D Medicines, Alphamab and Simcere picked up approval in China for their subcutaneous PD-L1 antibody, envafolimab, in microsatellite instability-high or mismatch repair deficient solid tumors.