Asco GI – German Merck pushes on with next immunotherapy

If Merck KGaA was one of the last out of the PD-1/L1 gates when it launched Bavencio in partnership with Pfizer, it seems to be getting a head start on the next evolution of checkpoint inhibition. The German group’s bifunctional oncology asset M7824 has delivered competitive data in late-line gastric cancer – data that offer a glimpse of how effective a dual approach might be in other tumour types.

The speciality-within-a-speciality meeting will also see data from Exelixis, Macrogenics and Array Biopharma as the sector tries to improve on older GI cancer agents like Avastin and newer entrants like Keytruda. Many GI indications as yet are untouched by immuno-oncology, so Merck’s progress in this area makes for interesting reading.

First of 14

Taking the basket trial approach that has seen quick development of PD-1/L1 agents like Keytruda and Opdivo, Merck now has its first data from a study of M7824. In 31 Asian patients with advanced gastric and gastroesophageal adenocarcinoma who had been treated with three or more lines of therapy, M7824, a bifunctional fusion protein that combines a PD-L1 antibody with a TGF-beta receptor II trap, scored a confirmed 19.4% objective response rate.

Bernstein analyst Wimal Kapadia wrote that the data look at least competitive with trials of other PD-1 agents in this disease, such as Opdivo and Keytruda in third-line treatment, which scored objective response rates of 12% and 16% respectively.

Luciano Rossetti, Merck’s global head of biopharma R&D, said the gastric cancer cohort is one of 14 being advanced based on efficacy signals seen in the dose-escalation trials of M7824. An intriguing future dataset that could emerge in time for the main Asco meeting in June is that from non-small cell lung cancer patients who have not been treated with a PD-1/L1 agent.

“Throughout 2018 and early ’19 we’ll be seeing reports on all of these cohorts,” Mr Rossetti said.

A second set of results to be presented at Asco-GI, in third line or later colorectal cancer, looked less impressive, with one partial response and one stable disease among 32 patients recruited at the data cutoff in mid-June. The one patient showing response had a microsatellite-stable tumour and was positive for both KRAS mutation and 20% PD-L1 expression, pointing to potential areas for development. Updated data from this group is set to be presented on Saturday.

And the rest

Meanwhile, Exelixis released data on both of its marketed products, Cabometyx and Cotellic. Data from the second-line hepatocellular carcinoma study of Cabometyx, Celestial, showed it looking like Bayer’s competing Stivarga with an overall survival of 10.2 months and a hazard ratio of 0.76 vs placebo (Exelixis’s Celestial orbit from investment black hole to oncology star, October 16, 2017). 

A combination of Cotellic and Tecentriq in heavily pretreated colorectal cancer patients managed to generate a partial response in seven of 84 patients treated as of May, including three of 29 patients with microsatellite stable and one of eight with low microsatellite instability disease.

Array’s data from the safety lead-in to its phase III colorectal cancer trial of encorafenib and binimetinib showed that 12 of 30 patients responded, one with a complete response. Macrogenics presented data from its trial of margetuximab and Keytruda in gastric and gastroesophageal cancer. In gastric cancer, an overall response rate of 32% was achieved.

Daiichi Sankyo is also had data in a similar setting as Macrogenics, HER-positive gastric cancer. In patients previously treated with Herceptin, DS-8201 achieved a response in 20 of 44 patients and showed a median progression free survival of 5.8 months.

Asco-GI remains a way to gain attention for incremental data ahead of the furore of the main meeting in June. Merck has whet some appetites for what its new immuno-oncology project can achieve, but others working in this space should not be ignored.

To contact the writer of this story email Jonathan Gardner in Virginia at [email protected] or follow @ByJonGardner on Twitter