Summit joins the global colorectal fight

After some time during which every major player in the PD-(L)1 x VEGF bispecific race scrambled to lock down global pivotal lung cancer trials, attention is shifting to the next front: microsatellite-stable (MSS) colorectal cancer. This area has seen virtually no movement in two decades, and is one where developers believe that these bispecifics could shift the dial. 

BioNTech/Bristol Myers Squibb, Pfizer and Summit had each signalled plans to initiate global studies in metastatic colorectal cancer, but the timeline for Summit’s entry has, until now, remained unclear. A recent clinicaltrials.gov posting has now resolved those questions: the company’s phase 3 Harmoni-GI3 study of ivonescimab has begun enrolling patients. 

Similar designs

The trial will enrol roughly 600 patients and broadly mirrors the pivotal designs that Bristol and Pfizer are set to launch in the coming months with pumitamig and PF-08634404 respectively. 

Harmoni-GI3 will test a chemo combo of ivonescimab, the anti-PD-1 x VEGF bispecific licensed from Akeso, head to head against Avastin plus chemotherapy, in patients with MSS metastatic colorectal cancer and no BRAF V600E mutations. The primary endpoint is PFS, with readout expected around mid-2028. 

Akeso is running its own pivotal trial in China, but this differs in its choice of chemotherapy regimen. That trial, Harmoni-GI6, is based on data from the AK112-06 study that showed an 82% ORR among 22 MSS metastatic colorectal cancer patients treated with ivonescimab plus Folfoxiri. By contrast, Harmoni-GI3 will test the bispecific antibody alongside Folfox. 

During its October earnings call, Summit said the decision on choice of chemo was shaped by “feedback from KOLs and treating physicians” emphasising that Folfox plus Avastin was the preferred regimen for this setting in the US and other Western regions.

The company also added that the AK112-06 study was expanded to include patients receiving Folfox in both the US and China, and those data, alongside a global phase 2 trial evaluating the same regimen, provided the supportive evidence for the design of the phase 3 trial.

With Summit’s pivotal now under way, Pfizer is expected to start its own global phase 3 in December, while Bristol plans to begin its programme in early 2026. The former tests a similar regimen of PF-08634404 but adds OS as a co-primary endpoint, while the latter differs again in choice of chemo being combined with pumitamig and with Avastin.

Global pivotal trials of anti-PD-(L)1 x VEGF bispecifcs in colorectal cancer

Source: OncologyPipeline.