Compass points the way towards its next readout

After Compass Therapeutics last year claimed a pivotal win with tovecimig in second-line biliary tract cancer, an important upcoming readout will determine whether this DLL4 x VEGF-targeting antibody can be filed with regulators.

The data released last year concerned overall response rates, the primary endpoint of the trial in question, Companion-002. But also vital will be the key secondary metrics of progression-free and overall survival, which are due late this quarter.

The phase 2/3 Companion-002 study tests tovecimig plus paclitaxel, versus paclitaxel alone, in biliary tract cancer patients who have previously progressed on gemcitabine and platinum-containing chemotherapy.

Last April the company reported a 17% ORR among 111 patients receiving the combo, compared with 5% for paclitaxel, a result said to have hit statistical significance with a p value of 0.031. At the time, survival data were delayed from the second half until the fourth quarter of 2025, and they were later pushed back further, until the first quarter of 2026.

Compass blamed fewer deaths in the study than initially expected, leading to hopes that tovecimig might be improving survival. However, it’s also possible that all Companion-002 patients – not just those on tovecimig – are living longer than expected owing to certain baseline characteristics. 

Assuming positive survival data, Compass has said it hopes to file the project with regulators later this year. Investors seem optimistic, with the group's share price having almost tripled since the ORR data were reported.

Right comparator?

However, Companion-002 has drawn criticism for using paclitaxel as the comparator, with NCCN guidelines citing Folfox chemo as the preferred second-line regimen.

Indeed, Compass has given survival numbers with Folfox as a benchmark to hit in its quest to make tovecimig the second-line standard of care. In the ABC-06 trial, Folfox led to median PFS of 4.0 months and median OS of 6.2 months.

Toxicity will also be closely watched when the full results are reported. All Compass said in April was that tovecimig’s safety profile in Companion-002 was in line with previous studies, and that full data would be released along with the PFS and OS results.

Compass also has ambitions in first-line biliary tract cancer, where an MD Anderson-sponsored phase 1/2 trial is ongoing, testing tovecimig plus Imfinzi and chemo; results could come this year.

And the company plans to start a solid tumour basket trial this half in DLL4-positive tumours including colorectal, gastric, ovarian, renal and liver.

DLL4 is involved in angiogenesis, but previous attempts to hit it have been limited by adverse events such as pulmonary hypertension and heart failure. It’s hoped that targeting both DLL4 and VEGF could improve potency, although other projects with this dual mechanism appear to have fallen by the wayside, such as AbbVie’s dilpacimab (ABT-165) and Feng Biosciences’ navicixizumab.

Tovecimig’s upcoming readout

Notes: *primary endpoint; **key secondary endpoints. Source: OncologyPipeline.