Corvus goes pivotal in peripheral T-cell lymphoma

There hasn’t been much industry interest in ITK inhibition, but that hasn’t stopped Corvus going all in on this mechanism. Clinicaltrials.gov has just listed a phase 3 study of the group’s lead project, soquelitinib, in peripheral T-cell and other lymphomas.

There are currently few options in PTCL, although promising data from various projects were presented at last year’s ASH meeting, suggesting that things might be changing. Beyond this Corvus reckons soquelitinib could have broader use, including in various autoimmune diseases and solid tumours.

This is because ITK is thought to be involved in both malignant T-cell growth and immune function. Specifically, blocking ITK is said to increase levels of type 1 T-helper cells (Th1) that spur cancer and viral cell eliminations, and reduce levels of Th2 cells involved in autoimmune and inflammatory disorders.

Still, there are no other groups looking at ITK for cancer, according to OncologyPipeline.

Corvus has an early atopic dermatitis trial ongoing, but its big focus for now is lymphoma. The imminent pivotal trial will enrol 150 patients with relapsed/refractory PTCL who have received at least one but no more than three prior therapies.

The study will compare soquelitinib 200mg twice daily against physician’s choice of either Beleodaq or Folotyn, and the primary endpoint is PFS; the trial will also evaluate response rates and overall survival.

Beleodaq looks like a fairly easy comparator to beat, having long been used in PTCL, an aggressive but relatively rare group of cancers, without much success.

PTCL bar

Perhaps the more relevant bar to clear is the 44% ORR seen with both Dizal’s JAK1 inhibitor golidocitinib and Daiichi Sankyo’s EZH1/2 inhibitor valemetostat in late-line PTCL, in global mid-stage studies presented separately at last year’s ASH meeting. Haihe Biopharma’s HH2853 produced an even more impressive 65% ORR, albeit in a smaller phase 1 Chinese trial.

In Corvus’s phase 1 T-cell lymphoma study the ORR was 39% among 23 evaluable patients receiving the optimum 200mg twice-daily dose of soquelitinib, and who had received three or fewer prior therapies. The company will have to hope that this holds up in a more rigorous phase 3.

Golidocitinib and valemetostat were approved for relapsed/refractory PTCL in China and Japan respectively in June; their paths forward in the US are less clear. 

Pfizer’s CD30-targeting ADC Adcetris is also approved for PTCL, but is given first line.

Meanwhile, another would-be contender, Innate Pharma, was forced to abandon PTCL hopes earlier this year following a phase 1 failure, and is now focused on the smaller cutaneous T-cell lymphomas Sézary syndrome and mycosis fungoides. 

Soquelitinib’s varied development

Source: OncologyPipeline & company presentation.