CCR8 promise and peril

Two years after CCR8 emerged as one of immuno-oncology's promising targets the field is starting to deliver a clearer, if still mixed, picture. 

One of the latest developments comes from Coherus, which is preparing to launch a new prostate cancer study combining its CCR8-targeting antibody tagmokitug with Johnson & Johnson's KLK2-targeting T-cell engager pasritamig. Several big pharma companies have also quietly ramped up efforts in CCR8, though some others have decided that the approach has no future, including BeOne, which has just terminated a trial of its project, BGB-A3055.

The receptor CCR8 has drawn attention because of its role in tumour-associated immune suppression. The target is predominantly expressed on T regulatory cells, particularly those in the tumour microenvironment, and is thus thought to help cancers evade immune attack. 

Coherus's plan to combine tagmokitug, which it acquired from Surface Oncology in 2023, with pasritamig marks the first time a T-cell engager and an anti-CCR8 will be tested clinically. 

Early data

Still, data backing the approach remain thin. In early trials tagmokitug failed to generate responses as monotherapy, and in combination with PD-1 blockade at the highest dose reported a single partial response in head and neck cancer among the three patients treated in this cohort. 

That lone response hardly proves the concept. But it does reinforce a widely held view in the field: CCR8 antibodies might have the greatest potential in combinations designed to amplify T-cell activity rather than as standalone treatments. Additional data from tagmokitug are expected this year.

So far the strongest single-agent signal has come from Qilu's QLP2117. In December the company reported that in a phase 1 basket trial, the response rate was 33% among nine patients treated at its highest dose. Two of four gastric cancer patients reported partial responses, and one of five with NSCLC. However, there was also a dose-limiting toxicity at this dose, 540mg.

For now, the most advanced programme belongs to LaNova Medicines, which plans to begin a pivotal gastric cancer trial of cafelkibart in April. This comes after LaNova reported a 36% response rate for a combination of cafelkibart with a PD-1 blocker in 36 patients, around half of whom had already progressed after prior anti-PD-1 therapy.

Great expansions

Meanwhile, several big pharma players are expanding their bets. Trial registries show significant enrolment increases for programmes run by Bristol Myers Squibb, AbbVie and Gilead, the last of which licensed its anti-CCR8 antibody from Jounce.

Bristol, the first company to bring a CCR8 MAb into the clinic, has expanded its imzokitug trial from 185 to more than 900 patients, with results expected in 2028.  Gilead's denikitug study has grown from 62 to around 412 planned participants, also targeting a 2028 readout. And AbbVie's programme, ABBV-514, has expanded from 136 to 512 patients, with data expected in 2027. 

Another player expected to report data next year is Roche. The first in-human trial of its anti-CCR8 antibody enzelkitug in combination with Tecentriq is expected to read out in early 2027.

Discontinuations

Still, the sector has also seen attrition. Several companies have quietly stepped away from their CCR8 programmes in recent months, without releasing clinical data.

BeOne just terminated its study of BGB-A3055 after enrolling 99 patients, below the planned 263. The clinicaltrials.gov entry notes that this was a sponsor decision, "and not driven by safety concerns". This development came after the company earlier told ApexOnco that the programme was still under evaluation and had not been discontinued.

Meanwhile, Zai Lab stopped its ZL-1218 trial in October, while Bayer discontinued its antibody lanerkitug in November. Amgen appears to be heading in a similar direction: its AMG 355 trial was recently marked "not recruiting" though enrolment stopped at 77 patients, far short of the 535 originally planned. The company has not responded to questions regarding this asset at the time of publication.

Clinical stage anti-CCR8 antibodies

Note: *CCR8 inhibitor rather than a MAb. Source: OncologyPipeline.