GSK suffers a setback with its TIM-3 programme

GSK has become the latest drugmaker to run into difficulties in developing a drug targeting the immune checkpoint receptor TIM-3, after its cobolimab candidate flunked a phase 3 trial in lung cancer.

In its second-quarter update this morning, GSK revealed that the COSTAR study of cobolimab in combination with its PD-1 inhibitor Jemperli (dostarlimab) and docetaxel was unable to show any improvement in overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients previously treated with PD-1/PD-L1 inhibitor-based cancer immunotherapies.

COSTAR is comparing Jemperli plus cobolimab and docetaxel chemotherapy to Jemperli/docetaxel and docetaxel alone. In a statement, GSK said advanced NSCLC "remains a challenging treatment setting where novel combinations have yet to improve outcomes for most patients."

The COSTAR readout is another disappointment in attempts to combine PD-1/PD-L1 inhibitors – which only work in around a third of patients – with other checkpoint inhibitors in the hope of broadening and boosting their efficacy.

GSK was also developing a drug called belrestotug targeting TIGIT, another checkpoint, but abandoned it and an alliance with its originator, iTeos, in May. The company revealed in its latest update that it had taken a £471 million ($630 million) charge in the second quarter in connection with that decision.

Last year, Novartis ended the development of its TIM-3 antibody sabatolimab in myelodysplastic syndromes (MDS), a form of blood cancer, after a disappointing readout in a late-stage trial. It had also been in clinical testing for acute myeloid leukaemia (AML).

The lengthening list of discontinued clinical-stage candidates includes Roche's TIM-3/PD-1 inhibitor bispecific antibody RO7121661, two Bristol Myers Squibb's antibody-based drugs developed in partnership with Five Prime, a bispecific from Eli Lilly, and an Incyte antibody.

Cobolimab – which was acquired by GSK when it took over Tesaro in a $5.1 billion deal agreed in 2019 – remains in other clinical trials, including mid-stage combination studies with Jemperli in paediatric tumours and cervical, liver, and skin cancers, according to the clinicaltrials.gov registry.

There has been no word from the company yet on whether it intends to continue its development, and only the NSCLC trial appears in its pipeline listing.

Today, GSK shrugged off the disappointing development as it reported £8 billion in second-quarter sales – a rise of 6% that beat analyst consensus estimates – on the back of strong growth of cancer therapies and other specialty medicines.

Chief executive Emma Walmsley said: "With the breadth of our current business and the growth opportunities we have in our pipeline, we are highly confident in our outlook for sales of more than £40 billion by 2031."

Hitting that target could depend on what happens with another of GSK's cancer drugs, multiple myeloma therapy Blenrep (belantamab mafodotin), which was taken off the market a couple of years ago, but which has been freshly approved in Europe and other markets with stronger data. Its progress has been delayed in the important US market, however, after FDA advisors voted that its risks outweighed its benefits. The US regulator is due to deliver its decision on the drug in October.