More bad news for TIGIT as MSD stops another trial
Another TIGIT trial failure has been abandoned, casting a shadow once again over the target as a cancer immunotherapy strategy.
The latest setback is in a phase 3 trial of MSD's anti-TIGIT antibody vibostolimab and PD-1 inhibitor pembrolizumab in small cell lung cancer (SCLC), with a lack of efficacy and side effects both contributing to the decision.
An interim look at overall survival (OS) data by the KeyVibe-008 study's independent monitoring committee concluded that the fixed-dose formulation of the two drugs was likely to show no improvement over the comparator drug and caused more side effects, including immune-related adverse events.
The announcement comes a few months after MSD halted the KeyVibe-010 trial of the co-formulation as an adjuvant treatment for patients with high-risk melanoma treated with surgery – also due to immune side effects – and a few days after Bristol-Myers Squibb dropped out of a $1.56 billion TIGIT inhibitor alliance with Agenus, continuing a run of trial results and partnering decisions that have dented confidence in the class.
KeyVibe-008 enrolled 460 previously untreated patients with extensive-stage SCLC who were treated with either pembrolizumab/vibostolimab of Roche's PD-L1 inhibitor Tecentriq (atezolizumab) – both given alongside chemotherapy.
MSD – known as Merck & Co in the US and Canada – said in a statement that patients in the trial should stop ongoing treatment with the fixed-dose combination and be offered the option to be treated with Tecentriq instead, which has been approved as a front-line treatment for extensive-stage SCLC since 2019.
"Small cell lung cancer remains a difficult disease to treat, as evident by the 7% five-year survival rate and limited advancements in treatment options," said Dr Marjorie Green, head of oncology, global clinical development, at Merck Research Laboratories.
"While we hoped the results would be different, we remain committed to investigating novel approaches to treat this debilitating disease," she added.
Last year, MSD revealed that the co-formulation – given either alone or in combination with docetaxel chemotherapy –generated disappointing progression-free survival (PFS) results in the KeyVibe-002 study in patients with relapsed or refractory advanced non-small cell lung cancer (NSCLC).
It still has three phase 3 studies of the drug on the go in NSCLC settings – KeyVibe-003, KeyVibe-006, and KeyVibe-007 – and so far data reviews have not revealed any reasons to modify or change them.
MSD, meanwhile, still has other projects on the go in SCLC. The company highlighted in its statement the recent start of the IDeate-Lung02 of B7-H3-directed antibody-drug conjugate ifinatamab deruxtecan (I-DXd) – part of a large-scale alliance with Daiichi Sankyo – as well as MK-6070, a DLL3-targeting T-cell engager acquired as part of its takeover of Harpoon Therapeutics which is in phase 1/2.
Photo by Nadine Shaabana on Unsplash
