Third strike for GSK/Merck as bintrafusp alfa flubs again

GlaxoSmithKline's big gamble on Merck KGaA's bintrafusp alfa has gone from bad to worse, after the drug failed yet another mid-stage trial.

The latest disappointment has come from the phase 2 INTR@PID BTC 055 study of the drug alongside chemotherapy as a first-line treatment for patients with locally advanced or metastatic biliary tract cancer (BTC), which has been abandoned early.

An interim look at the data by the trial's independent monitoring committee concluded that adding bintrafusp alfa to a gemcitabine/cisplatin regimen was unlikely to show any improvement on overall survival than the chemotherapy on its own.

The failure comes after bintrafusp alfa missed the mark in a phase 2 trial as a second-line monotherapy for BTC patients who failed first-line chemotherapy in March, when GSK and Merck suggested the first-line study was the brightest prospect for the drug.

In January, it also failed to show any improvement over Merck & Co/MSD's checkpoint inhibitor Keytruda (pembrolizumab) in previously-untreated patients with PD-L1-positive non-small cell lung cancer (NSCLC).

That trial was always going to be ambitious taking on Keytruda in its NSCLC heartland, which accounts for a large proportion of its $14 billion sales last year, but the double failure in BTC looks to have ended GSK and Merck's hopes of finding a role for bintrafusp alfa in an indication with no immunotherapy rivals.

GSK bagged co-development and co-marketing rights to the bifunctional fusion protein – which combines anti-PD-L1 and TGF beta inhibition – in a $4.2 billion deal signed in 2019 that kicked off with a $363 million upfront payment.

Most of the value of the deal was at the back end in milestone payments for hitting development and commercial targets of course, and with three fails to date GSK's total investment is probably fairly modest so far.

Merck issued a terse statement on the latest disappointment, saying merely that it was notifying health authorities and trial investigators of the decision to terminate the study, and thanking the participants and their families.

Merck's pipeline also lists ongoing phase 2 trials of bintrafusp alfa in first-line NSCLC alongside chemo, second-line cervical cancer, and HMGA2-positive triple-negative breast cancer (TNBC), but with three strikes down the programme is looking decidedly shaky.