Interim miss slows IO Biotech

IO Biotech had hoped to file for accelerated approval of its immunotherapy IO102-IO103 in first-line melanoma, but that plan has now been dashed by the Keynote-D18 trial not meeting the bull case of outstandingly high efficacy resulting in a stop at interim analysis.

The study, testing IO102-IO103 plus Keytruda, versus Keytruda alone, didn’t show a statistically significant improvement on overall response rate at interim, the company said on Friday, and will thus continue unchanged to full analysis next year.

True, IO had already played down the possibility of such an early success, noting before the readout that an ORR win was a long shot; the statistical bar was high, with the interim analysis requiring a p value of 0.005 or lower versus Keytruda monotherapy to be deemed a success.

That’s because most of the study’s alpha has been preserved for the primary endpoint of progression-free survival, due to read out in the first half of 2025. The PFS analysis will be conducted when 226 events of disease progression or death have been reported; the study is 89% powered to detect a 35% reduction in events.

IO reckons it has a cash cushion: at the last count it had $101m in the bank, enough to get it into the fourth quarter of 2025 and past the PFS readout. But any delay – not uncommon in event-driven trials – could cause investor jitters.

The company is based in Denmark but listed in the US, and saw its shares fall 13% after market, indicating that at least some of its backers had hoped for an early positive ORR result.

The next event for IO will be ESMO, when it will present a poster on IO102-IO103 plus Keytruda in head and neck cancer from a phase 2 basket trial; NSCLC data from the same trial are due later this year.

IO102-IO103 is an off-the-shelf project comprising IDO and PD-L1 peptide antigens; it’s designed to activate T cells specific for those antigens, thereby boosting patients’ immune systems.