2018 is here. Now get ready for ‘market-defining’ I-O readouts

Keytruda Opdivo
Merck and Bristol-Myers Squibb, makers of Keytruda and Opdivo, respectively, are each expecting key data early this year.

If you thought 2017 was a game-changer for immuno-oncology, just wait. In the first half of 2018 alone, each of the four major players—Merck, Bristol-Myers Squibb, Roche and AstraZeneca—is expecting a phase 3 data readout that Bernstein analyst Tim Anderson says will be “market-defining.” Here’s an up-close look at what to watch for as the new year gets rolling.

  • AstraZeneca: Last summer, AstraZeneca presented the first phase 3 data for a combination of a PD-1/L1 checkpoint inhibitor and a CTLA4 drug as a treatment for previously untreated patients—and it wasn’t positive. In a trial dubbed Mystic, a pairing of its Imfinzi PD-L1 with candidate tremelimumab failed to stave off lung cancer progression better than chemotherapy or Imfinzi alone. AZ has insisted, though, that the progression-free survival shortfall doesn’t mean the combo won’t come out ahead when it comes to extending patients' lives, and that’s the key Mystic data industry watchers are still waiting for. If the British pharma giant succeeds on the overall survival front, its duo could get a shot at taking on Merck’s Keytruda-chemo combo in the ultralucrative front-line lung cancer setting. And if it doesn't, that doesn’t bode well for Bristol-Myers Squibb, which is also trialing a CTLA4 combo.
     
  • Bristol-Myers Squibb: Bristol-Myers’ own marriage of PD-1 and CTLA4, an Opdivo-Yervoy combo, is almost due for results of its own from the CheckMate-227 trial. And those results will be equally important to AstraZeneca’s in determining whether CTLA4 has a place in the treatment of first-line lung cancer. After all, while investors and analysts have looked to AstraZeneca’s trial for insight on the viability of the CTLA4 approach, it’s still completely possible that one CTLA4 combo could succeed where the other fails. Meanwhile, another first-line failure is the last thing Bristol-Myers needs after missing its shot at an Opdivo monotherapy nod in the lung cancer field. With that misstep, BMS ceded its overall lead in the lung-cancer race to Merck, whose Keytruda now boasts two front-line nods.
     
  • Merck: Just because Merck’s Keytruda is running the first-line lung cancer show for now doesn’t mean the company isn’t pressing full-speed ahead to rack up additional indications. One potential avenue for doing that? Its Keynote-042 study, which Anderson has called a “sleeper trial that has been comparatively ‘off the radar screen’" for many investors. That trial, he’s pointed out, has the potential to roughly triple the number of untreated lung cancer patients eligible for Keytruda monotherapy; right now, the med is approved only for patients whose tumors express high levels of PD-L1, but if all goes well in Keynote-042, the entire population of PD-L1-positive patients—who make up about 70% of first-line patients with nonsquamous non-small cell lung cancer—could eventually fall into Merck’s patient pool. Outside of lung cancer, Merck is also awaiting data from the Echo-301 trial, which is testing Keytruda alongside Incyte’s closely watched IDO inhibitor, epacadostat, in melanoma.
     
  • Roche: And just because Merck has succeeded with its Keytruda-chemo combo doesn’t mean Roche can count on the same results from a combo of chemo and its PD-L1 med Tecentriq. And even if the pairing can prove successful in the clinic, it’ll be up to Roche to provide some indication that its cocktail works better than the Keytruda duo if it wants to snap up market share. To do that, the Swiss drugmaker will need strong results from three of its Impower studies, numbered 130, 131 and 132, which are examining Tecentriq in various chemo cocktails and among both squamous and nonsquamous patients.