Shortly after an FDA nod for a chemotherapy combination in newly diagnosed non-small cell lung cancer, Regeneron’s Libtayo has registered another seemingly positive readout in the same setting—this time with extra help from Bristol Myers Squibb’s Yervoy. But this one won’t matter commercially.
Adding Libtayo and Yervoy to chemotherapy pared down the risk of death by 38.5%—compared with chemo alone—when used as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expressions below 50%. The dataset, along with Regeneron’s early PD-1/LAG-3 readout in NSCLC, will be presented at the ESMO Immuno-Oncology Congress 2022 next week.
The magnitude of death reduction looks better than the 29% benefit that the combination of Libatyo and chemo posted in the same EMPOWER-Lung3 trial. Last month, those study results won the regimen a broad FDA approval in first-line NSCLC regardless of PD-L1 expression status.
Still, the new analysis doesn’t bear any statistical weight and is merely “descriptive,” according to the investigators. That's because Regeneron stopped the Libatyo-Yervoy-chemo arm early to focus on the sans-Yervoy regimen.
Regeneron started the trial at a time when CTLA-4 inhibitors such as Yervoy drew interest for their potential to boost PD-1 blockade, Izzy Lowy, M.D., Ph.D., senior VP of oncology translational and clinical sciences, told Fierce Pharma last year. The company later realized that a solid anti-PD-1 agent plus standard chemo is probably enough because a CTLA-4 agent comes with additional toxicities.
That’s reflected in the fact that Merck’s Keytruda-chemo regimen is well-accepted as the standard immunotherapy in first-line NSCLC and is used more widely than Bristol’s Opdivo-Yervoy-chemo cocktail. Previously Lowy said Regeneron wouldn’t pursue approval for a Libtayo version of that BMS regimen.
Still, the latest data paint Libtayo in a positive light compared with Opdivo. In the phase 3 CheckMate-9LA trial, Opdivo, Yervoy and chemo cut the risk of death by 31% over chemo alone at an interim analysis with minimum 8.1 months of follow-up. The size of the benefit first widened to 33% at 12.7 months of follow-up and then shrank to 26% after three years.
By comparison, the Libtayo-Yervoy-chemo combo posted its own 38.5% risk reduction after a median follow-up of three years.
One important difference between the two studies is that EMPOWER-Lung3 enrolled stage 3 and stage 4 patients, whereas CheckMate-9LA only recruited only individuals with stage 4 cancer.
In this cancer setting, Regeneron has set its sights not on Opdivo but on Keytruda. Thanks to the first-line nod in November, Libtayo has become the only other-PD-1/L1 inhibitor besides Keytruda to boast a U.S. chemo combo use in first-line NSCLC regardless of PD-L1 levels or histology, plus a monotherapy approval in PD-L1-high patients.
But SVB Securities analyst Daina Graybosch, Ph.D., previously predicted that Libtayo will have a hard time penetrating the NSCLC market—not because it has bad data but because it lacks differentiating factors to persuade doctors to switch from Keytruda.
Regeneron recently gained full rights to Libtayo from its former partner Sanofi. At that time, CEO Len Schleifer, M.D., Ph.D., said the deal would give Regeneron “the freedom to explore combination opportunities in our pipeline with existing collaborators and with future partners.”
Like many other immuno-oncology players, Regeneron is working on new agents to potentially boost Libtayo. At ESMO I-O 2022, the company is presenting early phase 1 data for its LAG-3 candidate, fianlimab, in combination with Libtayo in stage 3b to c or stage 4 NSCLC.
Among 15 PD-1/L1-naïve patients, the combo triggered a response in 4 (26.7%) patients after a median follow-up of 8.5 months. In that cohort, six patients had never tried any treatment before, and the PD-1/LAG-3 combo shrank tumors in three of them. And all three patients with high PD-L1 expression of at least 50% responded to treatment.
And of the 15 patients who had received prior PD-1/L1 agents, the combo shrank tumors in just one (6.7%) patient after a median follow-up of 5.4 months.
In their conclusion, the trial investigators said the Regeneron combo showed “promising signs of clinical activity with durable response” among PD-1/L1-naïve patients and in participants with high PD-L1 expression, seemingly suggesting the company should focus on those patients for future development. The combo also showed no additional safety problems compared to Libtayo monotherapy, the researchers noted.