It's often a bad sign when a clinical trial stops early. Not so for Sanofi and Regeneron Pharmaceuticals. On Thursday, the partners said they were pumping the brakes on a pivotal study of a Libtayo-chemotherapy combo in lung cancer because the initial results were just that good.
Sanofi and Regeneron signaled the early end to their phase 3 Libtayo trial in advanced non-small cell lung cancer (NSCLC) based on the study's independent data monitoring committee's recommendation after a prespecified interim analysis. The companies now plan to use the data for approval filings in Europe and the U.S.
Back in February, Libtayo broke into the highly competitive lung cancer market when the FDA approved the PD-1 inhibitor as a monotherapy for patients with newly diagnosed, locally advanced or metastatic NSCLC whose tumors have high levels of PD-L1 expression. The results released today are from the Empower-Lung 3 study, which is also in first-line patients but those with any level of PD-L1 expression and combined Libtayo and chemotherapy. Libtayo on top of platinum-doublet chemotherapy significantly improved overall survival versus chemotherapy in these patients.
The February green light put Libtayo on a collision course with Merck & Co.’s immunology superstar Keytruda. At the time of Libtayo’s lung cancer nod, SVB Leerink analyst Geoffrey Porges forecasted less than $1 billion in Libtayo peak sales in the disease, though he hinted that a future combo regimen could improve the drug's prospects.
RELATED: Lower Libtayo's price before Chinese PD-1s do, says analyst in open letter to Regeneron CEO
Solo immuno-oncology drugs are currently only given to patients who can't tolerate chemo, and standard of care has pivoted to Keytruda plus chemotherapy. In the Keynote-407 study, which looked at a Keytruda-chemo combo regimen in squamous NSCLC, Keytruda cut death risk by 36% over chemo alone at an interim analysis. That reduction fell to 29% at final analysis. For its part, Libtayo’s Empower Lung-3 study is assessing the drug in patients with both squamous and non-squamous disease.
In nonsquamous NSLC, Keytruda plus chemo has demonstrated an impressive 51% reduction in death over chemo alone at interim analysis.
The interim analysis of the 466-patient Empower-Lung 3 trial showed the Libtayo-chemo combo slashed the risk of death by 29% versus chemotherapy alone. Median overall survival for patients on the Libtayo regimen was 22 months, compared to 13 months in the chemotherapy-alone cohort.
Notably, the phase 3 assessed the drug in patients with myriad tough-to-treat disease characteristics, Miranda Gogishvili, M.D., an oncologist and trial investigator, said in a statement.
Over the course of the 108-week study, patients received an infusion of either placebo or Libtayo 350mg every three weeks, plus platinum-doublet chemotherapy administered every three weeks for four cycles. On top of the overall survival endpoint, the study looked at progression-free survival as a coprimary endpoint and assessed secondary endpoints like objective response rate and best overall response.
Prior to the drug's lung cancer nod in February, Libtayo was confined to the realm of skin cancer. Its NSCLC monotherapy nod marked an important step on the drug's potential path toward blockbuster sales, but an approval for a combo regimen could be the real clincher.
Aside from its lung cancer nod, Libtayo also won the FDA's blessing to treat basal cell carcinoma in February. Sanofi and Regeneron are also angling for a win in cervical cancer, where Libtayo solo was recently shown to slash the risk of death by 31% over chemotherapy in recurrent or metastatic cervical cancer that had progressed on platinum-based chemo.
Editor's note: This story was updated with additional data on Keytruda.