What infeasible trial? Lilly shows Roche how it's done with positive Retevmo readout in thyroid cancer

It was only a few weeks ago when Roche said a phase 3 study testing its RET inhibitor Gavreto in a type of thyroid cancer was not doable. Now, Eli Lilly has revealed that a similar trial of its own Retevmo was not only feasible but positive.

Tuesday, Lilly said its Retevmo has beaten a physician’s choice of other targeted therapies at preventing progression or death in patients with newly diagnosed RET-mutant medullary thyroid cancer (MTC).

Retevmo pulled off the progression-free survival (PFS) win over either Exelixis’ Cabometyx or Sanofi’s Caprelsa, Lilly said. The improvement was statistically significant and clinically meaningful, according to the drugmaker.

The positive readout means the phase 3 LIBRETTO-531 trial has hit its main goal at an interim analysis. The trial is designed to provide confirmatory evidence to turn Retevmo’s accelerated approval in MTC into a full nod.

In Tuesday’s release, Lilly didn’t touch on how Retevmo performed at extending patients’ lives or give any details about its regulatory plan. The new data “suggest Retevmo should be considered the preferred first-line treatment for people with advanced RET-mutant medullary thyroid cancer,” David Hyman, M.D., chief medical officer of Lilly’s oncology unit, said in a statement.

Retevmo won its MTC nod in 2020 based on tumor shrinkage data in both treatment-naïve and experienced patients. At that time, the FDA required Lilly to run a randomized trial using PFS as a key secondary endpoint to confirm the drug’s clinical benefit. 

MTC represents a niche market. It accounts for only 1% to 2% of thyroid cancers in the U.S., and RET mutations are found in 60% to 90% of MTC tumors depending on whether the disease is inherited.

Retevmo’s readout comes shortly after oncology juggernaut Roche said it would withdraw Blueprint Medicines-partnered Gavreto from the U.S. RET-mutant MTC market. At the time, Roche said its own phase 3 confirmatory trial coded AcceleRET-MTC was no longer feasible.

Roche’s AcceleRET-MTC study was never activated even though the details of the trial were made public in February 2021. Gavreto won its accelerated approval in MTC three months ahead of that trial reveal.

By comparison, Lilly unveiled its trial plan in late 2019 and the study officially kicked off in February 2020, even before Retevmo’s accelerated approval.

Seeking to tighten regulations around accelerated approvals, the FDA’s oncology department recently started asking drug developers to have their confirmatory trials well underway at the time of accelerated approvals. This requirement is aimed at avoiding failures to follow through with post-marketing commitments, like in the case of Roche’s AcceleRET-MTC.

Beyond thyroid cancer, Retevmo is also coming off a positive readout in RET fusion-positive advanced non-small cell lung cancer. When used as an initial treatment, the RET inhibitor topped chemotherapy—used with or without Merck’s Keytruda—on PFS, Lilly said earlier this month.

Gavreto’s own first-line NSCLC trial, AcceleRET-Lung, has yet to report data. Because of a dim sales outlook, Roche recently decided to return Gavreto to Blueprint.