Selpercatinib in RET+ NSCLC: LIBRETTO-431

The Libretto 431 study presented during ESMO 2023 compared Selpercatinib versus standard chemo plus pembrolizumab for newly diagnosed red fusion-positive non-small cell lung cancer.

Author: Dr Herbert Ho Fung Loong (on-camera comments) - Courtesy of

During ESMO 2023, I've had the pleasure of presenting our groups data which is the Libretto 431 study which is actually a first line study of the use of supper catching it versus standard chemotherapy plus pembrolizumab in patients with newly diagnosed red fusion positive non small cell lung cancer.

So by way of background red fusion accounts for about 2% of all non small cell lung cancers.

And previously at least prior to the knowledge of knowing the fact that RET as a driver for most of these patients, the standard chemotherapy will be the KEYNOTE 189 trial or study a regimen which will be the use of pembrolizumab together with pemetrexid and together with a platinum based chemotherapy.

Having said that, we've had prior investigations especially in the Libretto 001 trial where patients with RET fusion also benefited from the use of RET inhibitors specifically salpercatinate with very good response and duration of response.

So therefore we decided to design as well as conduct this clinical trial in a phase three open label head to head comparison setting.

This trial took place over throughout actually the COVID pandemic during March 2020 to 2022 at which .261 patients who were recruited around the world.

The key findings of the study is that the progression free survival of patients who were treated with salprocatinib is superior than those who were treated with the chemotherapy plus parabolizumab treatments.

Specifically, the progression free survival of patients treated with salprocatinib was 24.8 months as opposed to 11.2 months in the chemotherapy plus Membolisma group.

The hazard ratio was 0.46.

Moreover, in terms of the treatment, there was also improvement in terms of the reduction of brain metastasis in these patients.

Within the patient population itself, on recruitment, 20% of the patients actually had brain metastasis which was equally distributed in the two arms.

But in actual fact for the patients who actually had brain metastasis, the cumulative increase in the number of brain progression was significantly lower.

Both in the patients who had pre-existing brain metastasis or did not have brain metastasis in the beginning.

In patients who were treated with saprocatinib, Specifically for patients who did not have brain metastasis but were treated with saprocatinib, after a 12 month period, only 1% of the patient developed brain metastasis and this is as opposed to about 14% in the patients who were on the chemotherapy plus pebbleizumab treatment.

In terms of safety profile, this is a drug that we are already well familiarized given the fact that the drug is approved in over 40 jurisdictions around the world.

The most common safety profile issues includes transaminitis including ASTALT changes.

There have been evidence of hypertension as well as peripheral edema.

These are all generally well controlled with dose interruption as well as other dose modifications.

The patients who had chemotherapy had the common chemotherapy toxicities including myelosuppression.

Overall with this particular clinical trial, I think we now have evidence that the use of Salpercatinib in red fusion positive non small cell lung cancer is an effective treatment especially in the first line setting.

And there is definitely a call for us to do next generation sequencing for our newly diagnosed non small cell lung cancer patients.

So we can identify this 2% of patients and benefit from a much more effective treatment than standard of care that we have right now.