Highlights in lung cancer from ASCO 2026: LIBRETTO-432, CROWN, and more

There are four abstracts that I will talk about there.

The first one is a phase three study, the Libretto 432, which tests the cell percalinib, a RET inhibitor for patients with nosomal cell lung cancer, resected stage 1B to 3A.

Oseprocarb was given at the same dosage as in a metastatic setting, so 160 milligrams twice a day for up to three years.

These results were somewhat expected because they're compared with placebo in the adjuvant setting, and we've seen some benefit, huge benefit, actually, with other drugs, something about tolectinib for ALK, fusion-positive tumors, or ozimertinib for regioform mutant lost muscle lung cancer.

So the median EFS, which was the primary endpoint of the study, was not reached with a median follow-up of 24 months for cetpercatinib.

So the median follow-up was actually shorter than the planned duration of cetpercatinib with an hazard ratio of 0.17.

So we'll see whether these curves will tend to reconverge.

after the plan duration of the drug, after three years, as we've seen with osimertinib in the ADARA trial.

And we will see if there's room for extending this, the duration of therapy, after three years, or maybe indefinitely for this patient.

But these results are very important, and I hope I will see the same study for other oncogene-addicted populations, such as HER2, KRAS, ROS1, etc., The other two trials testing KRAS-Utl-C inhibitors in patients with KRAS-Utl-C mutant non-mostellar cancer, in the first line setting, one was the CRAS-Sendo 170 trial, which tests Dabrasib plus Pembrolizumab in two cores, one core with PD-L1 positive and one core with PD-L1 negative tumors.

The results were quite impressive in terms of efficacy with an objective response rate of 70%.

And a median progressional free survival of 19 months.

So very impressive.

The objective response rate actually was 73% in the period 1 positive and 70% in period 1 negative.

So very similar among the two.

And the PFS of 18 months was in the period 1 positive.

The population was not reported for a negative population, but still very, very promising efficacy.

The concern here is in terms of safety with this combining the carotid ulcer inhibitor with immunotherapy.

We've seen previous trials showing concerning safety profile.

In this trial, there were 65% of grade 3 or 4 patients.

Theratoma-related adverse events, mostly diarrhea of any grade in 75% of patients, grade 3 or 4 in 60% of them, and also other gastrointestinal toxicities such as nausea or vomiting.

And also we've seen roughly 20% of cases with elevated liver functional tests, AST or ALT, increase of grade 3 or 4.

This is mostly the limitation of applying this drug to the general population, but we'll see in a larger course if this is confirmed.

And then the other trial is testing LS-RASIB in patients with keratocytosis mutandole muscle lung cancer.

LS-RASIB is another specific keratocytosis inhibitor.

There are four abstracts that I will talk about there.

The first one is a phase three study, the Libretto 432, which tests the cell percalinib, a RET inhibitor for patients with nosomal cell lung cancer, resected stage 1B to 3A.

Oseprocarb was given at the same dosage as in a metastatic setting, so 160 milligrams twice a day for up to three years.

These results were somewhat expected because they're compared with placebo in the adjuvant setting, and we've seen some benefit, huge benefit, actually, with other drugs, something about tolectinib for ALK, fusion-positive tumors, or ozimertinib for regioform mutant lost muscle lung cancer.

So the median EFS, which was the primary endpoint of the study, was not reached with a median follow-up of 24 months for cetpercatinib.

So the median follow-up was actually shorter than the planned duration of cetpercatinib with an hazard ratio of 0.17.

So we'll see whether these curves will tend to reconverge.

after the plan duration of the drug, after three years, as we've seen with osimertinib in the ADARA trial.

And we will see if there's room for extending this, the duration of therapy, after three years, or maybe indefinitely for this patient.

But these results are very important, and I hope I will see the same study for other oncogene-addicted populations, such as HER2, KRAS, ROS1, etc., The other two trials testing KRAS-Utl-C inhibitors in patients with KRAS-Utl-C mutant non-mostellar cancer, in the first line setting, one was the CRAS-Sendo 170 trial, which tests Dabrasib plus Pembrolizumab in two cores, one core with PD-L1 positive and one core with PD-L1 negative tumors.

The results were quite impressive in terms of efficacy with an objective response rate of 70%.

And a median progressional free survival of 19 months.

So very impressive.

The objective response rate actually was 73% in the period 1 positive and 70% in period 1 negative.

So very similar among the two.

And the PFS of 18 months was in the period 1 positive.

The population was not reported for a negative population, but still very, very promising efficacy.

The concern here is in terms of safety with this combining the carotid ulcer inhibitor with immunotherapy.

We've seen previous trials showing concerning safety profile.

In this trial, there were 65% of grade 3 or 4 patients.

Theratoma-related adverse events, mostly diarrhea of any grade in 75% of patients, grade 3 or 4 in 60% of them, and also other gastrointestinal toxicities such as nausea or vomiting.

And also we've seen roughly 20% of cases with elevated liver functional tests, AST or ALT, increase of grade 3 or 4.

This is mostly the limitation of applying this drug to the general population, but we'll see in a larger course if this is confirmed.

And then the other trial is testing LS-RASIB in patients with keratocytosis mutandole muscle lung cancer.

LS-RASIB is another specific keratocytosis inhibitor.