Clinical Trials Arena

Eli Lilly meets primary endpoint in LIBRETTO-431 study for NSCLC

Eli Lilly’s LIBRETTO-431 study demonstrated a statistically significant improvement in progression-free survival for NSCLC patients.

Eli Lilly has met the primary endpoint in the LIBRETTO-431 study evaluating Retevmo versus platinum-based chemotherapy plus pemetrexed with or without Keytruda.

LIBRETTO-431 (NCT04194944) is a Phase III, randomised, open-label trial evaluating Retevmo (selpercatinib) versus platinum-based chemotherapy, using cisplatin or carboplatin, and pemetrexed with or without Keytruda (pembrolizumab) in patients with non-small cell lung cancer (NSCLC).

A total of 261 patients with advanced or metastatic RET fusion-positive NSCLC who received no prior systemic therapy were enrolled in the trial. Patients were randomised 2:1 to receive either selpercatinib or platinum-based (carboplatin or cisplatin) and pemetrexed therapy with or without Keytruda as initial treatment.

Results of LIBRETTO-431 Phase III study

The study demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS). This result was based on a pre-specified interim efficacy analysis conducted by an independent data monitoring committee (IDMC).

Adverse events observed for Retevmo were generally consistent with those identified across the previously reported programmes.

Warnings and precautions for several adverse events are detailed in the label for Retevmo, including hepatotoxicity (evidence of liver dysfunction), interstitial lung disease (ILD)/pneumonitis, hypertension, QT interval prolongation, haemorrhagic events, hypersensitivity, tumour lysis syndrome, risk of impaired wound healing, hypothyroidism, and embryo-foetal toxicity.

These results build on the data from LIBRETTO-001, the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor, which spans 16 countries and 85 sites, and includes a dose escalation phase (Phase I) and a dose expansion phase (Phase II). In this trial, Retevmo demonstrated clinically meaningful and durable responses across a variety of tumour types in patients with RET-driven cancers.

Chief medical officer of Loxo@Lilly Dr David Hyman said: "This clinically meaningful achievement of improved outcomes underscores the importance of timely and comprehensive genomic testing to inform initial treatment decisions for all patients with NSCLC. The results of this study provide further confirmation that RET status – like EGFR, ALK, and others in the family of lung cancer oncogenic drivers – should be known prior to initiating therapy.”