New non-small cell lung cancer (NSCLC) treatments recommended by EMA (pralsetinib) and FDA (mobocertinib)

The CHMP adopted a positive opinion, recommending the granting of a conditional marketing authorisation for Gavreto(pralsetinib)- 100 mg hard capsules - of Roche Registration GmbH, for the treatment of patients with rearranged during transfection (RET)-fusion positive non-small cell lung cancer (NSCLC). 

The indication is: Gavreto is indicated as monotherapy for the treatment of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor.

Gavreto is a RET receptor tyrosine kinase inhibitor targeting oncogenic RET fusion proteins (KIF5B-RET and CCDC6-RET). Certain point mutations in RET or chromosomal rearrangements involving in-frame fusions of RET with various partners can result in constitutively activated chimeric RET fusion proteins that can act as oncogenic drivers by promoting cell proliferation of tumour cell lines.

The benefits of Gavreto are its objective response rate and response duration in patients with RET-fusion positive NSCLC as observed in a pivotal phase I/II, open-label, multi-cohort, single-arm study.

The most common side effects are anaemia, increased aspartate aminotransferase, neutropenia, constipation, musculoskeletal pain, fatigue, leukopenia, increased alanine aminotransferase and hypertension.

In US, the FDA grants accelerated approval to Exkivity (mobocertinib) of Takeda Pharmaceuticals Inc., for metastatic non-small cell lung cancer. 

The indication is: Exkivity is indicated in locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to select patients with the above mutations for mobocertinib treatment.

Approval was based on Study 101, an international, non-randomized, open-label, multicohort clinical trial (NCT02716116) which included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Efficacy was evaluated in 114 patients whose disease had progressed on or after platinum-based chemotherapy. Patients received mobocertinib 160 mg orally daily until disease progression or intolerable toxicity. The main efficacy outcome measures were overall response rate (ORR) according to RECIST 1.1 as evaluated by blinded independent central review (BICR) and response duration. The ORR was 28% (95% CI: 20%, 37%) with a median response duration of 17.5 months (95% CI: 7.4, 20.3).