Potential lung cancer use for Novartis' melanoma combo

Already approved in melanoma, Novartis' Tafinlar and Mekinist combination could also be used in non-small cell lung cancer (NSCLC) with the genetic mutation it targets, according to new data.

The phase 2 trial data shows Tafinlar (dabrafenib) and Mekinist (trametinib), acquired from GlaxoSmithKline last year as part of a multi-billion dollar asset swap deal, had an effect in patients with BRAF V600E-mutation positive disease.

Data presented at the American Society of Clinical Oncology (ASCO) conference in Chicago followed separate phase 3 data showing the combination conferred a significant survival benefit compared with Tafinlar alone in first line in BRAF V600E positive advanced melanoma.

Only 1-2% of NSCLC patients have the mutation – but it is associated with more aggressive tumours and a poorer prognosis, independent of smoking status.

The lung cancer trial's principal investigator, David Planchard, of the Cancer Institute Gustave-Roussy, Villejuif, France, said results confirmed that BRAF V600E is the fourth actionable biomarker in NSCLC after EGFR, ALK and ROS-1.

In the study, patients treated with Tafinlar plus Mekinist demonstrated an overall response rate (ORR) of 63%.

In the multicentre, non-randomised, open-label study, 57 patients with metastatic NSCLC who had the BRAF V600E mutation and failed at least one line of chemotherapy took 150 mg of Tafinlar twice daily and 2 mg of Mekinist once daily.

The primary endpoint of the trial was investigator-assessed ORR, and key secondary endpoints were duration of response (DoR) and progression-free survival (PFS). Independent review response rates were consistent with investigator-assessed response.

The investigator-assessed median DoR and PFS were 9.0 months and 9.7 months respectively.

36 of 57 patients (63%) demonstrated a clinical response; of these patients, 50% (18 of 36) continued to respond to treatment at the time of analysis.

The most common adverse events were pyrexia, nausea, vomiting, diarrhoea, asthaenia, decreased appetite, dry skin, chills, peripheral oedema, cough and rash. Four patients (7%) died from fatal adverse events not related to study treatment as assessed by the investigator.

Novartis also presented phase 1 data from capmatinib, which has prompted phase 2 studies exploring cMET dysregulation in advanced NSCLC.

The drug is a potent and selective oral cMET inhibitor, licensed by Novartis from Incyte Corporation.

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