Pivotal data sets up Tecentriq filing in small cell lung cancer

Roche’s PD-L1 inhibitor Tecentriq has become the first cancer immunotherapy to improve survival in extensive-stage small cell lung cancer (ES-SCLC), putting it on course to end a 20-year drought for new therapies.

The company says it will press ahead with regulatory filings in the US, Europe and elsewhere based on the results of the IMpower133 study, which looked at using PD-L1 inhibitor Tecentriq (atezolizumab) as a front-line therapy in combination with chemotherapy for ES-SCLC.

Details of the primary efficacy measures aren’t being disclosed just yet, but Roche says its drug achieved a statistically significant reduction in both overall survival (OS) and progression-free survival (PFS) at the interim analysis – and that should be enough to secure regulatory approvals.

Small cell lung cancer is less common that the non-small cell lung cancer (NSCLC) variant but tends to be more aggressive, growing more quickly and spreading to other parts of the body earlier. Overall it is fairly responsive to chemotherapy and radiotherapy, but relapse rates are high and median survival low –often a year or less in extensive-stage disease – and two-thirds of patients have advanced disease at diagnosis. Typically, 5% or less of ES-SCLC patients – in whom the tumour has spready beyond the lung and adjacent lymph nodes – are still alive after five years.

“These are the first positive Phase III survival results for any immunotherapy-based combination in the initial treatment of ES-SCLC, a particularly difficult-to-treat type of disease,” said Roche’s chief medical officer Sandra Horning.

If approved, adding ES-SCLC to Tecentriq’s indications gives Roche an opportunity to carve out another piece of the lung cancer market without competition from other checkpoint inhibitors such as Merck & Co’s Keytruda (pembrolizumab) and Bristol-Myers Squibb’s Opdivo (nivolumab), which reached the market first and are way head in terms of market penetration.

Merck already has phase 1b data in hand for Keytruda in ES-SCLC, although its trial used Keytruda as a second-line therapy in heavily pre-treated patients. The company is currently running a phase III trial (KeyNote-604) of its PD-1 inhibitor as a first-line therapy for ES-SCLC in combination with chemotherapy.

Meanwhile, BMS recently filed a US marketing application for Opdivo in combination with its CTLA4 inhibitor Yervoy (ipilimumab) as a treatment for patients with progressive SCLC after two or more earlier lines of therapy, based on phase I/II data from the CheckMate-032 study, and also has two phase III trials ongoing in the second-line setting and a phase II trial on the go for previously-untreated ES-SCLC.

Recent market entrant AstraZeneca is also testing its PD-L1 inhibitor Imfinzi (durvalumab) in first-line ES-SCLC, testing the drug as a monotherapy and in combination with its investigational CTLA4 inhibitor tremelimumab on top of background chemotherapy in a late-stage trial.