Jazz, Roche combo cleared by FDA for lung cancer

A regimen based on Jazz Pharma and PharmaMar's Zepzelca and Roche's Tecentriq has been approved in the US as a maintenance therapy for extensive-stage small-cell lung cancer (ES-SCLC).

The approval means that DNA-disrupting alkylating agent Zepzelca (lurbinectedin) and PD-L1 inhibitor Tecentriq (atezolizumab) can now be used in ES-SCLC patients whose disease has not progressed after first-line induction therapy with Tecentriq and chemo.

The go-ahead is based on the results of the IMforte study, reported at the ASCO congress earlier this year, which showed that the combination more than doubled progression-free survival (PFS) to 5.4 months compared to 2.1 months for Tecentriq alone. That was accompanied by a 27% improvement in overall survival (OS), coming in at 13.2 months and 10.6 months, respectively.

Tecentriq has been credited with transforming the treatment of ES-SCLC when it was approved as a first-line treatment in 2019, and was joined in that setting the following year by AstraZeneca's PD-L1 inhibitor Imfinzi (durvalumab).

Nevertheless, despite the use of these cancer immunotherapies, the long-term prognosis for people with the disease remains poor, as there is a high risk of relapse. Previously, Zepzelca was approved as a second-line option for ES-SCLC patients after treatment progression with platinum-based induction chemo.

The approval of Zepzelca/Tecentriq is the first for a combination therapy in the first-line maintenance setting, according to Roche, which also said that the cancer guidelines in the US have already been updated to include the regimen as the "preferred option" after Tecentriq and chemo.

The label extension looks likely to reinject growth in Zepzelca sales, which reached $320 million last year but contracted in the first half of this year to $137 million.

The fall has been attributed to competition in the second-line SCLC space from therapies like Amgen's bispecific drug Imdelltra (tarlatamab), which was approved by the FDSA last year, as well as treatment protocol updates that delayed progression of patients with first-line, limited-stage SCLC to the second-line setting.

"ES-SCLC patients have good initial responses but then quickly progress," commented Jazz's head of R&D Rob Iannone. "Extending the time to progression, and ultimately survival, will be clinically valuable, in particular in this fast-moving cancer."

SCLC is the most aggressive form of any lung cancer, accounting for around 15% of all cases, and is characterised by rapid progression and poor survival. About 70% of people are diagnosed when SCLC has already spread beyond its original site.