An FDA approval is setting a new benchmark for future treatment for first-line small cell lung cancer.
The FDA has greenlighted Jazz Pharmaceuticals’ Zepzelca, used in combination with Roche’s Tecentriq, as a first-line maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC), the agency said Thursday. The approval also applies to Tecentriq Hybreza, a subcutaneous version of the Roche PD-L1 inhibitor.
First-line maintenance treatment is for patients who have not progressed after initial induction therapy. Before Thursday’s approval, Tecentriq in combination with chemotherapy, followed by Tecentriq alone, has been a standard of care in first-line ES-SCLC. The newly FDA-approved regimen now adds Jazz’s Zepzelca, which is also a chemotherapy drug, during the maintenance phase.
“For people with extensive-stage small cell lung cancer and their families, the period after induction therapy is often filled with uncertainty, given the high risk of relapse,” Roy Herbst, M.D., Ph.D., from the Yale School of Medicine said in an Oct. 3 statement. The FDA approval of Tecentriq and Zepzelca “may lead to a meaningful shift in how we manage this challenging disease and gives us a new tool to help to delay disease progression and extend survival,” he added.
Herbst was a member of the steering committee for the phase 3 IMforte trial that convinced the FDA of Zepzelca and Tecentriq’s treatment effect. Adding Zepzelca reduced the risk of death by 27% more than Tecentriq alone during the maintenance phase. Those who got the combo lived a median 13.2 months, versus 10.6 months among patients in the Tecentriq arm.
Patients on the combo also had a 46% lower risk of cancer progression or death. The median progression-free survival time was 5.4 months for the combo versus 2.1 months for Tecentriq alone.
When the data were shared at the American Society of Clinical Oncology (ASCO) annual meeting this year, ASCO Chief Medical Officer Julie Gralow, M.D., noted that there’s still room for improvement in first-line ES-SCLC as the regimen’s progression-free survival is still quite short.
Nevertheless, the FDA approval, along with a recent addition as a preferred regimen on the National Comprehensive Cancer Network (NCCN) guidelines, is making Tecentriq-plus-chemo, followed by Tecentriq and Zepzelca, as the new efficacy benchmark in first-line ES-SCLC. The NCCN recommendation for the new combo is currently rated at category 2A, which is lower than the original Tecentriq regimen’s category 1.
While near-term applications with the FDA do not have to produce a direct head-to-head comparison with the regimen, industry watchers and research doctors will certainly compare any new data in first-line ES-SCLC with the IMforte regimen.
This will affect views on Amgen’s DeLLphi-305 trial for adding the DLL3 T-cell engager Imdelltra to AstraZeneca’s Imfinzi also in the first-line maintenance setting. The trial, which kicked off in June 2024, has Imfinzi maintenance alone as the comparator arm.
It will also affect future interpretation of results from BioNTech and its partner Bristol Myers Squibb’s relatively new phase 3 Rosetta Lung-01 trial for their PD-L1xVEGF bispecific pumitamig (BNT327) in first-line ES-SCLC.