Jazz Pharmaceuticals contends that its alkylating agent Zepzelca significantly improved both overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, when used as a front-line maintenance therapy with Roche’s Tecentriq.
Jazz on Tuesday unveiled topline findings from the Phase III IMforte study, demonstrating that its intravenous drug Zepzelca, when given with Roche’s Tecentriq, can significantly boost survival as a first-line maintenance therapy in patients with extensive-stage small cell lung cancer.
The company did not provide specific data in its announcement, noting only that the Zepzelca-based combo regimen elicited a “statistically significant improvement” in overall survival and progression-free survival—both primary endpoints of IMforte—compared with Tecentriq alone.
In terms of safety, IMforte found the Zepzelca combo to be generally well-tolerated, with an adverse event profile consistent with that of the known toxicities of the individual agents. There were no new signals of concern detected, according to the company.
Jazz CMO Rob Iannone in a statement called the results “highly encouraging,” noting that they also “demonstrate the potential of this regimen to delay disease progression and extend survival for patients with this aggressive disease.” The company will use IMforte’s data to support a supplemental New Drug Application for Zepzelca, which it plans to file in the first half of 2025 in the pursuit of a first-line maintenance expansion for the drug.
Jazz and partner Roche will also submit IMforte’s data for presentation at an upcoming medical congress.
Zepzelca is an intravenously administered alkylating drug that works by binding to and bending the DNA, restricting the replication and repair of genetic material and ultimately leading to cell death. This mechanism of action allows Zepzelca to target and eventually destroy cancer cells.
The FDA first approved Zepzelca in June 2020 under its accelerated pathway, allowing the use of the drug for the treatment of metastatic small cell lung cancer (SCLC) patients who had progressed on or after platinum chemotherapy. As part of its obligations under the accelerated pathway, Jazz ran the Phase III ATLANTIS trial to serve as Zepzelca’s confirmatory study but announced in December 2020 that the drug fell short of its primary endpoint.
Still, in October 2022, the FDA decided to uphold Zepzelca’s accelerated approval, noting that dosing differences in ATLANTIS—which used a lower dose—could likely be the reason why it failed. The FDA’s decision also came despite a citizen petition from law firm Foley Hoag, asking the regulator to pull its approval of Zepzelca.
IMforte is one of two trials that Jazz is running in place of ATLANTIS, which are in line with its discussions with the FDA. The second study is dubbed LAGOON, which launched in 2022 and will test the approved dose of Zepzelca as a monotherapy, as well as a lower Zepzelca dose combined with irinotecan.
