Jazz Pharmaceuticals’ Zepzelca, once on the brink of a market withdrawal, has returned with new trial results showing it could prolong patients’ lives in extensive-stage small cell lung cancer (ES-SCLC).
Zepzelca, used in combination with Roche’s Tecentriq, outperformed Tecentriq alone when used as a first-line maintenance treatment in ES-SCLC following induction therapy with Tecentriq and chemo, Jazz said Tuesday.
The addition of Zepzelca delayed disease progression and extended survival, leading to a statistically significant improvement in both overall survival and progression-free survival by independent review in the phase 3 IMforte trial. According to Jazz, the combo was generally well-tolerated with no new safety signals.
With the positive results, Jazz plans to file the Zepzelca-Tecentriq combo for an FDA approval in first-line maintenance ES-SCLC in the first half of 2025, the company’s R&D head Rob Iannone, M.D., said in a statement.
It’s quite the turn of event for Zepzelca, a chemotherapy that Jazz licensed from PharmaMar. The alkylating agent got an accelerated approval from the FDA in June 2020 as a single agent for SCLC following previous treatment with platinum-based chemotherapy.
But the phase 3 ATLANTIS trial that could have converted that conditional nod later failed to show an overall survival benefit for Zepzelca’s combination with doxorubicin versus physician’s choice of chemotherapy in second-line SCLC.
Nevertheless, the FDA in 2022 rebuffed a citizen petition to pull Zepzelca from the U.S. market, noting that the use of a lower dose than its approved version might be the culprit behind the trial failure. The agency also cited a lack of treatment options in second-line SCLC.
In the current Roche-sponsored IMforte trial, Zepzelca is being studied at its approved 3.2 mg/m2 dose.
While keeping Zepzelca’s accelerated approval in place, the FDA accepted Jazz’s proposal of two new trials to confirm Zepzelca’s efficacy, and one of them is IMforte. The trial had previously carried a primary completion date in September 2025.
The more relevant study is coded LAGOON. That phase 3 trial is evaluating Zepzelca either by itself at 3.2 mg/m2 per dose, or at 2 mg/m2 in combination with irinotecan, versus physician’s choice of chemo in patients with relapsed SCLC. Started in July 2022, the study bears an estimated primary completion date in April 2026 and is still recruiting patients.
In a statement to Fierce Pharma, Jazz said it’s “premature to confirm” whether the IMforte results will be able to convert Zepzelca’s accelerated approval to a full nod.
The new trial win comes as Zepzelca starts to face competition in the form of Amgen’s first-of-its-kind DLL3-directed bispecific Imdelltra in previously treated ES-SCLC. By cross-trial comparison, Imdelltra’s efficacy appears better than Zepzelca’s on tumor response rate, duration of response and overall survival in their separate single-arm trials.
As to first-line ES-SCLC, Tecentriq, first used in combination with chemotherapy then as a monotherapy in the maintenance phase, has been approved by the FDA since March 2019. Merck & Co.’s bid to improve upon that regimen with a fixed dose combination of its PD-1 inhibitor Keytruda and anti-TIGIT antibody vibostolimab ended in failure in August.