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For Roche, adding Zepzelca as a combination partner could help shore up Tecentriq in first-line ES-SCLC in its competition with AstraZeneca’s Imfinzi. Roche’s plan to bolster Tecentriq’s position in small cell lung cancer with Jazz Pharmaceuticals’ Zepzelca has paid off. But the pair’s success leaves room for improvement for future contenders.Adding Zepzelca on top of Tecentriq as maintenance treatment of first-line extensive-stage small cell lung cancer (ES-SCLC) significantly reduced patients’ risk of death by 27% compared with Tecentriq alone, according to data from the phase 3 IMforte trial.Patients who received the combo lived a median 13.2 months, versus 10.6 for those who got Tecentriq alone. The results will be presented at the 2025 American Society of Clinical Oncology annual meeting.Besides hitting its overall survival goal, IMforte also showed that by taking Zepzelca, patients 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 in the Tecentriq-alone arm.For Roche, adding Zepzelca as a combination partner could help shore up Tecentriq in first-line ES-SCLC in its competition with AstraZeneca’s Imfinzi. For Jazz, the phase 3 win could move Zepzelca from the post-chemo setting to first-line treatment and maybe also turn the drug’s accelerated approval into a full nod.But as ASCO Chief Medical Officer Julie Gralow, M.D., remarked during a press briefing, there’s still room for improvement.“While this is a next step, progression-free survival is still quite low in both arms, and we need to work on additional ways of advancing this even further,” she said. And a better therapy is desired not just on the efficacy side. The addition of Zepzelca during the maintenance phase more than doubled the rate of treatment-related adverse events to 83.5%, compared with 40% in the control group. The rate of grade 3 or 4 adverse events was also notably higher, at 25.6% for the combo, versus 5.8% for Tecentriq alone. But most adverse events were manageable, which is “one of the reasons that Zepzelca was a really good choice for a maintenance regimen,” Jazz’s R&D head, Rob Iannone, M.D., said in an interview with Fierce Pharma.Adverse events led 6.2% of patients in the experimental arm to discontinue treatment, versus 3.3% in the control arm. Iannone described the rate as “very low.” The Zepzelca arm also saw marginally more frequent treatment-related deaths, at 0.8% versus 0.4%, respectively.For existing first-line ES-SCLC regimens involving Tecentriq or Imfinzi, patients receive chemotherapies only during the induction phase because continued dosing in the maintenance phase turned out to be detrimental due to toxicities, Iannone noted.But once that chemo is taken off, there’s a notable worsening of progression curves. That’s why Jazz and Roche figured patients still need another active therapy that’s better tolerated than traditional chemo that can be given as maintenance treatment, Iannone explained.However, as Gralow pointed out, Zepzelca, as a DNA transcription inhibitor, is still a type of chemotherapy, albeit a safer one.More novel agents are emerging. The DLL3 drug class, led by Amgen’s bispecific Imdelltra, has attracted much enthusiasm—including recently from Roche—for its potential in SCLC. Last year, Amgen launched the phase 3 DeLLphi-305 trial adding Imdelltra to Imfinzi as first-line maintenance treatment of ES-SCLC, with an estimated primary completion date in July 2027.Imdelltra’s future looks promising after Amgen recently reported a positive readout in a phase 3 trial in second-line SCLC. It marked the first overall survival win for a T-cell engager in a solid tumor.  At least for now, Zepzelca is the first one to have a positive phase 3 readout in this disease setting, and Iannone argued that the results are practice-changing and serve as a new paradigm for future drugs in the space. Jazz has submitted the IMforte results to the FDA, which has yet to set a target decision date, according to Iannone.IMforte is one of two phase 3 trials that the FDA has agreed could potentially confirm Zepzelca’s clinical benefit after a lower dose of the drug failed to move the needle against chemo in second-line SCLC in the phase 3 Atlantis study. IMforte was sponsored by Roche.The other phase 3 trial that the FDA said could give Zepzelca a traditional approval, Lagoon, finished enrollment in December and could read out topline data in the first quarter of 2026, according to PharmaMar. The three-arm trial evaluates Zepzelca either as monotherapy or in combination with irinotecan against the physician’s choice of topotecan or irinotecan.Jazz in-licensed U.S. rights to Zepzelca from PharmaMar in 2019 by paying $200 million upfront and committing up to $800 million in potential milestones.Jazz has a good track record in licensing cancer drugs. The company’s HER2-targeted bispecific Ziihera, licensed from Zymeworks, recently won FDA approval in HER2-positive biliary tract cancer and is moving toward gastric cancer and breast cancer.After CEO Bruce Cozadd highlighted the company’s continued interest in dealmaking, Jazz agreed to buy Chimerix for $935 million to get hold of dordaviprone, a near-approval small molecule being evaluated by the FDA in recurrent H3 K27M-mutant diffuse glioma.As to Jazz’s future business development plan in oncology, Iannone said: “We are agnostic to modality, again, focused on drugs that will make a meaningful difference for patients, where Jazz really has the capability to develop and commercialize.”