Topotecan Hydrochloride

Breakthrough Second-Line Treatment Demonstrated Survival Advantage over Standard-of-Care Chemotherapy Late-Breaking Data Presented at ASCO 2025 and Simultaneously Published in The New England Journal of Medicine THOUSAND OAKS, Calif. , June 2, 2025 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new interim results from the global Phase 3 DeLLphi-304 trial showing IMDELLTRA ® (tarlatamab-dlle) reduced the risk of death by 40% and significantly extended median overall survival (OS) by more than five months compared to standard-of-care (SOC) chemotherapy in patients with small cell lung cancer (SCLC) who progressed on or after one line of platinum-based chemotherapy (median OS: 13.6 vs 8.3 months; hazard ratio [HR], 0.60; 95% confidence interval [CI]: 0.47, 0.77; P < 0.001). The results will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (LBA8008) and have been published in The New England Journal of Medicine . "Small cell lung cancer is an extraordinarily aggressive and difficult-to-treat disease, and those living with SCLC often experience limited benefit with first line treatment," said Jay Bradner , M.D., executive vice president, Research and Development, at Amgen. "These data underscore IMDELLTRA's potential to transform patient outcomes and the small cell lung cancer treatment paradigm." At the planned interim analysis, DeLLphi-304 met its primary OS endpoint and key secondary progression-free survival (PFS) endpoint. Additionally, IMDELLTRA significantly improved patient-reported outcomes (PRO) for cancer-related symptoms of dyspnea and cough compared to the control arm. "The data from DeLLphi-304 mark a major milestone for people with relapsed small cell lung cancer. Tarlatamab is associated with significant improvements in both overall and progression-free survival over standard chemotherapy in patients with recurrent or progressive disease," said Charles Rudin , M.D., Ph.D., deputy director, Memorial Sloan Kettering Cancer Center . "This study also provides confirmatory data on management of potential toxicities associated with bispecific T-cell engager therapies in a large patient cohort, which is crucial to continuing to improve the experience of patients treated with these medicines." At a median follow-up of 11.2 months for IMDELLTRA and 11.7 months for the control arm, data from the global Phase 3 DeLLphi-304 clinical trial showed a median OS of 13.6 months with IMDELLTRA compared to 8.3 months with local SOC chemotherapy (HR, 0.60; 95% CI: 0.47, 0.77; P < 0.001). Median PFS was statistically significantly improved for IMDELLTRA compared to local SOC chemotherapy (median PFS: 4.2 vs 3.7 months; HR, 0.71; 95% CI: 0.59, 0.86; P < 0.001). The safety profile for IMDELLTRA in DeLLphi-304 was consistent with its known profile. In DeLLphi-304, lower rates of grade 3 or higher treatment-related adverse events (TRAEs) occurred with IMDELLTRA versus the control arm (27% vs 62%) and discontinuations due to TRAEs were lower with IMDELLTRA compared to the control arm (3% vs 6%). The most common grade 3 or greater TRAEs were neutropenia (4%) and lymphopenia (4%) with IMDELLTRA and anemia (28%) and neutropenia (22%) with local SOC chemotherapy.  Cytokine release syndrome (CRS) with IMDELLTRA primarily occurred after receipt of one of the first two doses and was primarily low grade (42% Grade 1; 13% Grade 2; 1% Grade 3) and manageable. No Grade 4 or Grade 5 CRS events were reported. CRS profiles following the first two doses of IMDELLTRA, including incidence, severity, outcome, time to intervention and time to resolution, were similar among patients who were monitored for 6 to 8 hours (n=43) and those who were monitored for 48 hours (n=209). DeLLphi-304 is a global Phase 3, randomized, controlled, open-label clinical trial evaluating the efficacy and safety of IMDELLTRA as a treatment for patients living with SCLC who progressed on or after a single line of platinum-based chemotherapy. 1 Five hundred and nine patients were randomized to receive either IMDELLTRA or local SOC chemotherapy (topotecan in all countries except Japan ; lurbinectedin in the U.S. , Canada , Australia , Singapore , Korea ; and amrubicin in Japan ). 1,2 The primary outcome measure of the trial is OS. 1 Key secondary outcome measures include PFS and PROs including disease-related symptoms, physical function and quality of life. 1 DeLLphi-304 is intended to serve as the confirmatory trial for IMDELLTRA's accelerated approval for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. About IMDELLTRA ® (tarlatamab-dlle) IMDELLTRA is a first-in-class targeted immunotherapy engineered by Amgen researchers to bind to both DLL3 on tumor cells and CD3 on T cells, thereby activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell. 3,4 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target. 5,6 IMDELLTRA ® (tarlatamab-dlle) U.S. Indication IMDELLTRA ® (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). About Small Cell Lung Cancer (SCLC) SCLC is one of the most aggressive and devastating solid tumor malignancies, with a 5-10% five-year relative survival rate across all stages combined. 7 SCLC comprises about 15% of the more than 2.4 million patients diagnosed with lung cancer worldwide each year. 8-10 Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options. 9 About Tarlatamab Clinical Trials Amgen 's robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as a monotherapy and as part of combination regimens, including in both earlier stages of SCLC and earlier lines of treatment. Tarlatamab is being investigated in multiple studies including DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard-of-care therapies in first-line ES-SCLC; DeLLphi-304, a randomized Phase 3 study comparing tarlatamab monotherapy with standard-of-care chemotherapy in second-line treatment of SCLC; DeLLphi-305, a randomized Phase 3 study comparing tarlatamab in combination with durvalumab versus durvalumab alone as first-line maintenance treatment in ES-SCLC;  DeLLphi-306, a randomized placebo-controlled Phase 3 study of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC; DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab in second line or later ES-SCLC; DeLLphi-309, a Phase 2 study evaluating alternative intravenous dosing regimens with tarlatamab in second-line ES-SCLC; DeLLphi-310, a Phase 1b study of tarlatamab in combination with YL201 with or without anti-programmed death ligand 1 (PD-L1) in patients with ES-SCLC; and DeLLphi-312, a Phase 3 study evaluating tarlatamab as an induction and maintenance therapy in first-line treatment of ES-SCLC in combination with carboplatin, etoposide, and durvalumab. 11 For more information, please visit www.tarlatamabclinicaltrials.com . About Amgen Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions . Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average ® , and it is also part of the Nasdaq-100 Index ® , which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit Amgen.com and follow Amgen on X , LinkedIn , Instagram , YouTube and Threads . IMDELLTRA ® (tarlatamab-dlle) Important Safety Information (USPI) WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME WARNINGS AND PRECAUTIONS ADVERSE REACTIONS DOSAGE AND ADMINISTRATION: Important Dosing Information Please see IMDELLTRA ® full Prescribing Information , including BOXED WARNINGS. Amgen Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen . 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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.”