Tarlatamab Delivered an Encouraging Objective Response Rate of 40% and Median Overall Survival of 14.3 Months in Patients with Advanced SCLC
Late-Breaking Data Presented at ESMO and Published in the New England Journal of Medicine (NEJM)
Tarlatamab is an Investigational Delta-Like Ligand 3 (DLL3) Targeting BiTE® Molecule
THOUSAND OAKS, Calif., Oct. 20, 2023 /PRNewswire/ — Amgen (NASDAQ:AMGN) today announced results from the global Phase 2 DeLLphi-301 study, evaluating tarlatamab, an investigational delta-like ligand 3 (DLL3) targeting BiTE® (bispecific T-cell engager) molecule, in patients with advanced stage small cell lung cancer (SCLC) who had failed two or more prior lines of treatment. The data are being presented today at 3:20 PM CEST at a Proffered Paper session as a late-breaking oral presentation (LBA92) during the European Society for Medical Oncology (ESMO) Congress 2023 in Madrid, Spain, with publication in the New England Journal of Medicine.
With a median follow-up of 10.6 months, an intention-to-treat analysis that included 100 patients at the selected 10 mg dose for tarlatamab demonstrated an objective response rate (ORR; primary endpoint) of 40% (97.5% Confidence Interval (CI): 29, 52). For key secondary endpoints, median progression-free survival (mPFS) was 4.9 months (95% CI: 2.9, 6.7) and median overall survival (mOS) was 14.3 months (95% CI: 10.8, NE). Median response duration was not reached. Of the patients who responded to treatment with tarlatamab at 10 mg dose, 58% experienced at least six months of response and 55% of responses were ongoing at data cutoff.
“Small cell lung cancer has represented one of the greatest challenges in cancer treatment, where there has been little progress against this deadly tumor type in decades,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “The tarlatamab results show the potential for this BiTE® molecule in a common solid tumor. We look forward to discussing these potentially registrational data with regulatory authorities.”
There were no new safety signals observed compared to Phase 1 study. Discontinuations due to treatment-related adverse events (TRAEs) were infrequent (4%). The most common treatment-emergent adverse events (TEAEs) reported among patients in the tarlatamab 10 mg group, were cytokine release syndrome (CRS; 49%), pyrexia (38%), decreased appetite (25%) and dysgeusia (24%). CRS was largely confined to the first and second dose, predominantly grade 1 or 2 and were generally managed with supportive care. At the tarlatamab 10 mg dose, grade 3 CRS was low (0%) and grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurologic events were not observed (0%). There were no reported grade 4 or 5 cases for either of these two adverse events.
“In the current third-line treatment of SCLC, patients face a dire prognosis, with response rates ranging between 14 and 21 percent and median overall survival less than six months,” said Luis Paz-Ares, M.D., Ph.D., chairman, Medical Oncology Department, Hospital Doce de Octubre; Head, Lung Cancer Unit, National Oncology Research Center (CNIO); associate professor, Universidad Complutense.
About Tarlatamab
Tarlatamab is an investigational, targeted immunotherapy engineered by Amgen researchers that brings a patient’s own T cells in close proximity to SCLC cells by binding both CD3 on T cells and DLL3 on SCLC cells. This results in the formation of an immunological synapse with lysis of the cancer cell.1,2 DLL3 represents an exciting therapeutic target for patients with SCLC, as approximately 85% to 94% of patients have expression of DLL3 on the cell surface of SCLC cells, with minimal expression in normal cells.3,4,5
In a Phase 1 study, tarlatamab showed responses in 23.0% of patients with encouraging durability in heavily pre-treated patients with SCLC.
Amgen is currently investigating tarlatamab in multiple trials, including DeLLphi-304, a Phase 3 study comparing tarlatamab versus standard of care chemotherapy in second-line treatment of SCLC that is enrolling patients. Amgen has plans to initiate two additional Phase 3 studies of tarlatamab in earlier settings of SCLC.
About Small Cell Lung Cancer (SCLC)
SCLC is one of the most aggressive and devastating solid tumors with a median survival of approximately 12 months following initial therapy and a 7% five-year relative survival rate across all stages 6,7,8 Of the 2.2M+ patients diagnosed with lung cancer worldwide each year, SCLC comprises 15% of cases.9,10
Despite initial high response rates to platinum-based first-line chemotherapy, patients quickly develop resistance to second-line and subsequent therapies and face a median time of survival of 10 to 12 months after diagnosis.11 Furthermore, there are currently no approved therapeutic options in the third-line treatment of SCLC.
About Tarlatamab Clinical TrialsAmgen’s robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as a monotherapy and as part of combination regimens in earlier stages of SCLC.
Tarlatamab is being investigated in multiple studies, including DeLLphi-301, a potentially registrational Phase 2 study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of tarlatamab in third-line or later relapsed/refractory SCLC.
Additional clinical studies underway include DeLLphi-302, a Phase 1b combination study evaluating tarlatamab in combination with an anti-PD-1 therapy in second-line or later SCLC; DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard of care therapies in first-line SCLC; and DeLLphi-304, a randomized Phase 3 trial comparing tarlatamab monotherapy with standard of care therapy in patients with SCLC who have relapsed following first-line platinum-based chemotherapy.12 Amgen also plans to initiate two additional Phase 3 studies of tarlatamab in earlier settings of SCLC.
For more information, please visit tarlatamab clinical trials.
About BiTE® TechnologyBiTE® (bispecific T-cell engager) technology is a targeted immuno-oncology platform that is designed to engage patient’s own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit https://www.amgenoncology.com/bite-platform.html.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2023, Amgen was named one of “America’s Greatest Workplaces” by Newsweek, one of “America’s Climate Leaders” by USA Today and one of the “World’s Best Companies” by TIME.
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1 Paz-Ares L, et al. J Clin Oncol. 2023. DOI:10.1200/JCO.22.02823. |
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2 Giffin MJ, et al. Clin Cancer Res. 2021;27:1526-1537. |
|
3 Rojo F, et al. Lung Cancer. 2020;147:237-243. |
|
4 Saunders LR, et al. Sci Transl Med. 2015;7:302ra136. |
|
5 Paz-Ares L, et al. J Clin Oncol. 2023;41:2893-2903. |
|
6 American Cancer Society. Lung Cancer Survival Rates. 2023. Available at: https://www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/survival-rates.html. Accessed on October 11, 2023. |
|
7 Paz-Ares L, et al. ESMO Open. 2022;7:100408. |
|
8 Liu SV, et al. J Clin Oncol. 2021;39:619-630. |
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9 World Health Organization. Lung. 2020. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed on October 11, 2023. |
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10 Oronsky B, et al. J Cancer. 2022;13:2945-2953. |
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11 Rudin CM, et al. J Clin Oncol. 2015; 33:4106-4111. |
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12 ClinicalTrials.gov. DeLLphi-304. 2023. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05740566. Accessed on October 11, 2023. |
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