The recent approval of tarlatamab-dlle (Imdelltra; Amgen) for treating solid tumors marks a significant advancement not only in the pharmacy world but also in the oncology space. Tarlatamab’s accelerated approval represents a new potential for transforming solid tumor cancer treatment and offers new hope for these patients beyond traditional therapies such as platinum agents and radiation.
Tarlatamab was granted accelerated FDA approval on May 16, 2024, for the treatment of adult patients with relapsed or refractory extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.1 It is the second bispecific approved for the treatment of solid cancers after tebentafusp (Kimmtrak; Immunocore Holdings plc), which is indicated for uveal melanoma. Tarlatamab is a bispecific T-cell engager (BiTE), which is a specialized form of a traditional bispecific that works by binding a T cell and a cancerous cell. BiTE therapies aim to activate a patient’s T cells to fight specific cancer cells and leverage T-cell toxicity while achieving a highly targeted immune response.1,2 Traditionally, bispecific therapies refer to bispecific antibody therapies that bind to 2 distinct binding sites (ie, molecules or antigens) such as amivantamab, which targets 2 different receptor types to inhibit cancerous growth. Although bispecific antibodies have been a novel therapy option for hematological indications for some time, bispecific T-cell targeting is generally a newer and more promising concept for solid tumor cancers.
Although it may be premature to compare tarlatamab with other first-line therapies for ES-SCLC, the approval of tarlatamab signifies a new era of potentially restructuring traditional standards of care. Currently, tarlatamab is being included in the National Comprehensive Cancer Network’s guidelines as a subsequent treatment option after first-line therapy. The current standard of care for ES-SCLC typically includes platinum-based chemotherapy combined with an immune checkpoint inhibitor.3,4 This regimen has shown improved overall survival compared with chemotherapy alone, but with the rise of new mechanisms such as tarlatamab, we can consider new avenues of treatment for patients whose treatment failed with this therapy. As we await further pharmacovigilance data and a second phase 3 trial, we can position tarlatamab as a second-line or later-line therapy for ES-SCLC for patients with relapsed/refractory disease.1,3,5 This is particularly significant given the limited treatment options historically available for SCLC and relatively conservative developments in the SCLC treatment paradigm in years past.
Overview of ES-SCLC
SCLC is one of the most aggressive solid tumor malignancies, with a median survival of approximately 12 months following initial therapy and a 5-year relative survival rate of 3% for ES-SCLC. Current second- and third-line treatments provide a short duration of response (DOR) and limited survival. Although the initial response rates to first-line platinum-based chemotherapy are high, most patients may experience relapse within months and need further treatment options.3 With the accelerated FDA approval of tarlatamab, patients with ES-SCLC will likely see better outcomes. Based on findings from the phase 2 DeLLphi-301 clinical trial (NCT05060016), it was reported that tarlatamab has a 40% overall response rate, with a median DOR of 9.7 months. In comparison, the median DOR for current second-line therapies is 3.3 to 5.3 months and for third-line chemotherapies is 4.4 to 5.3 months.1
Clinical Trial Success
Specifically, tarlatamab is a BiTE that binds to the DLL3 expressed on the surface of tumor cells and CD3 proteins that are expressed on the surface of a patient’s T cells.1 This dual-targeting approach allows for more precise and effective targeting of cancer cells while minimizing damage to healthy tissues.
Tarlatamab targets DLL3, which is overexpressed in approximately 80% to 90% of patients with SCLC. This widespread expression negates the need for biomarker genetic testing before the initiation of treatment. In the DeLLphi-301 trial findings, an overwhelming majority of patients, approximately 96%, expressed DLL3. Therefore, per the FDA and Amgen, tarlatamab does not require or recommend pretreatment genetic testing for DLL3 expression, which broadens the target population for patients who may benefit from tarlatamab.1,3
Additionally, tarlatamab has been extensively tested in clinical trials in which patients have demonstrated favorable responses with fewer adverse effects (AEs) compared with those typically seen with traditional cancer treatments.5 Similar to other T cell–engaging bispecifics, tarlatamab has boxed warnings for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS). However, tarlatamab has shown reduced incidences of severe (grade 3 or 4) CRS and ICANS. In the pooled safety population, CRS occurred in 55% of patients who received tarlatamab (grade 3, 1.1%; grade 4, 0.5%). The pooled safety population also revealed that neurologic toxicity, including ICANS, occurred in 47% of patients who received tarlatamab-dlle but that only 10% of these patients experienced grade 3 effects. Specifically, ICANS occurred in 9% of tarlatamab-treated patients and recurrent ICANS occurred in 1.6% of patients. In comparison, other bispecific therapies often have rates of CRS or ICANS well over 70% in their patient population.1,3 Moreover, other bispecifics are limited in their administration and may require the institution to both hospitalize the patient and require the institution’s pharmacy to have adequate doses of tocilizumab (Actemra; Genentech), the reversal agent, due to their high incidence of adverse neurological events.
Based on findings from the clinical trials, tarlatamab has a lower risk of infection compared with other treatments. The FDA has not highlighted any required antimicrobial prophylaxis regimens for patients while on tarlatamab, which speaks to tarlatamab’s enhanced safety profile when compared with other bispecific therapies. In the pooled safety population, infections, including opportunistic infections, occurred in only 41% of patients who received tarlatamab, and of those the patients, just 13% had grade 3 or 4 infections. We can appreciate how Amgen’s verbiage on the package insert has left a degree of flexibility for institutions and health care professionals to make individualized clinical decisions based on institutional treatment policies and specific patient characteristics.1 This ultimately can broaden the population eligible to receive treatment with tarlatamab.
Administration of Tarlatamab
Pharmacists play a critical role in the administration of emerging bispecific therapies such as tarlatamab. Pharmacists are quintessential players on an interdisciplinary team because they help to set up initial treatment protocols and institution-specific standard procedures when onboarding new drugs. We expect this to be the case as bispecifics continue to enter the market and change the way traditional chemotherapies are administered. In the case of tarlatamab, step-up dosing is preferred and recommended by its manufacturer. Patients should be monitored in an appropriate health care facility to safely monitor and treat any AEs that can be caused by tarlatamab, such as CRS and ICANS. Although the pivotal clinical trial protocol mandated hospitalization for the initial administration of tarlatamab, the package insert commonly uses the term appropriate health care facility. Institutions have kept the option open for potential outpatient administration, providing flexibility in patient management and increasing the accessibility of this therapy for patients without access to inpatient facilities.1
To determine when it is appropriate to consider tarlatamab, an interprofessional collaboration among the physician, pharmacist, patient, and other health care professionals is essential. Although well-established second-line therapies such as lurbinectedin (Zepzelca; Jazz Pharmaceuticals, PharmaMar), topotecan (Hycamtin; Pfizer), or supportive care are available, tarlatamab offers potential benefits.3,4 Tarlatamab has a lower risk of infection and gastrointestinal AEs and can be administered in an outpatient setting, which enhances convenience and quality of life (QOL) for patients. Although tarlatamab has the potential to cause CRS or ICANS, few patients in the DeLLphi-301 study who experienced grade 3 or 4 CRS or ICANS were treated with appropriate interventions.1 With pharmacists and other health care workers closely monitoring and managing patients on tarlatamab, it is a promising therapy to consider and discuss with the patient.
Accessibility of Treatment
From a health care system perspective, the integration of tarlatamab into treatment protocols could also have significant economic implications. Although novel therapies often come with high price tags, their potential to reduce the need for extended hospital stays and mitigate the costs associated with severe AEs could offer a compelling case for investment. Moreover, the long-term benefits of improved survival rates and reduced recurrence could outweigh initial expenditures.
With the flexibility in administration, pharmacists will also have a critical role in navigating the health care reimbursement and insurance systems for both hospital payers and patients alike. Pharmacists should be well-informed about the costs of administration and insurance reimbursement rates, which unfortunately play a tremendous role in determining which health care centers and patients can afford these novel treatments.
About the Authors
Amir Ali, PharmD, BCOP, is a clinical pharmacist specialist at the University of Southern California (USC) Norris Comprehensive Cancer Center and an adjunct assistant professor of pharmacy practice at USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences in Los Angeles.
Phoebe Kim is a class of 2025 PharmD candidate at the University of Southern California Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences in Los Angeles.
Stacey Cheung is a class of 2025 PharmD candidate at the University of Southern California Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences in Los Angeles.
Samantha Shi, PharmD, BCOP, is a pharmacy manager and the PGY-2 residency director at the University of Southern California Norris Comprehensive Cancer Center in Los Angeles.
Harry Shamamian, PharmD, MBA, FACHE, is the director of pharmacy services at the University of Southern California (USC) Norris Cancer Hospital and Clinics Investigational Drug Service at Keck Medicine of USC in Los Angeles.
Hien Tang, PharmD, BCOP, is a pharmacy manager at the University of Southern California Norris Comprehensive Cancer Center in Los Angeles.
Ultimately, as with any new treatment, the challenge of accessibility remains. Ensuring that tarlatamab is available to all patients who are indicated for therapy, regardless of geographic or economic barriers, will be critical in maximizing its impact. This will require collaboration between health care providers, policy makers, and pharmaceutical companies to develop strategies that address these barriers and ensure health care personnel are well prepared to administer and provide supportive care for patients on therapy. Moreover, continued advocacy for equitable access to cutting-edge therapies will be essential to ensure that advancements in cancer treatment are available for patients who may benefit from them.
Additionally, despite receiving accelerated FDA approval, tarlatamab remains under market surveillance and is actively being studied. As the research unfolds, it will yield valuable insights that may shape its future application and broaden its therapeutic indications. Ongoing monitoring as well as a second phase 3 study will also ensure that its safety and effectiveness are validated across a wider patient demographic and longer period of treatment.3
Considerations for the Future
The approval of tarlatamab is a promising step forward in the treatment of solid tumor cancers that has far-reaching implications. For patients, it brings renewed hope as an additional treatment option with the possibility of fewer AEs and better outcomes. As we have seen and will continue to see, the oncology space is rapidly changing, and as we adopt more therapies using novel mechanisms, such as bispecific targeting, there is significant potential to transform the patient experience, offering a QOL that has often been compromised by more aggressive therapies.
By staying informed about the latest advancements in oncology and by further understanding the unique benefits and administration protocols of new drugs such as tarlatamab, pharmacists can better support oncologists and patients in navigating cancer treatment for aggressive cancers. As we embrace these innovations, ongoing education and collaboration will be essential in optimizing the role of tarlatamab in therapy for multiple indications and ensuring the success of clinical operations in practice.
REFERENCES
1. Imdelltra. Prescribing information. Amgen; 2024. Accessed May 23, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761344s000lbl.pdf
2. Addeo A, Banna GL, Friedlaender A. Tarlatamab: a potential new option for recurrent small cell lung cancer. Transl Lung Cancer Res. 2023;12(7):1628-1630. doi:10.21037/tlcr-23-215
3. FDA approves Imdelltra (tarlatamab-dlle), the first and only T-cell engager therapy for the treatment of extensive-stage small cell lung cancer. News release. Amgen. May 16, 2024. Accessed August 7, 2024. https://www.amgen.com/newsroom/press-releases/2024/05/fda-approves-imdelltra-tarlatamabdllethe-first-and-only-tcell-engager-therapy-for-the-treatment-ofextensivestage-small-cell-lung-cancer
4. NCCN. Clinical Practice Guidelines in Oncology. Small cell lung cancer, version 2.2025. Accessed September 27, 2024. https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf
5. Flaherty C. Tarlatamab monotherapy is safe, active in DLL3+ neuroendocrine prostate cancer. OncLive. July 11, 2023. Accessed August 14, 2024. https://www.onclive.com/view/tarlatamab-monotherapy-is-safe-active-in-dll3-neuroendocrine-prostate-cancer
