BALTIMORE, June 19, 2025 – A panel of experts from the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center discussed evolving treatment strategies for extensive-stage small cell lung cancer (ES-SCLC). The discussion, part of an “Around the Practice: Institutional Insights” program, highlighted tarlatamab-dlle (Imdelltra) as a promising new agent.
Tarlatamab, a DLL3-targeting agent, shows promise in treating ES-SCLC, but comes with side effects like ICANS and CRS.
- Tarlatamab is a DLL3-targeting agent showing encouraging activity in ES-SCLC.
- The drug has shown a 40% response rate in heavily pretreated patients.
- Adverse effects include immune effector cell–associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS).
Tarlatamab is emerging as a noteworthy option, especially given its ability to target DLL3, a protein commonly found in these cancers. The panel, led by Dr. Samuel Rosner, also addressed the adverse effects associated with tarlatamab, including immune effector cell–associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS).
The panel included Samuel Rosner, MD, Ranee Mehra, MD, Michelle Sittig, RN, OCN, and Kaitlyn Whyman, DNP, CRNP, AGACNP-BC.
Current Treatment Landscape
Dr. Mehra explained that the frontline treatment for ES-SCLC has largely been shaped by two trials. Both studies used immune checkpoint inhibitors with platinum therapy and etoposide. The IMpower133 trial incorporated atezolizumab (Tecentriq), and the CASPIAN study used durvalumab (Imfinzi), both followed by maintenance therapy. These studies showed improved overall survival with the addition of an immune checkpoint inhibitor.
Previously, patients would undergo six cycles of chemotherapy, followed by a treatment break, often leading to rapid progression. Now, more effective and well-tolerated treatment options are available, resulting in better quality of life and longer survival. However, progression remains a challenge.
Dr. Rosner then asked about factors and treatment options available for patients in the second-line setting, after the initial treatment.
Dr. Mehra noted that in the second-line setting, topotecan (Hycamtin) has historically been used. More recently, lurbinectedin (Zepzelca) has also become a treatment option. While lurbinectedin has shown survival benefits, it also carries significant toxicity.
New Directions in ES-SCLC Trials
Dr. Rosner inquired about recent developments in the second-line ES-SCLC setting.
Dr. Mehra discussed several interesting trials. The IMforte trial is evaluating the addition of lurbinectedin to maintenance therapy with atezolizumab. After standard induction treatment with platinum, etoposide, and atezolizumab, patients are randomly assigned to either continue standard therapy or receive additional lurbinectedin. The results of this trial are pending. Another approach involves incorporating tarlatamab earlier in the frontline treatment setting.
The DeLLphi-301 study was key in incorporating tarlatamab. This study enrolled heavily pretreated patients; about a third had received at least three prior lines of therapy, and 70% to 80% had previously used an immune checkpoint inhibitor. In this population, which had progressed on standard options, tarlatamab showed promising activity. Response rates were 40%, and median overall survival improved to 15 months.
Dr. Mehra stated that performance status and the presence of brain metastases were crucial factors in making treatment decisions for patients who have progressed on chemoimmunotherapy. Tarlatamab can be active in the brain, which may not be true for other cytotoxic agents.
Implementing Tarlatamab: Protocols and Challenges
Dr. Rosner inquired about the protocol for initiating tarlatamab and collaborating with community partners.
Michelle Sittig explained that initiating tarlatamab required significant coordination, involving administration, pharmacy, and both inpatient and outpatient clinics. Once established, the program has been successful, with patients now transitioning back to the community. The community needs time to set up their sites, often modeling their processes after the center’s practices.
Dr. Rosner asked about the challenges of starting patients and transitioning them to the outpatient setting.
Sittig emphasized the importance of clear communication with patients to ensure they fully understand the treatment. The inpatient dosing is challenging due to significant adverse effects. Patients need a solid understanding of the dosing regimen of every two weeks, indefinitely. Efforts are focused on ensuring patients, families, and caregivers understand the intensity of the regimen.
Dr. Rosner then asked about logistical considerations for other institutions.
Kaitlyn Whyman noted the importance of following protocols and standardization. They have learned not to use a one-size-fits-all model. Monitoring for 24 to 48 hours is important. However, much can be gleaned about how a patient will react to the second dose after the first. The team monitors for specific adverse effects and adjusts accordingly.
Dr. Rosner asked about coordinating care, especially in the inpatient setting.
Whyman highlighted the crucial role of pharmacists in building plans and protocols. As a provider, she stays connected with pharmacists and nurses, who are experiencing a significant practice change. These new drugs require different monitoring protocols. Ensuring that everyone is comfortable with the protocols is key.
Managing Adverse Effects
Dr. Rosner asked about the symptoms observed and how they are managed.
Whyman noted that initial confusion is a common early symptom. General ICANS assessments include questions about orientation. Subtle issues with dexterity and fine motor movements are also observed. Patients may struggle to write their name or use utensils.
The standard of care involves treatment with dexamethasone. Dexamethasone is efficient in controlling symptoms. Many patients experience resolution after one or two doses. While concerning, early intervention makes management easier.
Neurology is consulted when needed, and levetiracetam (Keppra) may be started if there is a risk of seizures.
Dr. Rosner asked about the signs, speed of onset, and management of CRS.
Whyman observed that CRS typically appears later, around 12 to 24 hours after treatment. Early signs often include a fever or an elevated heart rate. Depending on the severity, patients may experience hypotension and chills.
The treatment approach is determined by the overall picture. Tocilizumab (Actemra) may be administered if the condition is severe. White blood cell counts and potential infections are also considered.
Dr. Rosner suggested involving the critical care team if patients develop hypertension.
Sittig provides the manufacturer’s brochure, which outlines observation times. Outpatient observation times range from eight hours initially, reducing to two hours by cycle five. The brochure includes CRS information. It’s important to stress that the first two doses can be the hardest, and the patient’s condition often improves.
References
- Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N engl j with. 2018; 379 (23): 2220-2229. DOI: 10.1056/NEJMO1809064
- Goldman JW, Dvorkin M, Chen Y, et al; CASPIAN Investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021; 22 (1): 51-65. Two: 10.1016/S1470-2045 (20) 30539-8
- Manzo A, Sforza V, Carillio G, et al. Lurbinectedin in small cell lung cancer. Front Oncol. 2022; 12: 932105. Two: 10.3389/FONC.2022.932105
- Ahn MJ, Cho BC, Felip E, et al; DeLLphi-301 Investigators. Tarlatamab for patients with previously treated small-cell lung cancer. N engl j with. 2023; 389 (22): 2063-2075. two: 10.1056/Nejmoa2307980
