Oncology Insights: Transformative treatment for small cell lung cancer

After decades of research, a new treatment is emerging for this aggressive form of lung cancer

June 19, 2024

Oncology Insights

Transformative treatment for small cell lung cancer

On May 16, the U.S. Food and Drug Administration (FDA) granted accelerated approval to intravenous Imdelltra (tarlatamab) for the treatment of adults with relapsed/refractory extensive stage small cell lung cancer (RR ES-SCLC) with disease progression on or after platinum-based chemotherapy.1 Tarlatamab is an immunotherapy drug that may be administered in the outpatient setting.2  This novel delta-like ligand 3 (DLL3)-targeting bispecific T-cell engager (BiTE) therapy activates the patient’s own T cells to attack DLL3-expressing tumor cells.

The FDA approval was supported by the Phase 2 DeLLphi-301 trial which evaluated 99 patients with RR ES-SCLC after platinum-based chemotherapy.1,2 Efficacy endpoints were overall response rate (40%; 2% complete response; 38% partial responses) and median duration of response (9.7 months; range, 2.7, 20.7+).3,4 Among responders, 68% had a response lasting at least 6 months and 40% had a response lasting at least 12 months.2 Biomarker testing for DLL3 is not required to initiate tarlatamab.5

About 30,000 Americans are diagnosed with small cell lung cancer each year and 85% of these cases overexpress DLL3. 4,7,8 Nearly 60% of all cases are metastatic at diagnosis and cigarette smoking is the cause of nearly all SCLC cases.6 Unfortunately, less than 3% of patients with ES-SCLC live longer than five years.6 Current systemic therapy options such as chemotherapy and checkpoint inhibitors like Keytruda® (pembrolizumab) add about two months to a patient’s life.8 However, treatment resistance and progression are common.4

After decades of research, tarlatamab has emerged as a potential significant change for the treatment of this aggressive form of lung cancer because of improved outcomes compared to current therapy options that follow platinum-based chemotherapy.4 Currently, the National Comprehensive Cancer Network (NCCN) guidelines lists tarlatamab as a category 2A recommendation.8

Boxed warnings include cytokine release syndrome (grade 3 or 4, 1.6%) and neurologic toxicities (grade 3 or 4, 0%).2 Common side effects are fatigue, decreased appetite, low sodium and white blood cell counts.

The first cycle of tarlatamab is administered as step-up dosing to decrease the potential for cytokine release syndrome, then treatment is continued until disease progression or lack of tolerability.4

The wholesale acquisition cost (WAC) of tarlatamab is $31,500 for the first cycle and $30,000 for subsequent cycles for a total annual WAC of $391,500.5 In the DeLLphi-301 trial the median therapy duration was 5.5 months, which would equate to a WAC of about $179,000.

Treatment options for SCLC are limited, so continued advancements are needed. Tarlatamab provides clinical improvements not seen with current therapies. However, it follows the current high-cost trend seen with new to market agents. As additional drugs with improved outcomes are approved, this moves us closer to the possibility of extended disease control and improved outcomes for this aggressive cancer.

References
  1. US Food and Drug Administration. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. Retrieved June 10, 2024 from https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer.
  2. Imdelltra [package insert]. Thousand Oaks, CA; Amgen; May 2024.
  3. ESMO Oncology News. Tarlatamab Shows Promise in Patients with Previously Treated Small-Cell Lung Cancer. Findings from the DeLLphi-301 study. Retrieved June 11, 2024 from https://www.esmo.org/oncology-news/tarlatamab-shows-promise-in-patients-with-previously-treated-small-cell-lung-cancer.
  4. Ahn MJ, Cho BC, Felip E, et al. DeLLphi-301 Investigators. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 30;389(22):2063-2075. doi: 10.1056/NEJMoa2307980. Retrieved June 11 from https://www.nejm.org/doi/10.1056/NEJMoa2307980?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.
  5. IPD Analytics. New Drug Review. Imdelltra (tarlatamab-dlle). May 2024.
  6. Basumallik N, Agarwal M. Small Cell Lung Cancer. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Retrieved June 11, 2024 from https://www.ncbi.nlm.nih.gov/books/NBK482458/.
  7. Bylsma LC, Pundole X, Ju CH, et al. Systematic Literature Review of the Prevalence and Prognostic Value of Delta-Like Ligand 3 Protein Expression in Small Cell Lung Cancer. Target Oncol. 2023 Nov;18(6):821-835. doi: 10.1007/s11523-023-01008-x.
  8. Ganti AKP, Loo BW, Bassetti M, et al. National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology. Small Cell Lung Cancer. V 3.2024 – June 11, 2024. Retrieved June 11, 2024 from https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf.

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