Exploring the Mechanisms of Action, Efficacy, Outcomes, and Future Potential of Bispecific T-Cell Engager Therapy in Advanced Small Cell Lung Cancer

Opinion
Video

Ticiana Leal, MD, discusses how tarlatamab, a bispecific T-cell engager (BiTE), leverages the aberrant expression of delta-like ligand 3 on small cell lung cancer (SCLC) cells to direct T-cell-mediated tumor lysis, its promising efficacy shown in the phase 2 DeLLphi-301 study, and the potential clinical benefits of combining it with durvalumab for maintenance therapy after platinum-based chemotherapy.

Video content above is prompted by the following:

  1. Please discuss the unique mechanism of action of tarlatamab, a BiTE, and its treatment potential as subsequent therapy for SCLC, which has progressed after platinum-based chemotherapy.
  2. Please provide your insights on an objective response rate (ORR) of 32% to 40% among participants in the 10 mg and 100 mg groups of the DeLLPhi-301 clinical trial.
    1. How clinically meaningful is an OR observed between 5 and 7 weeks of tarlatamab initiation?
  3. What are your views on selecting ORR as the primary
    end point in this study?
  4. Regarding the relatively small number of CR and PR responders (n=68) in DeLLphi-301, what is your opinion about the duration of response to tarlatamab at 6 months or longer (59%), at greater than 9 months (29%), and the ongoing response at data cutoff (>50% [n=38]) in the 2 treatment groups?
  5. What progression-free survival and overall survival end points would you typically expect from second- or third-line therapy in your previously treated patients with relapsed or refractory SCLC?
  6. In your opinion, what is the future treatment potential of tarlatamab as combination therapy with other anticancer agents for previously treated SCLC that has advanced after 2 or more lines of prior therapy?
  7. What additional clinical benefits might we anticipate for patients with ES-SCLC by adding tarlatamab to durvalumab as maintenance therapy after primary treatment with platinum-based chemotherapy plus etoposide plus durvalumab?
    1. What statistically significant trial end points might persuade community oncologists to consider dual maintenance with a bispecific T-cell engager and a PD-L1 inhibitor?
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