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Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review
Andrea Torchia1,2, Giuliana Ciappina3, Maristella Giammaruco2
1Clinical and Molecular Medicine, Sapienza - Università di Roma, Rome, Italy.
Abstract:
Small-cell lung cancer (SCLC) is the most aggressive lung cancer, mostly diagnosed at advanced stage, and with few therapeutic options for patients failing the first-line treatment. Antibody-based therapies, such as antibody-drug conjugates and T-cell engagers, are emerging as a promising option in the treatment of various solid tumors, including SCLC. T-cell engagers are molecules able to trigger the T-cell-mediated tumor cell death binding, at the same time, a T-cell and a tumor cell target. Tarlatamab is a DLL3-directed bi-specific T-cell engager (BiTE) whose efficacy was evaluated in a Phase 2 study. Antibody-drug conjugates (ADC) consist of a tumor-directed monoclonal antibody conjugated to a cytotoxic payload able to selectively kill tumor cells through different mechanisms. Ifinatamab-deruxtecan is an anti-B7-H3 ADC showing efficacy in pretreated SCLC patients in a phase 2 clinical trial. Sacituzumab govitecan is a Trop-2-directed ADC already used in other tumor types and evaluated in SCLC in the phase 2 TROPiCS-03 trial, with positive results. Bispecific antibodies targeting VEGF and PD-(L)1 showed antitumor activity in phase 1 and 2 clinical trials. Other antibody-based agents are currently at an earlier phase of their clinical development and showed a promising activity. Novel antibody-based agents could potentially acquire a prominent role in the treatment of SCLC, a field with few therapeutic options. Direct comparisons with the current standard of care still lack, however Phase 3 trials are currently ongoing.
Insights
Novel antibody-based therapies, including T-cell engagers and antibody-drug conjugates, show promise for treating advanced small-cell lung cancer (SCLC) where options are limited.
Area of Science:
- Oncology
- Immunotherapy
- Drug Development
Background:
- Small-cell lung cancer (SCLC) is highly aggressive with limited treatment choices for advanced stages.
- Few therapeutic options exist for patients who progress after first-line treatment for SCLC.
- Antibody-based therapies are emerging as a promising avenue for various solid tumors, including SCLC.
Purpose of the Study:
- To review the emerging role of novel antibody-based therapies in treating small-cell lung cancer.
- To highlight promising agents like T-cell engagers and antibody-drug conjugates (ADCs) in SCLC treatment.
- To discuss the potential of these novel agents in a field with unmet therapeutic needs.
Main Methods:
- Review of clinical trial data for antibody-based therapies in SCLC.
- Focus on T-cell engagers (e.g., Tarlatamab) and ADCs (e.g., Ifinatamab-deruxtecan, Sacituzumab govitecan).
- Inclusion of bispecific antibodies targeting VEGF and PD-(L)1, and other early-phase agents.
Main Results:
- Tarlatamab (DLL3-directed T-cell engager) showed efficacy in a Phase 2 study.
- Ifinatamab-deruxtecan (anti-B7-H3 ADC) demonstrated efficacy in pretreated SCLC patients.
- Sacituzumab govitecan (Trop-2-directed ADC) yielded positive results in the TROPiCS-03 trial.
- Bispecific antibodies targeting VEGF and PD-(L)1 exhibited antitumor activity in early trials.
- Other antibody-based agents in earlier development show promising activity.
Conclusions:
- Novel antibody-based agents hold significant potential to become prominent in SCLC treatment.
- These therapies offer new hope in a field with few available treatment options.
- Phase 3 trials are ongoing to further evaluate efficacy and compare with current standards of care.
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