Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review

Andrea Torchia,1,2,* Giuliana Ciappina,3,* Maristella Giammaruco,2 Ilaria Monteferrante,4 Lorenza Landi,5 Federico Cappuzzo2 1Clinical and Molecular Medicine, Sapienza - Università di Roma, Rome, Italy; 2Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy; 3...

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Main Authors: Torchia A, Ciappina G, Giammaruco M, Monteferrante I, Landi L, Cappuzzo F
Format: Article
Language:English
Published: Dove Medical Press 2025-04-01
Series:Biologics: Targets & Therapy
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Online Access:https://www.dovepress.com/antibody-based-therapeutics-in-small-cell-lung-cancer-a-narrative-revi-peer-reviewed-fulltext-article-BTT
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author Torchia A
Ciappina G
Giammaruco M
Monteferrante I
Landi L
Cappuzzo F
author_facet Torchia A
Ciappina G
Giammaruco M
Monteferrante I
Landi L
Cappuzzo F
author_sort Torchia A
collection DOAJ
description Andrea Torchia,1,2,* Giuliana Ciappina,3,* Maristella Giammaruco,2 Ilaria Monteferrante,4 Lorenza Landi,5 Federico Cappuzzo2 1Clinical and Molecular Medicine, Sapienza - Università di Roma, Rome, Italy; 2Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy; 3Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 4Department of Anesthesiology, Intensive Care and Pain Therapy, IRCCS Regina Elena National Cancer Institute, Rome, Italy; 5Clinical Trials Unit: Phase 1 and Precision Medicine, IRCCS Regina Elena National Cancer Institute, Rome, Italy*These authors contributed equally to this workCorrespondence: Federico Cappuzzo, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, 00144, Italy, Email f.cappuzzo@gmail.com, federico.cappuzzo@ifo.itAbstract: 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.Keywords: small-cell lung cancer, treatment, antibody, antibody–drug conjugate, T-cell engager, bispecific antibody
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spelling doaj-art-3e7ece5b76e74bbb936eb241344fb9482025-08-20T02:12:46ZengDove Medical PressBiologics: Targets & Therapy1177-54912025-04-01Volume 19189199102126Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative ReviewTorchia ACiappina GGiammaruco MMonteferrante ILandi LCappuzzo FAndrea Torchia,1,2,* Giuliana Ciappina,3,* Maristella Giammaruco,2 Ilaria Monteferrante,4 Lorenza Landi,5 Federico Cappuzzo2 1Clinical and Molecular Medicine, Sapienza - Università di Roma, Rome, Italy; 2Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy; 3Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; 4Department of Anesthesiology, Intensive Care and Pain Therapy, IRCCS Regina Elena National Cancer Institute, Rome, Italy; 5Clinical Trials Unit: Phase 1 and Precision Medicine, IRCCS Regina Elena National Cancer Institute, Rome, Italy*These authors contributed equally to this workCorrespondence: Federico Cappuzzo, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, 00144, Italy, Email f.cappuzzo@gmail.com, federico.cappuzzo@ifo.itAbstract: 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.Keywords: small-cell lung cancer, treatment, antibody, antibody–drug conjugate, T-cell engager, bispecific antibodyhttps://www.dovepress.com/antibody-based-therapeutics-in-small-cell-lung-cancer-a-narrative-revi-peer-reviewed-fulltext-article-BTTsmall-cell lung cancertreatmentantibodyantibody-drug conjugatet-cell engagerbispecific antibody
spellingShingle Torchia A
Ciappina G
Giammaruco M
Monteferrante I
Landi L
Cappuzzo F
Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review
Biologics: Targets & Therapy
small-cell lung cancer
treatment
antibody
antibody-drug conjugate
t-cell engager
bispecific antibody
title Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review
title_full Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review
title_fullStr Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review
title_full_unstemmed Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review
title_short Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review
title_sort antibody based therapeutics in small cell lung cancer a narrative review
topic small-cell lung cancer
treatment
antibody
antibody-drug conjugate
t-cell engager
bispecific antibody
url https://www.dovepress.com/antibody-based-therapeutics-in-small-cell-lung-cancer-a-narrative-revi-peer-reviewed-fulltext-article-BTT
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AT monteferrantei antibodybasedtherapeuticsinsmallcelllungcanceranarrativereview
AT landil antibodybasedtherapeuticsinsmallcelllungcanceranarrativereview
AT cappuzzof antibodybasedtherapeuticsinsmallcelllungcanceranarrativereview