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Case Reports
. 2025 Aug;20(8):1131-1138.
doi: 10.1016/j.jtho.2025.02.023. Epub 2025 Mar 24.

Rapid Intracranial Response With Tarlatamab in Patients With Untreated Brain Metastases From SCLC-A Real-World Case Series: Case Report

Bingnan Zhang  1 , Komal B Shah  2 , Mitchell Parma  3 , Kaiwen Wang  4 , Eric K Singhi  1 , Whitney Lewis  4 , Melvin Rivera  4 , Mehmet Altan  1 , Jenny Pozadzides  1 , Xiuning Le  1 , Natalie Vokes  1 , Frank Fossella  1 , Barbara O'Brien  5 , Chenyang Wang  6 , Martin C Tom  6 , Thomas Beckham  6 , Todd Swanson  6 , Julianna Bronk  7 , Steven H Lin  7 , Maria Franco Vega  8 , Joshua Jacome  1 , Alexa Halliday  1 , Marcelo Negrao  1 , Jianjun Zhang  1 , Don L Gibbons  1 , John V Heymach  1 , Lauren A Byers  1 , Carl M Gay  9
Affiliations
Case Reports

Rapid Intracranial Response With Tarlatamab in Patients With Untreated Brain Metastases From SCLC-A Real-World Case Series: Case Report

Bingnan Zhang et al. J Thorac Oncol. 2025 Aug.

Abstract

SCLC has the highest propensity for brain metastases among all malignancies. Systemic treatment for SCLC, particularly in the setting of brain metastases, is very limited. Tarlatamab, the CD3/delta-like ligand 3 bispecific T-cell engager, has changed the treatment landscape of relapsed SCLC since its Food and Drug Administration approval in May 2024. Patients with treated and stable brain metastases were included in the phase 1 DeLLphi-300 trial and phase 2 DeLLphi-301 trials of tarlatamab. Nevertheless, it remains unknown if tarlatamab is safe and efficacious in the setting of untreated, active or symptomatic brain metastases. Our case series provides, to our knowledge, the first reported evidence of the safety and efficacy of tarlatamab in patients with untreated brain metastases. In our cohort of 10 patients with relapsed SCLC and untreated brain metastases, including those with symptomatic intracranial disease and one with suspected leptomeningeal disease, clinical response or stability was seen in 90% of patients. We present several cases in which rapid, dramatic radiographic responses and clinical improvement were observed in patients with innumerable growing brain metastases (>20 lesions) who would otherwise require whole brain radiation, suggesting that tarlatamab can control intracranial metastases as monotherapy, potentially sparing or deferring the need for brain radiation.

Keywords: Case report; Small cell lung cancer; Tarlatamab intracranial efficacy; Untreated brain metastases.

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Conflict of interest statement

Disclosure Dr. B. Zhang reports research support from Lung Cancer Research Foundation and advisory board fees from Abdera Therapeutics. Dr. O’Brien reports participation on advisory board on Plus Therapeutics and leadership role in Society of Neuro-Oncology brain Mets Track Co-chair. Dr. Singhi reports research funding from Rexanna's Foundation for Fighting Lung Cancer; speaking fees from OncLive, Targeted Oncology, MLI education, DAVA Oncology and advisory board on AstraZeneca, Novocure, Amgen, Janssen, Regeneron, Bayer, BMS, BI, Eli Lilly. Dr. Gibbons reports grants from Takeda, NGM Biopharmaceauticals, Boehringer Ingelheim and AstraZeneca; consulting fees from Sanofi, Menarini Ricerche, Onconova, and Eli Lilly. Dr. Heymach reports grants from AstraZeneca, Boehringer-Ingelheim, Mirati, Bristol-Myer Squibb, Takeda, Taiho; consulting fees from AbbVie, Amgen, AnHeart Therapeutics, Arrivent, AstraZeneca, BioNTech AG, BI, BMS, Curio Science, DAVA Oncology, Eli Lily & Co, EMD Serono, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Mirati Therapeutics, Moffitt Cancer Center, ModeX, Novartis Pharmaceuticals, OncoCyte, Pfizer, Sanofi, Spectrum Pharmaceuticals, Takeda; speaking fees from MJH Events, Guidepoint, IDEOlogy. Dr. J. Zhang reports research fundings from National Cancer Institute of the National Institute of Health Research Project Grant (R01CA234629), the AACRJohnson & Johnson Lung Cancer Innovation Science Grant (18-90-52-ZHAN), the MD Anderson Physician Scientist Program, MD Anderson Lung Cancer Moon Shot Program; consulting fees from Johnson and Johnson, AstraZeneca, Novartis; speaking fees from Novartis, Bristol Myers Squibb, AstraZeneca, GenePlus, Innovent, and Hengrui; advisory board from Novartis, AstraZeneca, GenePlus, Catalyst. Dr. Byers reports grant contracts from Circle Pharma, Amgen; consulting fees from Merck, Arrowhead Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Genetech, BeiGene, AbbVie, Jazz Pharmaceuticals, Puma Biotechnology, Amgen, Daiichi Sankyo, and Novatis. Boehringer Ingelheim. Dr. Gay reports consulting fees from Abdera, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, G1, Jazz, Monte Rosa, OncoHost, and Roche/Genentech; speaking fees from ACHL, AstraZeneca, BeiGene, Daiichi Sankyo, IDEOlogy, IDR, MJH, OncLive, PeerView, PER, Targeted Healthcare, Catalyst, Kisoji, and STCube. The remaining authors declare no conflict of interest.

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