As reported on MedPage Today, an experimental immunotherapy called gotistobart helped patients with advanced squamous non-small cell lung cancer (NSCLC) live longer than standard chemotherapy in the phase III PRESERVE-003 trial.
The study included patients whose cancer had worsened after treatment with a PD-(L)1 inhibitor and platinum-based chemotherapy. Median overall survival was 18.5 months for patients who received gotistobart, compared with 10 months for those treated with docetaxel. This represented a 44% lower risk of death with gotistobart.
Rama Balaraman, MD, of the Ocala Oncology Center in Florida, presented the findings at the World Conference on Lung Cancer in Seoul, South Korea.
An analysis also found that patients who had higher levels of gotistobart in their bodies tended to have better overall survival. These findings support the continued study of a treatment schedule consisting of two 10-mg/kg loading doses, followed by 6 mg/kg every three weeks.
Gotistobart could offer a chemotherapy-free option for people with squamous NSCLC who have already received chemotherapy and immunotherapy, Balaraman said. This group has few treatment choices, partly because targetable genetic changes are uncommon and previous studies in heavily treated patients have produced limited results.
After cancer progresses following initial treatment, docetaxel—with or without ramucirumab (Cyramza)—is a commonly used option. However, docetaxel has shown modest results in this setting. Earlier studies have reported response rates of approximately 10.5% to 12.7%, with overall survival ranging from about 8 to 9.4 months.
Gotistobart is an investigational antibody that targets CTLA-4, an immune-system protein. It is designed to reduce regulatory T cells in the area around the tumor. These cells can suppress the immune response against cancer. According to Balaraman, this approach may help the immune system attack tumor cells while limiting some immune-related side effects.
The updated results came from the first stage of the PRESERVE-003 trial. Earlier findings showed a possible survival benefit with gotistobart. At that time, median overall survival had not yet been reached in the gotistobart group, compared with 10 months in the docetaxel group.
Progression-free survival—the time patients lived before their cancer worsened—was similar between the two groups: 2.4 months with gotistobart and 2.6 months with docetaxel. However, the results favored gotistobart overall. The confirmed response rate was 20% with gotistobart, compared with 4.8% with docetaxel.
The first stage of the trial enrolled 217 people with metastatic NSCLC at treatment centers in the United States, Australia, China, South Korea and the United Kingdom between June 2023 and September 2024. Among them, 91 had squamous NSCLC and 126 had non-squamous disease.
Four of the 91 patients with squamous NSCLC initially received gotistobart at 3 mg/kg. That treatment group was later closed following a recommendation from the study’s independent Data Monitoring Committee. The remaining 87 patients received either gotistobart alone—6 mg/kg after two 10-mg/kg loading doses—or docetaxel at 75 mg/m².
There were 45 patients in the gotistobart group and 42 in the docetaxel group. The median age was 64 years among those receiving gotistobart and 68.5 years among those receiving docetaxel. Most participants were men, Asian and former smokers, and about one-quarter were from the United States. All had metastatic disease when they entered the study. Approximately 70% had received one previous systemic treatment, while the remaining patients had received two or more.
Gotistobart does not yet have FDA approval for this use. BioNTech received FDA Fast Track designation for the therapy in 2022 and orphan drug designation in 2025 for its potential use as a second-line treatment for NSCLC.
