Gotistobart Reduces Death Risk in Advanced Squamous NSCLC

Gotistobart reduced the risk of death by 54% and doubled 12-month survival compared with chemotherapy in previously treated advanced squamous non-small cell lung cancer (NSCLC), according to results from the PRESERVE-003 trial.

Findings from stage 1 of the PRESERVE-003 phase 3 clinical trial, published in Nature Medicine, demonstrated that the investigational immunotherapy may improve survival outcomes for patients with metastatic NSCLC, particularly those with squamous histology whose disease has progressed after prior treatment.

The global study included participation from Florida Cancer Specialists & Research Institute and evaluated the efficacy and safety of gotistobart compared with docetaxel in patients who had previously received treatment. Results showed a clinically meaningful survival benefit with gotistobart, suggesting it could represent a potential new treatment option in a setting where outcomes remain limited.

In addition to improving overall survival, gotistobart was associated with a manageable safety profile, supporting its continued investigation in this patient population.

Main data that support the findings

Among patients with squamous NSCLC (sqNSCLC), gotistobart demonstrated a clinically meaningful improvement in overall survival, which was the primary endpoint of the study. Treatment with gotistobart led to a 54% reduction in the risk of death compared with docetaxel (Taxotere). At a median follow-up of 14.5 months, median overall survival was not reached in the gotistobart group, while it was 10 months in the docetaxel group.

The separation in survival outcomes became evident after 6 months and continued throughout the observation period. At 12 months, 63.1% of patients treated with gotistobart were alive, compared with 30.3% of those who received docetaxel, representing a doubling of the survival rate.

Secondary outcomes also supported the potential benefit of gotistobart. The confirmed overall response rate was 20% with gotistobart versus 4.8% with docetaxel. Responses to gotistobart also lasted longer, with a median duration of response of 11 months compared with 3.8 months for docetaxel. Additionally, 15.6% of patients receiving gotistobart remained on treatment for at least 12 months.

Progression-free survival was similar between the two groups, with a median of 2.4 months for gotistobart and 2.6 months for docetaxel, although a trend toward improvement with gotistobart was observed.

In contrast, outcomes for patients with non-squamous NSCLC were numerically better in the docetaxel group. Based on these findings, the study’s data monitoring committee recommended pausing development of gotistobart in patients with non-squamous disease. Additionally, a lower-dose cohort of gotistobart was discontinued after early results showed poor outcomes.

Trial details of PRESERVE-003

The global PRESERVE-003 trial is a multi-year study comparing gotistobart, a CTLA-4 checkpoint-targeting immunotherapy, with docetaxel in patients with advanced NSCLC whose cancer has worsened after prior immunotherapy and chemotherapy.

Stage 1 of the trial enrolled patients between June 2023 and September 2024 across study centers in the United States, Australia, China, Korea and the United Kingdom. Patients were randomly assigned to receive either gotistobart or docetaxel.

The primary goal of this stage was to confirm the appropriate dose of gotistobart and evaluate its early effectiveness and safety. The main outcome measured was overall survival, with additional outcomes including progression-free survival, overall response rate and duration of response.

Following these initial findings, the trial has moved into a later stage to confirm the results in a larger population of patients with squamous NSCLC.

Safety

Side effects were common in both treatment groups. All patients receiving gotistobart experienced at least one side effect of any grade, compared with 97.6% of patients treated with docetaxel. Rates of severe side effects (grade 3 [severe] or higher) were similar between groups, occurring in 66.7% of patients in the gotistobart group and 63.4% in the docetaxel group.

Treatment-related side effects occurred in 84.4% of patients receiving gotistobart and 90.2% of those receiving docetaxel. Severe treatment-related side effects were reported in 42.2% and 48.8% of patients, respectively.

The most common treatment-related side effects with gotistobart were diarrhea and increased alanine aminotransferase levels, each affecting 28.9% of patients. For docetaxel, the most frequent side effects were anemia, reported in 36.6% of patients, and decreased neutrophil count, reported in 24.4%.

Serious immune-related side effects were more frequent with gotistobart, occurring in 60% of patients compared with 9.8% in the docetaxel group. Severe immune-related side effects occurred in 33.3% of patients receiving gotistobart and 4.9% of those receiving docetaxel. Many patients experiencing these side effects required steroid treatment.

Discontinuation due to side effects occurred in 22.2% of patients treated with gotistobart and 4.9% of those receiving docetaxel. No fatal treatment-related side effects were reported. Two deaths occurred in the gotistobart group due to hemoptysis and pneumonia, but investigators determined these were not related to the treatment.

References

1. “Florida Cancer Specialists & Research Institute Phase 3 Trial Demonstrates Initial Clinical Benefit of Novel Immunotherapy For Advanced Non-Small Cell Lung Cancer” News Release. Florida Cancer Specialists & Research Institute, April 7, 2026
2. “PRESERVE-003 Stage 1 Evaluation of Gotistobart” by Dr. Adewale Fawole, et al., Nature Medicine

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