Gotistobart Cuts Death Risk by 54% in Advanced NSCLC Trial

Findings from stage 1 of the PRESERVE-003 phase 3 clinical trial, published in Nature Medicine, show that the investigational immunotherapy gotistobart may improve survival outcomes for patients with metastatic non-small cell lung cancer (NSCLC), particularly those with squamous disease whose cancer has progressed after prior treatment. The study, conducted across multiple countries with participation from Florida Cancer Specialists & Research Institute, evaluated whether gotistobart could offer a more effective option with manageable side effects compared with Taxotere.

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 Taxotere (docetaxel). 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 Taxotere 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 Taxotere, 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 Taxotere. Responses to gotistobart also lasted longer, with a median duration of response of 11 months compared with 3.8 months for Taxotere. 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 Taxotere, although a trend toward improvement with gotistobart was observed.

In contrast, outcomes for patients with non-squamous NSCLC were numerically better in the Taxotere 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 Taxotere 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 Taxotere.

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 Taxotere. 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 Taxotere group.

Treatment-related side effects occurred in 84.4% of patients receiving gotistobart and 90.2% of those receiving Taxotere. 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 Taxotere, 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 Taxotere group. Severe immune-related side effects occurred in 33.3% of patients receiving gotistobart and 4.9% of those receiving Taxotere. 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 Taxotere. 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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