Gotistobart Improves Survival vs Docetaxel in Metastatic NSCLC Trial

Treatment with gotistobart meaningfully improved overall survival (OS) compared with docetaxel among patients with metastatic squamous non–small cell lung cancer (NSCLC), according to findings from the phase 3 PRESERVE-003 trial (NCT05671510) published in Nature Medicine.¹

After a median follow-up of 14.5 months (range, 0.1-18.8), the median OS was not reached (NR; 95% CI, 9.3 months to not evaluable [NE]) with gotistobart vs 10.0 months (95% CI, 6.2-11.9) with docetaxel (HR, 0.46; 95% CI, 0.25-0.84; P = .0102). Data showed 12-month OS rates of 63.1% (95% CI, 46.9%-75.5%) vs 30.3% (95% CI, 16.2%-45.6%) in each respective arm.

Investigators reported a median progression-free survival (PFS) of 2.4 months (95% CI, 2.1-4.5) with gotistobart and 2.6 months (95% CI, 2.1-3.9) with docetaxel; a trend towards favorable PFS was noted in the experimental arm (HR, 0.69; 95% CI, 0.42-1.13). Additionally, the confirmed objective response rate (ORR) was 20.0% (95% CI, 9.6%-34.6%) and 4.8% (95% CI, 0.6%-16.2%) in each arm, with respective median duration of responses (DORs) of 11.0 months (95% CI, 3.5-NE) and 3.8 months (95% CI, 3.6-NE).

OS and PFS outcomes were numerically higher with docetaxel vs gotistobart among patients with nonsquamous NSCLC who received the experimental agent at 6 mg/kg every 3 weeks with 2 loading doses of 10 mg/kg, supporting the data monitoring committee’s recommendation to halt clinical development for the nonsquamous population. Additionally, poor outcomes in patients with squamous or nonsquamous disease who received gotistobart at 3 mg/kg every 3 weeks supported the data monitoring committee’s recommendation to terminate the low-dose cohort.

“This randomized study demonstrates a clinically meaningful improvement in OS with a novel immunotherapy monotherapy compared to docetaxel in patients with [squamous] NSCLC who experience disease progression on or after anti–PD-(L)1 treatment, given either in combination with or after [platinum-based chemotherapy],” lead study author Byoung Chul Cho, MD, PhD, from the Division of Medical Oncology at Yonsei Cancer Center in Seoul, South Korea, wrote with coauthors in the publication.¹ “[W]ith a 54% reduction in the risk of death over docetaxel and manageable toxicity, the results from the nonpivotal stage 1 of this phase 3 randomized study suggest that gotistobart may offer a chemotherapy-free treatment option to transform the treatment paradigm of [squamous] NSCLC with better outcomes for patients.”

In stage 1A of the 2-stage, open-label PRESERVE-003 trial, 120 patients were randomly assigned 1:1:1 to receive to gotistobart at 3 mg/mg every 3 weeks, gotistobart at 6 mg/kg with 2 loading doses of 10 mg/kg every 3 weeks, or docetaxel at 75 mg/m² every 3 weeks. As part of the ongoing stage 2 portion of the trial, patients with squamous disease were randomly assigned 1:1 to receive gotistobart at 6 mg/kg or docetaxel.

The trial’s primary end point was OS. Secondary end points included investigator-evaluated PFS and ORR per RECIST v1.1 criteria, as well as safety.

Patients 18 years and older with histologically or cytologically confirmed metastatic squamous NSCLC, radiographic progression after treatment on the most recent line of therapy, and at least 1 measurable lesion per RECIST v1.1 guidelines were eligible for enrollment on the trial.² Additional requirements for study entry included having an ECOG performance status of 0 or 1, adequate organ function, and a life expectancy of at least 3 months.

Among 45 patients who received gotistobart and 42 who received docetaxel, respectively, the median age was 64.0 years (range, 39-86) and 68.5 years (range, 43-84), and most patients from each arm were male (80.0% vs 90.5%) and Asian (71.1% vs 71.4%). Additionally, most patients from each arm had an ECOG performance status of 1 (80.0% vs 83.3%), former smoking status (75.6% vs 64.3%), and 1 prior line of treatment in the advanced or metastatic setting (66.7% vs 71.4%).

Adverse effects (AEs) of any grade occurred in 84.4% of patients in the gotistobart arm and 90.2% of those in the docetaxel arm, with 42.2% and 48.8% experiencing grade 3 or higher AEs, respectively. The most common any-grade AEs in the gotistobart arm included increased alanine aminotransferase (28.9% vs 9.8%), diarrhea (28.9% vs 9.8%), and increased aspartate aminotransferase (26.7% vs 4.9%).

Serious AEs related to study treatment were noted in 42.2% of the gotistobart arm and 29.3% of the docetaxel arm. The most common serious AEs included colitis (11.1%), immune-mediated lung disease (6.7%), and pneumonia (4.4%) in the gotistobart arm and pneumonia (9.8%) and febrile neutropenia (7.3%) in the docetaxel arm.

References

1. Cho BC, Balaraman R, Chen H-J, et al. Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial. Nat Med. Published online March 27, 2026. doi:10.1038/s41591-026-04323-8
2. ONC-392 versus docetaxel in metastatic NSCLC that progressed on PD-1/​PD-L1 inhibitors (PRESERVE-003). ClinicalTrials.gov. Updated February 25, 2026. Accessed April 8, 2026. https://tinyurl.com/5487pt8v