Early survival results from the first stage of a phase 3 study suggest that gotistobart, a new antibody associated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), has potential as a chemotherapy-free treatment for certain patients with non-small cell lung cancer (NSCLC).

Study author Kai He, MD, presented results from the two-stage PRESERVE-003 trial with patients aged 18 years or older with stage III-IV metastatic disease at the annual European Lung Cancer Congress (ELCC) 2026 in Copenhagen. The results were published simultaneously in Nature Medicine.

Gotistobart is a pH-sensitive CTLA-4 antibody that depletes regulatory T cells in the acidic tumor microenvironment, helping the immune system attack cancer while limiting effects on the rest of the body, according to He, who was a medical oncologist at The Ohio State University’s James Cancer Hospital in Columbus, Ohio, at the time of the trial.

All patients had previously received a PD-L1 inhibitor or PD-1 inhibitor and platinum-based chemotherapy, with prior dual immunotherapy treatment allowed. About 7% of trial participants had previously received a different anti-CTLA-4 treatment.

He reported on patients with metastatic squamous disease in stage I of the trial (n = 87 in per-protocol analysis). These patients were randomly assigned to gotistobart (n = 45) or docetaxel (n = 42). Those randomly assigned to gotistobart received 6 mg/kg every 3 weeks with two loading doses of 10 mg/kg every 3 weeks. Those on docetaxel received 75 mg/m² every 3 weeks.

In 14.5 months of median follow-up, overall survival (OS) — the primary endpoint — had not been reached with gotistobart monotherapy (95% CI, 9.3 to not estimable) compared with 9.95 months (95% CI, 6.8-11.93) with docetaxel-based chemotherapy in patients with metastatic squamous disease (hazard ratio [HR], 0.46; 95% CI, 0.25-0.84; P = .01 [nominal]).

Secondary endpoints also favored gotistobart. Patients treated with gotistobart had a higher objective response rate and a longer median duration of response than those receiving docetaxel (20% vs 4.8% and 11.0 vs 3.8 months, respectively).

Progression-free survival (PFS) did not differ significantly between groups, with median PFS of 2.4 months (95% CI, 2.1-4.5) for gotistobart and 2.6 months (95% CI, 2.1-3.9) for docetaxel (HR, 0.69; 95% CI, 0.42-1.13).

The groups were roughly comparable in terms of age and mostly male. Overall, 71% of patients were Asian, and roughly 25% were White. Liver and brain metastases were more common at baseline among patients receiving gotistobart than among those receiving docetaxel.

In terms of safety, grade 3 or greater adverse events occurred in 42.2% and 48.3% of patients receiving gotistobart and docetaxel, respectively. Serious adverse events occurred in 42.2% vs 29.3% of patients on gotistobart vs docetaxel. There were two deaths in the gotistobart arm, though these were not considered to be treatment-related. There were no unexpected toxicities in either group.

“The observed overall safety profile of gotistobart aligns with its previously established safety profile,” said He. The most commonly reported adverse events were gastrointestinal, hepatic lab abnormalities, and infusion-related reactions.

Invited discussant Jhanelle E. Gray, MD, compared the results with several trials of second-line squamous NSCLC, including TROPION-Lung01 (Ahn [2025]), EVOKE-01 (Paz-Ares [2024]), and S2302 Pragmatica-Lung (Dragnev [2025]). She noted that, in this context of these other studies, “you can see the overall response rate is pretty impressive [with gotistobart]. It appears that this is significant enough and impressive enough to drive a median overall survival that has yet to be reached.”

“For gotistobart (anti-CTLA-4), in patients with squamous NSCLC, where over 80% of patients were previously treated with chemoimmunotherapy, the early OS data are intriguing. We obviously await stage I and stage II results of the PRESERVE-003 study,” said Gray, who is chair of thoracic oncology at H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida. The study author did not present data for patients with non-squamous NSCLC in stage I.

“We also need to follow this data not just for efficacy but also for toxicity, patient-reported outcomes, future combination strategies, and how they compare to other emerging therapeutic approaches,” she said.

He reported having financial relationships with several pharmaceutical companies, including OncoC4, which sponsored the study, and BioNTech SE, which conducted and collaborated on the study. Gray reported having significant relationships, including research support and consulting/advisory roles, with several pharmaceutical companies.