Gotistobart shows early survival advantage over docetaxel in pretreated squamous NSCLC

Gotistobart showed early survival results from the first stage of the phase 3 PRESERVE-003 trial as a chemotherapy-free treatment for certain patients with non-small cell lung cancer. In patients with metastatic squamous disease previously treated with a PD-L1 inhibitor or PD-1 inhibitor and platinum-based chemotherapy, overall survival had not been reached with gotistobart monotherapy compared with 9.95 months with docetaxel-based chemotherapy after a median follow-up of 14.5 months.

The trial enrolled patients aged 18 years or older with stage III-IV metastatic disease. In stage I, patients with metastatic squamous disease in the per-protocol analysis 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, while those on docetaxel received 75 mg/m2 every 3 weeks.

Overall survival was the primary endpoint. In patients with metastatic squamous disease, overall survival 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 (hazard ratio 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, at 20% versus 4.8% and 11.0 versus 3.8 months, respectively. Progression-free survival did not differ significantly between groups, with median progression-free survival of 2.4 months (95% CI, 2.1-4.5) for gotistobart and 2.6 months (95% CI, 2.1-3.9) for docetaxel (hazard ratio 0.69; 95% CI, 0.42-1.13).

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. 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.

Gotistobart is a pH-sensitive CTLA-4 antibody that depletes regulatory T cells in the acidic tumor microenvironment. In terms of safety, grade 3 or greater adverse events occurred in 42.2% and 48.3% of patients receiving gotistobart and docetaxel, respectively, while serious adverse events occurred in 42.2% versus 29.3%. There were two deaths in the gotistobart arm, though these were not considered treatment-related, and there were no unexpected toxicities in either group. The most commonly reported adverse events were gastrointestinal, hepatic lab abnormalities, and infusion-related reactions.

Data for patients with non-squamous NSCLC in stage I were not presented. The study was sponsored by OncoC4, and BioNTech SE conducted and collaborated on the study.