Dr Socinski on Data From Stage 1 of the PRESERVE-003 Trial in Squamous NSCLC

“We are excited about this. However, we realize that this is a small data set and sometimes with small data sets prognostic factors may not be entirely clear. The question that we’re trying to address in stage 2 of this trial is whether this pretty impressive survival benefit seen in this stage 1 analysis is going to carry through to the larger population.”

Mark A. Socinski, MD, a medical oncologist at Advent Health, discussed data from stage 1 of the phase 3 PRESERVE-003 trial (NCT05671510), which showed a 54% reduction in the risk of death with gotistobart vs docetaxel in squamous non–small cell lung cancer (NSCLC) following PD-(L)1 and platinum-based therapy.

Gotistobart (BNT316/ONC-392) is an investigational pH-sensitive anti–CTLA-4 monoclonal antibody that was compared with docetaxel in patients with pretreated, metastatic squamous NSCLC in PRESERVE-003. Among 87 patients with squamous histology, 45 were treated with gotistobart at 6 mg/kg following two loading doses of 10 mg/kg every 3 weeks and 42 with docetaxel, Socinski explained. The median overall survival (OS) had not been evaluable (NE) with gotistobart (95% CI, 9.33 months-NE) at a median follow-up of 14.5 months (IQR, 13.0-16.4) compared with 9.95 months (95% CI, 6.18-11.93) at a median follow-up of 15.2 months (IQR, 11.5-16.0) with docetaxel (HR, 0.46; 95% CI, 0.25-0.84; nominal P = .0102). The 12-month OS rates were 63.1% (95% CI, 46.9%-75.5%) and 30.3% (95% CI, 16.2%-45.6%), respectively. The survival data, though preliminary given the small data set, are highly encouraging, Socinski remarked.

Additional data showed that the confirmed objective response rate was 20.0% with gotistobart vs 4.8% with docetaxel, with a median duration of response of 11.0 months (95% CI, 3.5-NE) and 3.8 months (95% CI, 3.6-NE), respectively. The 12-month progression-free survival rate was 25.2% with gotistobart vs 0% with docetaxel (HR, 0.69; 95% CI, 0.42-1.13).

The safety profile was consistent with the established profiles of both agents. Grade 3 or greater treatment-related adverse effects occurred in 42.2% of patients in the gotistobart arm vs 48.8% in the docetaxel arm, with immune-mediated events including colitis (8.9%) and hepatic transaminase elevations representing the most notable gotistobart-associated toxicities, while myelosuppression predominated with docetaxel. Investigators noted no unexpected toxicities in either arm.

Enrollment is nearing completion for the pivotal stage 2 portion of PRESERVE-003, which is enrolling patients with squamous NSCLC to confirm these findings in a larger cohort. If the survival benefit holds up in the stage 2 portion, the agent has the potential to become a new standard of care for individuals who progress on chemoimmunotherapy, Socinski concluded.