Gotistobart: Promising, But Not Yet Practice-Changing
- Gotistobart showed an 18.5‑month vs. 10‑month median OS in previously treated squamous non-small cell lung cancer (NSCLC) (HR 0.56), an unusually strong signal in a setting where docetaxel has remained hard to beat.
- Dr. Raja Flores, chairman of the Department of Thoracic Surgery at Mount Sinai Health System, stresses that the data are early, small‑cohort, and from an exploratory stage.
- Effect softened with maturity and notable immune toxicity. The hazard ratio worsened from 0.46 to 0.56 with longer follow‑up, and immune‑related AEs were markedly higher with gotistobart (60% any‑grade; 33% grade ≥3), underscoring that a “manageable” safety profile does not mean minimal.
- Dr. Flores calls the result “very promising” but not practice‑changing, saying confirmation in the pivotal stage 2 trial is essential.
New survival data for gotistobart in squamous non-small cell lung cancer (NSCLC) impressed Dr. Raja Flores, chairman of the Department of Thoracic Surgery at Mount Sinai Health System, but did not fully convince him of the drug’s abilities. “These are impressive but early results,” Dr. Flores tells SurvivorNet Connect.
The patients in the study, who have metastatic squamous NSCLC that has already progressed on chemotherapy and immunotherapy, are difficult to treat and currently do not have many good options, Dr. Flores says.
A rise in median overall survival from 10 months to 18.5 months, “certainly gets your attention,” he adds.
The Latest Data
BioNTech and OncoC4 presented data from stage 1 of the phase III PRESERVE-003 trial at the 2026 World Conference on Lung Cancer (WCLC).
In 87 patients with previously treated squamous NSCLC:
- Median OS was 18.5 months with gotistobart versus 10.0 months with docetaxel (HR 0.56, p=0.0295).
- The data cutoff was July 17, 2026, with 25.4 months of median follow-up.
- Grade 3 or higher treatment-related adverse events (TRAEs) were similar in both arms: 44.4% with gotistobart, 48.8% with docetaxel.
Gotistobart is an investigational anti-CTLA-4 antibody. It is designed to deplete regulatory T cells (Tregs) inside the tumor while sparing CTLA-4 elsewhere.
The setting explains why the number stands out. Squamous NSCLC that has progressed on a PD-(L)1 inhibitor and platinum chemotherapy has been hard to improve for more than a decade. Docetaxel remains the default second-line option, with a median OS of about 8 to 10 months. Several newer regimens have tried to beat it in randomized trials and failed. A monotherapy reaching an 18.5-month median in that setting is not routine.
Dr. Flores Encourages Cautious Optimism
The sponsor described the result as nearly doubling survival, but Dr. Flores says he would not use that phrase.
“I think we have to be careful about saying the drug ‘nearly doubled survival,'” he says, adding that the cohort is fewer than 90 patients and this was the exploratory first stage of a trial whose confirmatory portion is still enrolling. “A difference this large is exciting, but we need to see if it holds up when you study more patients.”
He also flagged the part of the update the headline skips. The treatment effect got smaller as the data matured.
“In the updated analysis presented at WCLC, the HR actually moved from 0.46 in the earlier analysis to 0.56 with longer follow-up,” he explains. “The survival benefit remains substantial, but the apparent treatment effect became somewhat smaller as the data matured.”
At the earlier cutoff, published in Nature Medicine (14.5 months of follow-up), the gotistobart median had not been reached, and the hazard ratio was 0.46. About a year later, the median settled at 18.5 months, and the effect estimate softened.
“That is exactly why the ongoing pivotal stage 2 matters,” Dr. Flores says.
‘Another Way in’ to the Immune System
What interests Dr. Flores most is not this single result, but what the result says about using immunotherapy after immunotherapy.
These patients had already progressed on a PD-(L)1 inhibitor. “This suggests that just because a cancer stops responding to one form of immunotherapy doesn’t necessarily mean you’ve exhausted the immune system as a way of treating that cancer,” he explains. “Targeting CTLA-4 may be another way in.”
The biology fits that idea. Gotistobart releases CTLA-4 in the acidic space inside the cell, so the receptor returns to the surface instead of being destroyed. The aim is to deplete Tregs inside the tumor while limiting the body-wide blockade that causes ipilimumab-type toxicity. Squamous tumors tend to carry more mutations, more immune-cell infiltration, and frequent PTEN loss, which is linked to Treg infiltration. That makes squamous disease a plausible place for this mechanism to work.
Safety Considerations
The caution applies to safety too. The sponsor called the safety profile manageable and reported the similar grade ≥3 TRAE rates. The top-line number hides a clear difference in immune toxicity.
The peer-reviewed stage 1 paper, at the earlier cutoff, reported immune-related adverse events (irAEs) of any grade in 60% of gotistobart patients versus 10% with docetaxel. Grade ≥3 irAEs were 33% versus 5%. The main events were the usual CTLA-4 ones: colitis, hepatitis, and pneumonitis. About two-thirds of patients with an irAE needed corticosteroids.
A chemotherapy-free option is not toxicity-free. It trades cytopenias and febrile neutropenia for an immune profile that, in a real minority of patients, means steroids and a pause in treatment.
‘Not Practice-Changing — Yet’
The bottom line, Dr. Flores says, is that the results are “very promising, but I wouldn’t call it practice-changing yet.”
He is specific about what would change his mind. “If they reproduce an 18.5-month versus 10-month survival difference in the larger trial, then we’re talking about something that could really change how we treat these patients.”
That trial is already running. The pivotal stage 2 of PRESERVE-003 uses OS as its primary endpoint and is enrolling squamous NSCLC patients at more than 160 sites. Until it reports, gotistobart is a strong and interesting signal, and not yet a reason to change practice.
