Gotistobart Shows Survival Benefit in Pretreated Lung Cancer

Gotistobart (ONC-392) improved responses and showed a survival benefit compared with docetaxel in patients with previously treated squamous non–small cell lung cancer (NSCLC), according to stage 1 data from the phase 3 PRESERVE-003 trial presented at the 2026 European Lung Cancer Congress.

The objective response rate was 20% with gotistobart versus 4.8% with docetaxel, with longer-lasting responses (11 months versus 3.8 months). While progression-free survival was similar, more patients receiving gotistobart remained progression-free at 12 months (25.2% versus 0%), and overall survival was not yet reached compared with 9.95 months for docetaxel.

Dr. Josh Sabari, editor-in-chief of CURE and a thoracic medical oncologist at NYU Langone Health Perlmutter Cancer Center, said a 20% response rate is meaningful in this setting, where standard options often lead to limited and short-lived responses. He noted that overall survival is the most important measure and highlighted that some patients experienced longer-term disease control with gotistobart.

The treatment may offer a chemotherapy-free option for patients whose cancer has progressed after immunotherapy and chemotherapy. Side effects included immune-related events such as colitis and liver enzyme changes, which are generally manageable, and low rates of pneumonitis.

Stage 2 of the trial is ongoing to better understand safety, durability of response and long-term outcomes.

CURE: The PRESERVE-003 trial showed a higher response rate with gotistobart compared with docetaxel in previously treated squamous NSCLC. How meaningful is a 20% response rate in this treatment-resistant setting?

Sabari: Squamous cell carcinomas are less common now in the lung cancer space. These are most seen in people who’ve smoked. First-line therapies like KEYNOTE-407, carboplatin, paclitaxel and Keytruda (pembrolizumab) have decent response rates. But unfortunately, the durability is quite poor in the second-line setting. We compare a lot of our new agents to docetaxel. Response rates to docetaxel are 5% to 10% on average, and the durability there is poor as well, in the range of one to two months. So gotistobart is a novel CTLA-4 inhibitor, and having a response rate in that 20% range in this heavily pretreated patient population — meaning they have had prior PD-1 or PD-L1 inhibitor therapy and prior chemotherapy — is quite impressive.

Although progression-free survival appeared similar between arms, overall survival favored gotistobart. How should clinicians interpret this disconnect when thinking about treatment benefit?

Overall survival is key for us when we’re evaluating novel therapies. Progression-free survival is also important because it allows us to understand how long patients remain without disease growth, and it allows them to have better quality of life. I think both are important in our patient population. One interesting thing about the study is if you look at 12 months, 22.5% of patients were progression-free with gotistobart versus 0% progression-free at 12 months with docetaxel alone. So clearly, there is some benefit for patients with this disease.

Gotistobart is being positioned as a chemotherapy-free option. For patients who have already received prior immunotherapy and chemotherapy, how significant is the potential to move away from traditional cytotoxic agents?

The one therapy that patients do not want to get when they come in to see me in my office is chemotherapy, right? A lot of times we’re convincing patients of the benefits of chemotherapy, and I think there is a true role in the frontline setting. In the second-line setting, particularly in squamous cell histology, therapies like docetaxel or gemcitabine have largely been ineffective. I think it’s great that we may have another option for our patients, particularly one that is chemotherapy-free, with a novel CTLA-4 inhibitor.

The mechanism of gotistobart involves selective depletion of regulatory T cells in the tumor microenvironment. How might this approach differ clinically from earlier CTLA-4–targeting therapies?

It’s interesting. A lot of our CTLA-4 inhibitors as single agents have failed in the non-small cell lung cancer space. Most of our successes have been in combination with PD-1 or PD-L1 inhibitors. Think about Yervoy (ipilimumab) and Opdivo (nivolumab). Think about therapies like Imjudo (tremelimumab), for example, and Imfinzi (durvalumab). But here, with gotistobart, there’s a truly novel mechanism of action, and I think it might be complementary to the immune activation that you see with prior PD-1 or PD-L1 checkpoint inhibition.

The safety profile showed immune-related toxicities, including colitis and liver enzyme elevations. How manageable were these side effects in practice, and what should care teams be prepared for?

We never like to see side effects in patients, because it affects quality of life. But when we look at side effects, we’re trying to understand whether it’s in line with the biology or mechanism of the disease. To see immune-related side effects with gotistobart is promising, because we are activating the immune system to better recognize and attack cancer. So immune-mediated side effects are quite common in our clinical practice setting, and we have a lot of experience with immunosuppression, for example, and dose holds in this patient population. Anyone in practice now is experiencing these side effects — thyroid issues, for example, colitis issues, for example. I think the one immune-related side effects that worries us most is pneumonitis, and that was relatively low in this study.

With stage 2 of PRESERVE-003 ongoing in squamous NSCLC, what key questions still need to be answered before gotistobart could become part of standard treatment?

We’re really looking forward to seeing the data for the second phase of this trial of gotistobart. I think one important thing for us is to understand the ongoing safety in a larger patient population, but also to understand the durability of response — how long patients are on therapy, and what the true overall survival is. Questions that I’m not sure we’ll see in this trial are CNS penetration. One thing I’d like to understand is rates of progression in the brain. If this therapy can improve progression rates in the brain, that is a very important aspect of these therapies. A lot of our patients, unfortunately, do have CNS progression, leading to a lot of morbidity and mortality as well.

Transcript has been edited for clarity and conciseness.

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