Norton Cancer Institute is enrolling metastatic lung cancer patients in a Phase 3 clinical trial to test a promising new anti-CLTA-4 antibody, gotistobart (ONC-392).

The study will test whether gotistobart is more effective than the chemotherapy agent docetaxel in prolonging life in patients with metastatic, non-small cell lung cancer whose disease progressed on anti-PD-1/PD-L1 antibody therapy.

“We’re excited to be offering this clinical trial. Immunotherapy agents show great potential for advancing the treatment we’re able to offer our patients,” said John T. Hamm, M.D., medical oncologist with Norton Cancer Institute and a principal investigator in the study. Dr. Hamm is director of Norton Cancer Institute’s research program and chairman of the Norton Hospital Cancer Committee.

Approximately 600 patients will be enrolled worldwide. Norton Cancer Institute is among the first cancer centers to begin enrolling patients in the study, NCT05671510 at ClinicalTrials.gov.

During the first stages of the Phase 3 trial, two gotistobart dosing regimens will be tested. One dosage will be selected for the second stage. Stage 2 will assess the safety and efficacy of gotistobart at the selected dosing regimen versus docetaxel.

In the yearlong trial, patients will be randomized and treated with either the study drug, gotistobart, or docetaxel, by IV infusion once every 21 days, for up to 17 cycles.

The primary endpoint of the study will be overall survival. Secondary endpoints are overall response rate, progression-free survival and adverse event profile.

About gotistobart

Gotistobart is a highly selective, humanized monoclonal IgG1-kappa isotype antibody against cytotoxic T-lymphocyte-associated protein 4, a cell surface protein receptor that works to ensure proper function of regulatory T cells.

Anti-CTLA-4 monoclonal antibodies have demonstrated strong immunotherapeutic effects in a variety of preclinical models and are used clinically both as monotherapy and as part of combination therapy with nivolumab (anti-PD-1).

In combination with anti-PD-1 therapy, they have resulted in significantly improved response rates and patient survival in multiple types of cancer and induced long-lasting immunity in cancer patients.

However, CTLA-4 monotherapy has resulted in more immunotherapy-related adverse effects than anti-PD-1/PD-L1 therapy, limiting tolerability.

The checkpoint inhibitor gotistobart was identified through in vivo screening in humanized CTLA-4 mouse model for high anti-tumor efficacy and low autoimmune toxicity.

The joint OncoC4-BioNTech-sponsored study, PRESERVE-003, follows an earlier, open-label Phase 1A/1B trial that showed promising results looking at the safety and efficacy of gotistobart as a single agent and in combination with pembrolizumab in advanced solid tumors and NSCLC. Norton Cancer Institute enrolled 24 patients in that trial.

About 80% to 85% of lung cancers are non-small cell lung cancer. This includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. These subtypes are grouped together as NSCLC even though they start in different types of lung cells, because their treatment and prognoses are often similar.

With NSCLC, as with most cancers, the survival rate drops significantly once the cancer has spread.

Five-year survival for localized NSCLC is 65%. That drops to 37% for regional NSCLC, which has spread from the lung to the lymph nodes, and 9% for metastatic NSCLC.