KEY TAKEAWAYS
- The phase 2 trial aimed to analyze whether OBP-301 + pembrolizumab improves immunotherapy in advanced gastric cancer.
- OBP-301 with pembrolizumab showed encouraging activity in GEA.
For a new phase 2 multicenter study, researchers aimed to investigate OBP-301 combined with pembrolizumab and determine if it enhances immunotherapy for advanced gastric cancer.
Patients who were eligible for the study had advanced gastrointestinal cancers and had seen progression after at least two prior treatments. They received OBP-301 via direct tumor injection every 2 weeks for a total of 4 injections, alongside pembrolizumab administered intravenously every 3 weeks.
The study aimed to determine the objective response rate (ORR). To proceed to the second stage of the study, at least 3 responses among 18 patients were required in the initial stage, adhering to a Simon two-stage design.
The study was closed after completing the first stage of this design, investigating OBP-301 combined with pembrolizumab in an immunotherapy-resistant population with gastrointestinal cancers. Tissue samples were collected for single-cell RNA sequencing to assess changes in the tumor’s immune environment before and after OBP-301 injections.
Between May 2019 and October 2022, the study involved 16 patients, with a median age of 65 (ranging from 43 to 81), predominantly male (n=13). The direct tumor injection of OBP-301 was generally well tolerated, with a median of 3 injections per patient (ranging from 1 to 5).
Some observed toxicities linked to OBP-301 included moderate to severe fatigue/weakness in 37.5% of cases, fever in 12.5%, and elevated liver function tests in 12.5%. Remarkably, 2 patients (13%) displayed a partial response, and 1 patient achieved a complete response, meeting the criteria set by the Simon two-stage threshold.
These responses were sustained, with two patients showing no signs of disease and the third patient receiving 16 months of therapy before experiencing progression.
Notably, one patient with brain metastases demonstrated regression of metastatic disease after progression on immunotherapy alone. All patients exhibited proficient mismatch repair. The complete response was linked with a delayed increase in CD8 cytotoxic T cells, as evidenced by single-cell RNA sequencing expression.
OBP-301 combined with pembrolizumab demonstrated promising results in treating GEA, even in cases resistant to immunotherapy. Long-term responses are observed, and a formal phase II study for immunotherapy-refractory GEA patients is ongoing.
Source: https://jitc.bmj.com/content/11/Suppl_1/A666
Clinical Trial: https://clinicaltrials.gov/study/NCT03921021
Sarkar S, Khan S, Eads JR, et al586 Phase II study of Telomelysin (OBP-301) in combination with pembrolizumab in gastroesophageal (GEA) adenocarcinomaJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0586.
