Abstract CT065: Results of a phase 1 multicenter study on Oncobax®-AK with immunotherapy in renal cell carcinoma (NCT 05865730)

Abstract Background: Patients with advanced solid tumors who respond to immunotherapy are more likely to have Akkermansia spp (Akk) in their stools. Its absence (in ∼45% of patients) is linked to poorer outcomes, independently of other clinical prognostic factors. We present safety and efficacy results from a Phase I study of Oncobax®-AK live biotherapeutics combined with nivolumab plus ipilimumab in intermediate- and poor-risk IMDC renal cell carcinoma (RCC) patients who tested negative for stool Akk. Methods: Intermediate and poor risk IMDC RCC were screened for the presence of Akk using a qPCR stool test. This test was designed to detect specific Akk (SGB9226 and 9228). Only patients who tested negative for stool Akk received 1X oral capsules of Oncobax-AK (a specific strain of SGB9228, p2261) alone for 1 week, followed by a combination with nivolumab plus ipilimumab continuously until progression. The primary endpoints were safety, pharmacodynamics of Oncobax®-AK and overall response rate (ORR) according to RECIST 1.1. Blood and stools were collected at different time points for multi-omics pharmacodynamic analyses. Results: Of the 29 patients assessed for eligibility, 11 (38%) did not harbor gut Akk spp. Among them, 2 patients refused to continue in the trial. We finally enrolled 9 patients. The median age was 57 years (n=9: 1 F and 8 M). Of these 9 pts, 8 had an intermediate and 1 had a poor IMDC risk score. No Oncobax-AK-related serious adverse events were observed. Only one patient had a serious immunotherapy-related adverse event that led to treatment withdrawal. After a median follow up of 14.9 months, all patients are still alive and 4 pts had a partial response (PR) for > 6 months (including 2 pts with ongoing PR for over 15 months, continuing the intervention). One pt had stable disease (SD), 3 had progressive disease (PD), and 1 was not evaluable (NE). Among the evaluable patients, the ORR was 50%. Multi-omics analyses reviled that Oncobax®-AK remains detectable over time and induced changes in the microbiome, leaky gut markers, immune and metabolite profiles. These changes suggest potential pharmacodynamic biomarkers, as they reflect the biological effects of Oncobax®-AK and its role in modulating gut integrity, immune responses, and metabolic pathways, which may be associated with clinical outcomes. Conclusion: This is the first trial targeting patients lacking Akkermansia spp. in their stools. Oncobax®-AK combined with immunotherapy in intermediate- and poor-risk IMDC renal cell carcinoma appears safe and may modulate gut microbiota, inflammation, metabolites, and immune profile, potentially mimicking a responder's profile and leading to clinical and radiological benefits in some patients. Based on these promising results, enrollment is ongoing and has now been expanded to include non-small cell lung cancer patients with a dose escalation up to 6X. Citation Format: Lisa Derosa, Philippe Barthélémy, Brigitte Laguerre, François Giringhelli, everImmune, Fabrice Barlesi, Bernard Escudier, Laurence Zitvogel, Larence Albiges. Results of a phase 1 multicenter study on Oncobax®-AK with immunotherapy in renal cell carcinoma (NCT 05865730) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT065.