First-in-human study of CJRB-101, a live biotherapeutic product in combination with pembrolizumab in selected types of advanced or metastatic cancer.

8547 Background: CJRB-101 is a live biotherapeutic product containing a novel strain belonging in the species Leuconostoc mesenteroides . Preclinical data support the role of CJRB-101 in eliciting anti-tumor response via induction of macrophage and recruitment of GZMB + CD8 T cell, thereby eliciting synergy with pembrolizumab. Methods: This is a multi-national, open label, phase 1/2 study to evaluate the safety and preliminary efficacy of CJRB-101 with pembrolizumab in patients with non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and melanoma who are immune checkpoint inhibitor (ICI)-naïve or have progressed with ICIs. Patients were treated with pembrolizumab 200 mg every 3 weeks with dose level 1 (1 capsule QD) or 2 (2 capsules BID) of CJRB-101 until unacceptable toxicity or progression of disease. Exploratory endpoints included bulk RNA sequencing of baseline and post-treatment (prior to C2D1) FFPE samples. Results: As of Jan 17, 2025, a total of 32 patients were enrolled, including 13 ICI-naïve and 19 ICI-refractory patients. No dose limiting toxicity was observed in the lead in part (dose level 1, n=12) or in subsequent patients in level 2 (n=20). At a median follow-up of 59 days, the median number of treatment cycles was 3. Treatment-related adverse events accounted for 21.9% (n=7/32), mostly grade 1 or 2. Only 1 patient (3.2%) experienced grade > 3 TRAE which was anemia related to CJRB-101. Preliminary efficacy outcomes are shown in Table. Of the 20 patients deemed efficacy evaluable with at least 1 on-treatment scan (ICI naïve, n=10; ICI refractory, n=10), the ORR was 44% for ICI naïve, metastatic NSCLC (n=4/9), and DCR was 30% (n=3/10) for ICI-refractory NSCLC. Bulk-RNA sequencing of baseline samples (n=14) showed that patients who derived clinical benefit (CB, PR+SD, n=7) showed enrichment in T cell activation, and upregulation of innate and adaptive immune response compared to those with no-clinical benefit (NCB; PD, n=7). On treatment biopsied sample showed significant decrease in PD-1 + Tim-3 + CD4 (P=0.002) and CD8 (P=0.006) T cells in CB group compared to the NCB group. Conclusions: CJRB-101 plus pembrolizumab was well tolerated with manageable safety profile. Preliminary efficacy data show anti-tumor activity in metastatic NSCLC, and early biomarker data support the role of immune activation of CJRB-101. Exploratory analysis of PBMCs, multiplex IHC, PD biomarker, and fecal microbiota metagenomics analysis are ongoing. Clinical trial information: NCT05877430 . Preliminary efficacy outcomes. Confirmed ORR Treatment status Total ICI naive ICI refractory Tumor types (n) 10 10 20 NSCLC (n) 9 10 19 ORR (%) 44% 0% 21% DCR (%) 67% 30% 64% HNSCC (n) 1 0 1 DCR (%) 100% 0 100% Dose of CJRB-101 (n) 10 10 20 0 level (n=6) 4 2 6 ORR (%) 50% 0% 33% DCR (%) 50% 0% 33% 1 level (n=14) 6 8 14 ORR (%) 33% 0% 14% DCR (%) 83% 38% 57%