Anti-Infective Agents

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Vancomycin

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Immunoglobulins

5 times dose of RX-af01 in combination with toripalimab

Mixed bacteria in combination with toripalimab

Pretreatment： vancomycin: 125mg po, tid, D-6 to D-3 RX-af01: 2 capsules, bid, po, D-2 to D0 Treatment (Every 3 weeks) RX-af01: 1 capsule, bid, po, every day Toripalimab: 240mg, ivdrip, D1, every 3 weeks.

RX-af01

Pretreatment： vancomycin: 125mg po, tid, D-5 to D-3

Mixed bacteria

High dose RX-af01

Miao-Zhen Qiu

Shuang-Zhen Chen

Miao-zhen Qiu, MD

Rui-hua Xu, MD, PhD

This phase I trial evaluates the effects of RX-af01 in combination with toripalimab (PD-1 antibody), in treating patients with refractory advanced solid tumors, including melanoma, nasopharyngeal squamous carcinoma, esophageal squamous cell carcinoma, gastric adenocarcinoma, renal cell carcinoma, et al. RX-af01 is a kind of anti-tumor intestinal bacteria developed by our research group. Its main components are symbiotic bacteria from human intestine - Alisipes finegoldii (A. finegoldii.), which is a Gram negative anaerobic bacteria. Our previous research shows that A finegoldii. can significantly enhance the anti-tumor activity of PD-1 antibody in multiple mouse tumor models. Mechanism research shows that A finegoldii. can increase the infiltration of CD4 and CD8 positive immune cells in the tumor microenvironment, and enhances the anti-tumor activity of immune cells. The primary aim of this study is to explore the efficacy and safety of RX-af01 combined with PD-1 antibody in refractory advanced solid tumors.

This is a phase Ib study to evaluate the effects of RX-af01 in combination with toripalimab (PD-1 antibody), in treating patients with refractory advanced solid tumors, including melanoma, nasopharyngeal squamous carcinoma, esophageal squamous cell carcinoma, gastric adenocarcinoma, renal cell carcinoma, et al. This study will include 3 chorts. Cohort 1 uses the regular dose of RX-af01. Cohort 2 uses a high dose of RX-af01 which is 5 times of the regular dose of RX-af01. Cohort 3 uses a mixed bacteria including RX-af01, Bifidobacterium longum RX02 and Ligilactobacillus salivarius RX02.

Primary endpoint:

To determine the safety and efficacy of bacterial strain RX-af01 in combination with toripalimab in refractory advanced solid tumors.

Secondary endpoint:

1. Progression free survival (PFS)
2. Overall survival (OS)
3. Duration of response (DOR)
4. Tumor microenvironment
5. Changes in flora species/abundance

Safety and Efficacy of RX-af01 Combined With PD-1 Antibody

Safety and Efficacy of Bacterial Strain RX-af01 Combined With PD-1 Antibody in Patients With Refractory Advanced Solid Tumors

Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, including complete response (CR) and partial response (PR).

From the time of enrollment to the date of death or last followup.

From the time of enrollment to the date of disease progression or death or last followup.

The time from the first assessment of CR or PR to the first assessment of PD or death (caused by any reason)

Infiltration of immune cells, including CD8+T cell, Treg cell et al.

Using translational methods, will compute the Shannon index at baseline for a comparison of microbial diversity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Efficacy of RX-af01 Combined With PD-1 Antibody	NCT05576961	Solid Tumor Immune Checkpoi... Intestinal Flor...	RX-af01 Mixed bacteria High dose RX-af...	18 Years -	Sun Yat-sen University
Safety and Efficacy of RX-af01 Combined With PD-1 Antibody	NCT05576961	Solid Tumor Immune Checkpoi... Intestinal Flor...	RX-af01 Mixed bacteria High dose RX-af...	18 Years -	Sun Yat-sen University

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