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

NCT05576961 | Unknown Phase 1

• 1 other identifier: RX-af01-SYSUCC
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor; Immune Checkpoint Inhibitor; Intestinal Flora

Outcome Measures

Primary Outcomes (1)

• Objective response rate

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

  Up to 1 year

Secondary Outcomes (5)

• Overall survival (OS)

  Up to 1 year

• Progression free survival (PFS)

  Up to 1 year

• Duration of response (DoR)

  Up to 1 year

• Change of tumor microenvironment

  Up to 1 year

• Comparison of the Shannon index (a measure of microbial diversity)

  Up to 1 year

Study Arms (3)

regular dose of RX-af01

EXPERIMENTAL

RX-af01 in combination with toripalimab

Drug: RX-af01

high dose of RX-af01

EXPERIMENTAL

5 times dose of RX-af01 in combination with toripalimab

Drug: High dose RX-af01

Mixed bacteria

EXPERIMENTAL

Mixed bacteria in combination with toripalimab

Drug: Mixed bacteria

Interventions

RX-af01 DRUG

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.

Also known as: Toripalimab

regular dose of RX-af01

Mixed bacteria DRUG

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

Also known as: Toripalimab

Mixed bacteria

High dose RX-af01 DRUG

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

Also known as: Toripalimab

high dose of RX-af01

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) solid tumors, including melanoma, nasopharyngeal squamous carcinoma, esophageal squamous cell carcinoma, gastric adenocarcinoma, renal cell carcinoma, et al.
• Fail to or could not tolerate standard treatment.
• Receive at least 2 cycles of PD-1/PD-L1/CTLA4 inhibitors and the response is complete response (CR) or partial response (PR) or stable disease (SD).
• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Recovery to baseline or =\< grade 1 CTCAE v5 from toxicities related to any prior treatments unless adverse events (AE\[s\]) are clinically nonsignificant and/or stable on supportive therapy
• ECOG performance status score: 0-1
• Males and females, ages \>= 18
• Absolute neutrophil count (ANC) \>= 1500/uL without granulocyte colony-stimulating factor support (within 14 days before first dose of study treatment)
• Platelets \>= 90,000/uL without transfusion (within 14 days before first dose of study treatment)
• Hemoglobin \>= 8 g/dL (\>= 80 g/L) (within 14 days before first dose of study treatment)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) =\< 3 x upper limit of normal (ULN). ALP =\< 5 x ULN with documented bone metastases (within 14 days before first dose of study treatment) Total bilirubin =\< 1.5 x ULN (for subjects with Gilbert's disease =\< 3 x ULN) (within 14 days before first dose of study treatment)
• Serum albumin \>= 3.0 g/dl (within 14 days before first dose of study treatment)
• Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN (within 14 days before first dose of study treatment)
• Serum creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 40mL/min (\>= 0.675 mL/sec) using the Cockcroft-Gault equation (within 14 days before first dose of study treatment)
• Urine protein/creatinine ratio (UPCR) =\< 1 mg/mg (=\< 113.2 mg/mmol), or 24-hour (h) urine protein =\< 1 g (within 14 days before first dose of study treatment)

You may not qualify if:

• Current use, or intent to use, probiotics, yogurt, or bacterial fortified foods during the period of treatment
• Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
• Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
• Administration of a live, attenuated vaccine within 30 days before first dose of study treatment
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of study treatment.
• Subjects with a diagnosis of incidental, subsegmental pulmonary embolism (PE) or deep vein thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation for at least 1 week before first dose of study treatment.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study treatment
• Other clinically significant disorders that would preclude safe study participation:

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Miao-Zhen Qiu

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Interventions

toripalimab

Central Study Contacts

Miao-Zhen Qiu

CONTACT

+862087343351; qiumzh@sysucc.org.cn

Shuang-Zhen Chen

CONTACT

+862087343804; chenshuagnzh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: RX-af01 and toripalimab

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: October 13, 2022
• Study Start: September 15, 2022
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 23, 2024

Record last verified: 2024-01

Locations

CN (1)