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Solid TumorPhase 1/2NCT05576961

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

A Phase 1/2 study testing RX-af01, Mixed bacteria and High dose RX-af01 in people with Solid Tumor and Immune Checkpoint Inhibitor, run by Sun Yat-sen University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RX-af01, Mixed bacteria and High dose RX-af01
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteChina
Study dates
15 Sep 2022to 31 Dec 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
  • Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of treatment, 5 months after the last dose of PD-1 inhibitor for women with childbearing potential, and 7 months after the last dose of PD-1 inhibitor for men
  • Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle stimulating [FSH] level > 40 mIU/mL to confirm menopause).

Who cannot join

  • 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
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  • 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:
  • Any active, known, or suspected autoimmune disease will be excluded, with the following exceptions: Type 1 diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment; conditions not expected to recur in the absence of an external trigger.
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before first dose of study treatment. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed.
  • Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection (with the DNA copy number >1000 copies/ml), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection.
  • Serious non-healing wound/ulcer/bone fracture.
  • Malabsorption syndrome.
  • Uncompensated/symptomatic hypothyroidism.
  • Moderate to severe hepatic impairment (Child-Pugh B or C).
  • Requirement for hemodialysis or peritoneal dialysis.
  • History of solid organ or allogenic stem cell transplant.
  • Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal, or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment. Furthermore, subjects with a history of additional risk factors for torsades de pointes (e.g., long QT syndrome) are also excluded.
  • Pregnant or lactating females
  • Inability to swallow tablets or unwillingness or inability to receive IV administration
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies.
  • Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 5 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

Trial locations and contacts

1 site in 1 country.

Miao-Zhen Qiu contact

+862087343351

qiumzh@sysucc.org.cn

Shuang-Zhen Chen contact

+862087343804

chenshuagnzh@sysucc.org.cn

China1 site, 1 recruiting

  • Miao-Zhen Qiu

    Guangzhou, Guangdong, 510060

    Miao-Zhen Qiu, +862087343351, qiumzh@sysucc.org.cn

    Miao-zhen Qiu, MD

    Recruiting

Other trials in China

About this study

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

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.

Read the detailed description

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
Being tested
RX-af01, Mixed bacteria, High dose RX-af01

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RX-af01Drug

    Also called 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.

  • Mixed bacteriaDrug

    Also called Toripalimab

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

  • High dose RX-af01Drug

    Also called Toripalimab

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

Study groups in NCT05576961
Study groupRoleWhat they receive
regular dose of RX-af01ExperimentalRX-af01 in combination with toripalimab
Receives: Drug: RX-af01
high dose of RX-af01Experimental5 times dose of RX-af01 in combination with toripalimab
Receives: Drug: High dose RX-af01
Mixed bacteriaExperimentalMixed bacteria in combination with toripalimab
Receives: Drug: Mixed bacteria

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate

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

    Measured: Up to 1 year

Secondary outcomes (5)

  1. Overall survival (OS)

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

    Measured: Up to 1 year

  2. Progression free survival (PFS)

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

    Measured: Up to 1 year

  3. Duration of response (DoR)

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

    Measured: Up to 1 year

  4. Change of tumor microenvironment

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

    Measured: Up to 1 year

  5. Comparison of the Shannon index (a measure of microbial diversity)

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

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2022
  2. Study start15 Sep 2022
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
RX-af01 and toripalimab
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05576961
Sponsor's protocol ID
RX-af01-SYSUCC
Status last verified
Jan 2024
First submitted
16 Sep 2022
Last updated
23 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RX-af01, Mixed bacteria and High dose RX-af01 in people with Solid Tumor and Immune Checkpoint Inhibitor, run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Miao-Zhen Qiu (+862087343351, qiumzh@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05576961.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.

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