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

Exclusion Criteria

• •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
• •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:
• •1. 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.
• •2. 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.
• •3. 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.
• •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.