Safety, Tolerability, and Preliminary Efficacy of CJRB-101 With Pembrolizumab in Subjects With Selected Types of Advanced or Metastatic Cancer

Study Overview
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Brief Summary
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Study CJB-101-01 will be conducted at multiple centers in the USA and Republic of Korea as an open-label safety and preliminary efficacy study of CJRB-101 in combination with pembrolizumab in subjects with selected types of advanced or metastatic cancer. The proposed study intends to address the unmet medical needs of low response rate and refractoriness to immune checkpoint inhibitors typically observed in this subject population by performing assessments of response, dose limiting toxicities, pharmacodynamic, and the effect on microbiome biomarkers at different dose levels of CJRB-101 combined with pembrolizumab.

Official Title
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Phase 1/2 Open Label, Safety and Preliminary Efficacy Study of a Live Biotherapeutic Product (CJRB-101) in Combination With Pembrolizumab in Subjects With Selected Types of Advanced or Metastatic Cancer

Conditions
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NSCLC, HNSCC, Melanoma, Metastatic Cancer, Advanced Solid Tumor, Advanced Cancer

Intervention / Treatment
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* Drug: CJRB-101
* Drug: Pembrolizumab injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide informed consent ≥18 years of age at the time of signing the informed consent form Pathologically documented histological or cytological evidence of NSCLC, HNSCC, or melanoma. Has at least 1 measurable target lesion per RECIST v1.1 that has not been resected/biopsied/or irradiated before enrollment in the study Diagnosis of locally advanced unresectable or metastatic NSCLC, HNSCC, or melanoma in subjects who are ICI treatment-naive or relapsed/refractory, including PD-1/PD-L1 inhibitors ICI treatment-naive subjects must meet the following criteria: NSCLC: Subjects with metastatic or with unresectable, recurrent NSCLC whose tumors must have no EGFR or ALK genomic aberrations and express PD-L1 [TPS≥50%] HNSCC: Subjects with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [CPS ≥20] Melanoma: Irrespective of PD-L1 result and BRAF V600 mutation Subjects has not received prior systemic treatment for their metastatic tumor. Subjects who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months before the development of metastatic disease. ICI treatment-refractory subjects as defined by the following criteria: Has received at least 2 cycles of anti-PD-(L)1 therapy either as monotherapy or in combination Has demonstrated disease progression after ICI treatment by RECIST v1.1 Has received less than three lines of systemic therapy for metastatic tumor ECOG performance status of 0 or 1 Be willing to provide archival tissue or fresh biopsy Have adequate organ function All Grade 3 or greater AEs resolved earlier to Grade 2 or less Exclusion Criteria: Cancer type and genomic tumor aberrations: NSCLC subjects with EGFR or ALK genomic tumor aberrations HNSCC subjects with nasopharyngeal cancer For ICI refractory/relapsed subjects: Immune related AEs ≥Grade 3 that led to discontinuation of prior immune-modulatory agents including PD-1/PD-L1 inhibitors With uncontrolled or untreated brain metastasis or leptomeningeal disease Active autoimmune disease that has required systemic treatment in the past 2 years Received a fecal transplant Concurrent participation in another interventional clinical study or use of another investigational agent within 30 days of study consent Contraindication to IV contrast that cannot be managed with pre-medication Female subjects who are pregnant or breastfeeding Male subjects who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy Has a known inability for oral intake of capsules Has received a live vaccine within 4 weeks of start of the study treatment Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy Has received whole blood transfusion, blood component transfusion, or colony stimulating factors within 1 week prior to the 1st dose of study treatment In the judgment of the investigator, subjects unlikely to comply with study procedures, restrictions and requirements Has active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids Have allergy to clindamycin, erythromycin, and ampicillin Has signs and symptoms of colitis at screening Infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before study treatment (Note: Antiviral therapy is permitted for subjects with chronic HBV or HCV infection) Untreated chronic hepatitis B or chronic HBV carriers with HBV DNA>500 IU/mL (or >2500 copies/mL) at screening (Note: Inactive hepatitis B surface antigen (HbsAg) carriers, treated and stable hepatitis B (HBV DNA < 500 IU/mL or < 2500 copies/mL) can be enrolled. Subjects with detectable HbsAg or detectable HBV DNA should be managed per treatment guidelines. Subjects receiving antivirals at screening should have been treated for > 2 weeks before study treatment.) With active hepatitis C (Note: Subjects with a negative HCV antibody test at screening or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening are eligible. The HCV RNA test will be performed only for subjects testing positive for HCV antibody. Subjects receiving antivirals at screening should have been treated for > 2 weeks before study treatment.) Known history of HIV infection History of active inflammatory bowel disease with diarrhea believed to be caused by active inflammatory bowel disease in the past 12 months Major surgery for any reason, except diagnostic biopsy, within 4 weeks of study informed consent and or if the subject has not fully recovered from the surgery within 4 weeks of informed consent History of major gastrointestinal surgery History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial Currently active, clinically significant cardiovascular disease Known active intravenous drug or alcohol abuse or use of other drugs of abuse Has any contraindication as mentioned in the recent Keytruda, Highlights of Prescribing Information (pembrolizumab)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CJRB-101 with pembrolizumab<br>Phase 1 includes patients with selected types of advanced or metastatic cancers. Patients will be given with either low or high dose levels of CJRB-101 in combination with pembrolizumab. Phase 2 includes patients with selected types of advanced or metastatic cancers. Patients will be given with the CJRB-101 dose selected from Phase 1 in combination with pembrolizumab. | Drug: CJRB-101<br>* In Phase 1, one or two capsules of CJRB-101 will be given every day. In Phase 2, the CJRB-101 dose selected from Phase 1 will be given every day.<br>Drug: Pembrolizumab injection<br>* 200 mg given by intravenous (IV) infusion once every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [Phase 1&2] Tolerability and Safety: Incidence of Adverse Events | Assessed per CTCAE v5.0 | Maximum 2 years | 
| [Phase 2] Efficacy | ORR | Maximum 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [Phase 1&2] Effects of therapy on the microbiome biomarkers - Stool | Fecal samples will be used to analyze gut microbiome using amplicon sequencing and/or whole-genome shotgun metagenomic sequencing. | Maximum 2 years | 
| [Phase 1&2] Effects of therapy on the pharmacodynamic biomarkers - Blood | Blood samples will be analyzed for the immune profiling and biomarkers of therapy effect. | Maximum 2 years | 
| [Phase 1&2] Effects of therapy on the pharmacodynamic biomarkers - Tumor | Tumor tissue samples will be analyzed for immune profiling and evaluated for prediction of therapy effectiveness. | Maximum 2 years | 
| Objective Response Rate (ORR) | Antitumor effect is assessed through tumor image and tumor lesion per RECIST v1.1. | Maximum 2 years | 
| Disease Control Rate (DCR) | Antitumor effect is assessed through tumor image and tumor lesion per RECIST v1.1. | Maximum 2 years | 
| Duration Of Response (DOR) | Antitumor effect is assessed through tumor image and tumor lesion per RECIST v1.1. | Maximum 2 years | 
| Progression Free Survival (PFS) | Antitumor effect is assessed through tumor image and tumor lesion per RECIST v1.1. | Maximum 2 years | 
| Overall survival (OS) |  | Maximum 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Live Biotherapeutic Product, Keytruda, CJRB-101, metastatic, Immune checkpoint inhibitor, Pembrolizumab, CJB-101-01, anti-PD1, anti-PDL1