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

Sponsor

CJ Bioscience, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05877430

Collaborator

(none)

160

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
NSCLC HNSCC Melanoma Metastatic Cancer Advanced Solid Tumor Advanced Cancer	Drug: CJRB-101 Drug: Pembrolizumab injection	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Oct 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CJRB-101 with pembrolizumab 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 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. Drug: Pembrolizumab injection 200 mg given by intravenous (IV) infusion once every 3 weeks

Arm

Intervention/Treatment

Experimental: CJRB-101 with pembrolizumab

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

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.

Drug: Pembrolizumab injection

200 mg given by intravenous (IV) infusion once every 3 weeks

Outcome Measures

Primary Outcome Measures

[Phase 1&2] Tolerability and Safety: Incidence of Adverse Events [Maximum 2 years]
Assessed per CTCAE v5.0
[Phase 2] Efficacy [Maximum 2 years]
ORR

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)