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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; NSCLC; Metastatic Cancer; Advanced Solid Tumor; Advanced Cancer; HNSCC
• Intervention / Treatment: Drug: CJRB-101; Drug: Pembrolizumab injection

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Hyun Kim; Phone Number: +82-2-6078-3456; Email: clinical.development@cj.net

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
    • Contact: Hyun Kim; Phone Number: 82-2-60783456; Email: clinical.development@cj.net
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Contact: Hyun Kim; Phone Number: 82260783456; Email: clinical.development@cj.net
• United States
  • California
    • Irvine, California, United States, 92697
      • Recruiting
      • University of California, Irvine
      • Contact: Misako Nagasaka, MD, PhD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • Recruiting
      • University of Pittsburgh
      • Contact: Diwakar Davar, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide informed consent
2. ≥18 years of age at the time of signing the informed consent form
3. Pathologically documented histological or cytological evidence of NSCLC, HNSCC, or melanoma.
4. Has at least 1 measurable target lesion per RECIST v1.1 that has not been resected/biopsied/or irradiated before enrollment in the study
5. 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

6. ICI treatment-naive subjects must meet the following criteria:

   1. 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%]
   2. HNSCC: Subjects with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [CPS ≥20]
   3. Melanoma: Irrespective of PD-L1 result and BRAF V600 mutation
   4. 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.

7. ICI treatment-refractory subjects as defined by the following criteria:

   1. Has received at least 2 cycles of anti-PD-(L)1 therapy either as monotherapy or in combination
   2. Has demonstrated disease progression after ICI treatment by RECIST v1.1
   3. Has received less than three lines of systemic therapy for metastatic tumor
8. ECOG performance status of 0 or 1
9. Be willing to provide archival tissue or fresh biopsy
10. Have adequate organ function
11. All Grade 3 or greater AEs resolved earlier to Grade 2 or less

Exclusion Criteria:

1. Cancer type and genomic tumor aberrations:

   1. NSCLC subjects with EGFR or ALK genomic tumor aberrations
   2. HNSCC subjects with nasopharyngeal cancer
2. 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
3. With uncontrolled or untreated brain metastasis or leptomeningeal disease
4. Active autoimmune disease that has required systemic treatment in the past 2 years
5. Received a fecal transplant
6. Concurrent participation in another interventional clinical study or use of another investigational agent within 30 days of study consent
7. Contraindication to IV contrast that cannot be managed with pre-medication
8. Female subjects who are pregnant or breastfeeding
9. Male subjects who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy
10. Has a known inability for oral intake of capsules
11. Has received a live vaccine within 4 weeks of start of the study treatment
12. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy
13. Has received whole blood transfusion, blood component transfusion, or colony stimulating factors within 1 week prior to the 1st dose of study treatment
14. In the judgment of the investigator, subjects unlikely to comply with study procedures, restrictions and requirements
15. Has active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids
16. Have allergy to clindamycin, erythromycin, and ampicillin
17. Has signs and symptoms of colitis at screening
18. 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)
19. 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.)
20. 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.)
21. Known history of HIV infection
22. History of active inflammatory bowel disease with diarrhea believed to be caused by active inflammatory bowel disease in the past 12 months
23. 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
24. History of major gastrointestinal surgery
25. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial
26. Currently active, clinically significant cardiovascular disease
27. Known active intravenous drug or alcohol abuse or use of other drugs of abuse
28. Has any contraindication as mentioned in the recent Keytruda, Highlights of Prescribing Information (pembrolizumab)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CJ Bioscience, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: March 12, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Pembrolizumab; Keytruda; metastatic; Immune checkpoint inhibitor; anti-PD1; anti-PDL1; Live Biotherapeutic Product; CJRB-101; CJB-101-01
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Neoplasms; Neoplasms, Second Primary; Neoplasm Metastasis; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: CJB-101-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No