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

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, ormelanoma.

4. Has at least 1 measurable target lesion per RECIST v1.1 that has not beenresected/biopsied/or irradiated before enrollment in the study

5. Diagnosis of locally advanced unresectable or metastatic NSCLC, HNSCC, or melanomain subjects who are ICI treatment-naive or relapsed/refractory, including PD-1/PD-L1inhibitors

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

7. NSCLC: Subjects with metastatic or with unresectable, recurrent NSCLC whosetumors must have no EGFR or ALK genomic aberrations and express PD-L1 [TPS≥50%]

8. HNSCC: Subjects with metastatic or with unresectable, recurrent HNSCC whosetumors express PD-L1 [CPS ≥20]

9. Melanoma: Irrespective of PD-L1 result and BRAF V600 mutation

10. Subjects has not received prior systemic treatment for their metastatic tumor.Subjects who received adjuvant or neoadjuvant therapy are eligible if theadjuvant/neoadjuvant therapy was completed at least 6 months before thedevelopment of metastatic disease.

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

12. Has received at least 2 cycles of anti-PD-(L)1 therapy either as monotherapy orin combination

13. Has demonstrated disease progression after ICI treatment by RECIST v1.1

14. Has received less than three lines of systemic therapy for metastatic tumor

15. ECOG performance status of 0 or 1

16. Be willing to provide archival tissue or fresh biopsy

17. Have adequate organ function

18. All Grade 3 or greater AEs resolved earlier to Grade 2 or less

Exclusion Criteria:

1. Cancer type and genomic tumor aberrations:

2. NSCLC subjects with EGFR or ALK genomic tumor aberrations

3. HNSCC subjects with nasopharyngeal cancer

4. For ICI refractory/relapsed subjects: Immune related AEs ≥Grade 3 that led todiscontinuation of prior immune-modulatory agents including PD-1/PD-L1 inhibitors

5. With uncontrolled or untreated brain metastasis or leptomeningeal disease

6. Active autoimmune disease that has required systemic treatment in the past 2 years

7. Received a fecal transplant

8. Concurrent participation in another interventional clinical study or use of anotherinvestigational agent within 30 days of study consent

9. Contraindication to IV contrast that cannot be managed with pre-medication

10. Female subjects who are pregnant or breastfeeding

11. Male subjects who are unwilling or unable to use an acceptable method of birthcontrol to avoid pregnancy

12. Has a known inability for oral intake of capsules

13. Has received a live vaccine within 4 weeks of start of the study treatment

14. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressivetherapy

15. Has received whole blood transfusion, blood component transfusion, or colonystimulating factors within 1 week prior to the 1st dose of study treatment

16. In the judgment of the investigator, subjects unlikely to comply with studyprocedures, restrictions and requirements

17. Has active interstitial lung disease (ILD)/pneumonitis or a history ofILD/pneumonitis requiring treatment with systemic steroids

18. Have allergy to clindamycin, erythromycin, and ampicillin

19. Has signs and symptoms of colitis at screening

20. Infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before study treatment (Note: Antiviral therapy is permitted for subjectswith chronic HBV or HCV infection)

21. 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 bemanaged per treatment guidelines. Subjects receiving antivirals at screening shouldhave been treated for > 2 weeks before study treatment.)

22. With active hepatitis C (Note: Subjects with a negative HCV antibody test atscreening 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 forsubjects testing positive for HCV antibody. Subjects receiving antivirals atscreening should have been treated for > 2 weeks before study treatment.)

23. Known history of HIV infection

24. History of active inflammatory bowel disease with diarrhea believed to be caused byactive inflammatory bowel disease in the past 12 months

25. Major surgery for any reason, except diagnostic biopsy, within 4 weeks of studyinformed consent and or if the subject has not fully recovered from the surgerywithin 4 weeks of informed consent

26. History of major gastrointestinal surgery

27. History or current evidence of any condition, therapy, or laboratory abnormalitythat might confound the results of the trial

28. Currently active, clinically significant cardiovascular disease

29. Known active intravenous drug or alcohol abuse or use of other drugs of abuse

30. Has any contraindication as mentioned in the recent Keytruda, Highlights ofPrescribing Information (pembrolizumab)