A Phase 1 Study to Evaluate TGI-6 in Subjects With Locally Advanced/Metastatic Solid Tumors

Inclusion Criteria:

1. Male or female subjects age ≥18 years at the time of informed consent.
2. Phase 1a: Subjects with histologically or cytologically diagnosed unresectable locallyadvanced/metastatic CRC. Or subjects with confirmed B7-H6-positive unresectablelocally advanced/metastatic solid tumors, mainly but not limited to TNBC, HCC, HNSCC,SCLC, OC, GC, pancreatic cancer, and melanoma. Phase 1b Cohort 1: Subjects must have pathologically documented, definitivelydiagnosed unresectable locally advanced and/or metastatic CRC. Phase 1b Cohort 2: Subjects must have pathologically documented, definitivelydiagnosed unresectable locally advanced and/or metastatic solid tumors withB7-H6-positive, mainly but not limited to TNBC, HCC, HNSCC, SCLC, OC, GC, pancreaticcancer, and melanoma.
3. Phase 1a or Phase1b Cohort 2: Subjects should have progressed despite all standardtherapy or be intolerant of all standard therapy, or for whom no standard therapyexists. (Standard therapies are defined as treatments recommended by local guidelines,including, but not limited to, chemotherapy, radiation, target therapies based onmutation status, immunotherapy, and surgery in general).
4. All subjects except subjects with CRC must agree to the collection of tumor samplesfor confirmation of B7-H6 expression status in a central lab.
5. Subjects in Phase 1a must have at least one evaluable lesion as defined by ResponseEvaluation Criteria in Solid Tumors (RECIST) v1.1. Subjects in Phase 1b must haveleast one measurable lesion as defined per RECIST v1.1 which has not receivedradiotherapy (or progressive disease after radiotherapy).
6. ECOG PS (Appendix 5) of 0~2.
7. Life expectancy ≥3 months.
8. Subjects have sufficient baseline organ function and laboratory data .
9. Woman of childbearing potential must have a negative serum pregnancy test within 7days prior to treatment.
10. Female subjects of childbearing potential or male subjects with a partner ofchildbearing potential must agree to use effective contraception at the time ofinformed consent and continuing through the study until 6 months after the last doseof TGI-6.

Exclusion Criteria:

1. Subject with known active central nervous system (CNS) primary tumor or metastases.
2. History of intercurrent severe chronic or active infections.
3. Has a history of active autoimmune diseases .
4. Has a history of symptomatic interstitial lung disease.
5. Toxicities of prior therapies have not been resolved to Grade ≤1 or baseline as perNCI-CTCAE v5.0, except for alopecia, skin hyperpigmentation, Grade 2 neuropathy andGrade 2 endocrinopathy that is well controlled by replacement therapy.
6. Subjects with severe or uncontrolled cardiovascular disorder requiring treatment.
7. Prior allogenic or autologous bone marrow transplantation or other solid organtransplantation.
8. Has a known additional malignancy that is progressing or has required active treatmentwithin the past 3 years .
9. Evidence of clinically significant immunosuppression .
10. Presence of uncontrolled pleural effusion, pericardial effusion or ascites requiringrecurrent drainage procedures .
11. Previously treated with the following anti-tumor therapy (prior to the first dose ofTGI-6):

1. Previous treated with any B7-H6-targeting therapy. 2) Chemotherapy, target therapy,immunotherapy, or other anticancer therapy within 28 days or 5 half-lives, whichever isshorter, prior to the first dose of study treatment, except:

1. Washout period for nitrosoureas or mitomycin is ≤6 weeks.
2. ≤5 half-lives or 2 weeks (whichever is longer) for fluoropyrimidines or small-moleculetargeted agents.
3. Washout period for herbal therapy with anticancer indications is ≤2 weeks. 3) Priorradiotherapy ≤4 weeks prior to the first dose of study treatment, with the exceptionof a single fraction of radiotherapy for the purposes of palliation, which ispermitted.

4. Subject participated in any other clinical study and has received aninvestigational product within 28 days prior to the first dose of TGI-6.exists. (Standard therapies are defined as treatments recommended by local guidelines,
including, but not limited to, chemotherapy, radiation, target therapies based on
mutation status, immunotherapy, and surgery in general).
 

4. All subjects except subjects with CRC must agree to the collection of tumor samples
for confirmation of B7-H6 expression status in a central lab.
 
5. Subjects in Phase 1a must have at least one evaluable lesion as defined by Response
Evaluation Criteria in Solid Tumors (RECIST) v1.1. Subjects in Phase 1b must have
least one measurable lesion as defined per RECIST v1.1 which has not received
radiotherapy (or progressive disease after radiotherapy).
 
6. ECOG PS (Appendix 5) of 0~2.
 
7. Life expectancy ≥3 months.
 
8. Subjects have sufficient baseline organ function and laboratory data .
 
9. Woman of childbearing potential must have a negative serum pregnancy test within 7
days prior to treatment.
 
10. Female subjects of childbearing potential or male subjects with a partner of
childbearing potential must agree to use effective contraception at the time of
informed consent and continuing through the study until 6 months after the last dose
of TGI-6.
 
Exclusion Criteria:
 
11. Subject with known active central nervous system (CNS) primary tumor or metastases.
 
12. History of intercurrent severe chronic or active infections.
 
13. Has a history of active autoimmune diseases .
 
14. Has a history of symptomatic interstitial lung disease.
 
15. Toxicities of prior therapies have not been resolved to Grade ≤1 or baseline as per
NCI-CTCAE v5.0, except for alopecia, skin hyperpigmentation, Grade 2 neuropathy and
Grade 2 endocrinopathy that is well controlled by replacement therapy.
 
16. Subjects with severe or uncontrolled cardiovascular disorder requiring treatment.
 
17. Prior allogenic or autologous bone marrow transplantation or other solid organ
transplantation.
 
18. Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years .
 
19. Evidence of clinically significant immunosuppression .
 
20. Presence of uncontrolled pleural effusion, pericardial effusion or ascites requiring
recurrent drainage procedures .
 
21. Previously treated with the following anti-tumor therapy (prior to the first dose of
TGI-6):
 

1. Previous treated with any B7-H6-targeting therapy. 2) Chemotherapy, target therapy,
immunotherapy, or other anticancer therapy within 28 days or 5 half-lives, whichever is
shorter, prior to the first dose of study treatment, except:
 

1. Washout period for nitrosoureas or mitomycin is ≤6 weeks.
 
2. ≤5 half-lives or 2 weeks (whichever is longer) for fluoropyrimidines or small-molecule
targeted agents.
 
3. Washout period for herbal therapy with anticancer indications is ≤2 weeks. 3) Prior
radiotherapy ≤4 weeks prior to the first dose of study treatment, with the exception
of a single fraction of radiotherapy for the purposes of palliation, which is
permitted.
 

4. Subject participated in any other clinical study and has received an
investigational product within 28 days prior to the first dose of TGI-6.

12. Has received systematic immunomodulatory drugs within 14 days before the firstdose of study drug, such as thymosin, IL-2, and interferon (IFN).
13. Has received a live vaccine within 4 weeks prior to the first dose of study drug.
14. Has a recent major surgery within 4 weeks prior to the first dose of study drug oris expected to undergo major surgery during the study.
15. Subject requiring anticoagulant treatment which cannot be safely interrupted, ifmedically needed for a study procedure (e.g., biopsy) based on the opinion of theInvestigator.
16. Has a known psychiatric or substance abuse disorder that would interfere with thesubject's ability to cooperate with the requirements of the study.
17. Pregnancy or lactation. 18. Has known hypersensitivity to either the drugsubstances or inactive ingredients in the drug product.
18. Pre-existing other serious medical conditions, familial or endemic disease that,in the opinion of the investigator, will interfere with planned staging, treatment,and follow-up, subject compliance, or will place the subject at high risk fortreatment-related complications.
19. Subjects who are unwilling or unable to comply with study procedures and studyrestrictions, or in the judgment of the investigator, would make the subjectinappropriate for entry into this study.