Overview

The study drug TRX-920 Oral Gel contains SN38, an active metabolite of Irinotecan (CPT-11), which is a widely prescribed anti-cancer drug that has been approved in many countries for the treatment of colorectal and pancreatic cancer. TRX-920 is the oral gel formulation that directly contains SN38 instead of Irinotecan. A series of biology and animal studies have demonstrated that the TRX-920 Oral Gel could inhibit tumor growth with fewer side effects compared to Irinotecan.

Eligibility

Inclusion Criteria:

        Subjects must meet all of the following criteria to be eligible for enrollment in the
        study:
          1. Signed and dated informed consent form
          2. Histologically and cytologically confirmed advanced solid tumor malignancies that are
             refractory to standard therapy or have no accepted standard therapy.
          3. Solid tumors that are measurable or evaluable as per Response Evaluation Criteria in
             Solid Tumors (RECIST v1.1). Target lesions that have been previously irradiated will
             not be considered measurable (lesion).
          4. Female or male, 18 years of age or older.
          5. ECOG performance status 0 or 1.
          6. QTcF ≤ 480 ms at screening.
        Exclusion Criteria:
          1. Patients with homozygous or compound heterozygous genotypes for UGT1A1*28 and *6
             alleles (e.g., 28/28, 6/6, 6/28).
          2. Clinically significant comorbidity such as unstable angina, congestive heart failure
             (NYHA Grade III or IV), uncontrolled hypertension (>160/100 mmHg despite optimal
             medical treatment), chronic obstructive pulmonary disease (COPD) with frequent
             exacerbations, refractory asthma, inflammatory bowel disease or intestinal
             obstruction.
          3. Acute myocardial infraction or cerebrovascular accident (CVA) within 6 months prior
             the first dose of study drug.
          4. Central nervous system (CNS) metastasis or seizure disorder due to underlying
             malignancy except those who have been treated and have stable CNS metastases or are
             asymptomatic.
          5. AIDS-defining opportunistic infections within the past 12 months.
          6. HBV infection (positive HBsAg) except for carrier of inactive HBV as defined by
             negative HBeAg with normal ALT and HBV DNA < 2,000 IU/mL or HCV infection (positive
             anti-HCV antibody) except for those with undetectable HCV RNA.
          7. Inadequate bone marrow reserve, hepatic or renal function as defined by any of the
             following laboratory values:
               1. absolute neutrophil count (ANC) < 1500/µL
               2. platelet count < 90,000/µL
               3. hemoglobin < 9 g/dL
               4. total bilirubin > 1.5*the upper limit of normal (ULN)
               5. aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3ULN if no
                  hepatic metastases are present; > 5ULN if hepatic metastases are present
               6. Non-indexed eGFR < 60 mL/min (formula in Appendix 4)
          8. Toxicities resulting from prior therapy or surgical procedures not yet resolved to ≤
             NCI CTCAE v5.0 Grade 1 with the exception of alopecia, skin hyperpigmentation or
             hypopigmentation or grade 2 toxicity with prior approval of the Medical Monitor.
          9. Major surgical procedures (as defined by Investigator) within 4 weeks prior to the
             first dose of study drug or any ongoing post-operative complications.
         10. Receiving any radiotherapy within 3 months
         11. Receiving any (investigational or approved) anti-cancer therapy (including
             chemotherapy or targeted therapy) within 28 days or 5 half-lives (whichever is longer)
             prior to the first dose of study drug
         12. A history of apparent allergic reactions to irinotecan injection (dosed with prior
             treatment with prophylactic drug)
         13. If female, is pregnant or breastfeeding
         14. If men or women with childbearing potential, unwilling to use effective contraceptive
             methods during the study and for at least 3 months (men) or 1 month (women) after the
             last dose of study drug. Effective contraceptive methods include implants,
             injectables, combined oral contraceptives, intra-uterine devices (IUDs), sexual
             abstinence, surgical sterilization, or a partner who is sterile.
         15. Receiving live attenuated vaccine within 28 days prior to the first dose of study
             drug.
         16. Life expectancy < 3 months.
         17. Other prior or ongoing condition(s) that, in the opinion of the investigator, could
             affect the safety of the subject, compromise the subject's ability to comply with the
             study requirements or impair the assessment of study results.