A Phase 1/2 Study of OBI-992 in Subjects With Advanced Solid Tumors

A Phase 1/2, Open-Label, Dose-Escalation and Cohort-Expansion Study Evaluating the Safety, Pharmacokinetics, and Therapeutic Activity of OBI-992 in Subjects With Advanced Solid Tumors

This is a 2-part trial: Part A (Dose Escalation) is designed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of OBI-992 (Anti-TROP2 antibody drug conjugate, anti-TROP2 monoclonal antibody-cleavable peptide linker-exatecan) as monotherapy. Part B (Cohort Expansion) is intended to further characterize the safety and preliminary clinical activity profile of the RP2D of OBI-992 in subjects with advanced solid tumors.

Inclusion Criteria:

1. Male or female subjects, 18 years of age or older at the time of consent

2. Provide written informed consent prior to performing any study-related procedure

3. Histologically or cytologically confirmed subjects with metastatic or advanced solid tumor that is not curable with local therapies

4. Subjects must have been treated with established standard-of-care therapy, or physicians have determined that such established therapy is not sufficiently efficacious, or subjects have declined to receive standard-of-care therapy. In the latter case, the informed consent must state the effective therapies the subject is declining.

5. Measurable disease (i.e., at least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1])

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

7. Adequate organ function defined as:

   a. Hepatic: i. Serum alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN), ≤5 × ULN in the presence of liver metastases ii. Serum aspartate aminotransferase (AST) ≤3 × ULN, ≤5 × ULN in presence of liver metastases iii. Serum bilirubin ≤1.5 × ULN (unless due to Gilbert's syndrome or hemolysis) b. Renal: i. Creatinine clearance >50 mL/minute using Cockcroft Gault equation c. Hematologic: i. Absolute neutrophil count ≥1,500/μL ii. Platelets ≥100,000/μL iii. Hemoglobin ≥8 g/dL

8. Subjects are willing and able to comply with all protocol-required assessments, visits, and procedures, including pretreatment tumor biopsy. Archival tumor biopsies are acceptable at baseline.

9. Females of childbearing potential must have negative serum pregnancy test prior to starting study therapy and agree to use a reliable form of contraceptive during the study treatment period and for at least 120 days following the last dose of study drug. Subject not of childbearing potential (i.e., permanently sterilized, postmenopausal) can be included in the trial. Postmenopausal is defined as 12 months with no menses without an alternative medical cause. Male subjects must agree to use an adequate method of contraception during the study treatment period and for at least 120 days following the last dose of study drug.

10. Cannot be breast feeding

11. Subjects with human immunodeficiency virus (HIV) infection are eligible if CD4+ Tcell counts ≥ 350 cells/μL; subjects on anti-retroviral therapy (ART) should be on an established dose for at least 4 weeks and have an HIV viral load less than 200 copies/mL prior to enrollment.

12. Subjects with serological evidence of chronic hepatitis B virus (HBV) infection are eligible if they have an HBV viral load below the limit of quantification with or without concurrent viral suppressive therapy.

13. Subjects with a history of hepatitis C virus (HCV) infection can be under curative antiviral treatment and have a viral load below the limit of quantification.

14. Subjects in Part B (Cohort-Expansion) - must have one of the following tumor types to be enrolled in the respective cohort:

    • Cohort 1: Non-small cell lung cancer (NSCLC)

      o Pathologically confirmed subjects with metastatic NSCLC with or without actionable genomic alterations.

    • Cohort 2: Small cell lung cancer (SCLC)

    • Cohort 3: Gastric cancer

Exclusion Criteria:

1. Less than 3 weeks from prior cytotoxic chemotherapy or radiation therapy; and less than 5 half-lives or 3 weeks, whichever is shorter, from prior biologic therapies, prior to the first dose of OBI-992
2. Has undergone a major surgical procedure (as defined by the Investigator) or significant traumatic injury within 28 days prior to the first dose of OBI-992
3. Sensory or motor neuropathy of Grade 2 or greater
4. Subjects with a history of solid organ transplant
5. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Grade 0 or 1 (using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0), except for alopecia and laboratory values listed in the inclusion criteria
6. Corrected QT interval (QTcF) prolongation to >470 msec based on the average of the screening 12-lead ECGs
7. Known hypersensitivity to OBI-992 or its excipients
8. Has known untreated central nervous system (CNS) metastases. Subjects with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period
9. Has significant clinical cardiac abnormality (e.g., clinical heart failure or unstable angina)
10. Any medical comorbidity that is life-threatening or, in the opinion of the Investigator, renders the subject unsuitable for participation in a clinical trial due to possible noncompliance, would place the subject at an unacceptable risk (e.g. Interstitial lung disease (ILD)) and/or potential to affect interpretation of results of the study.
11. Subjects in Part B (Phase 2 Cohort Expansion) may not have had prior therapy with an approved or investigational TROP2 ADC (prior TROP2 ADC therapy allowed during dose escalation)
12. Is receiving any concurrent prohibited medications