Overview

This is a 2-part trial: Part A (Dose Escalation) is designed to establish the maximum tolerated dose (MTD) and putative recommended phase 2 dose of OBI-902 (study drug) as monotherapy. Part B (Cohort Expansion) is intended to determine the optimal RP2D and further characterize the safety and preliminary clinical activity profile of the OBI-902 RP2D in participants with advanced solid tumors.

Eligibility

Inclusion Criteria:

1. Male or female participants, 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 participants with metastatic or advanced solid tumor that is not curable with local therapies
4. Participants must have been treated with established standard-of-care therapy, or physicians have determined that such established therapy is not sufficiently efficacious, or patients have declined to receive standard-of-care therapy. In the latter case, the source documentation must state the effective therapies the participant is declining.
5. Measurable disease (i.e., at least one measurable lesion per RECIST 1.1)
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Adequate organ function defined as:
   1. Hepatic:
   2. Serum ALT ≤3 × upper limit of normal (ULN), ≤5 × ULN in the presence of liver metastases
   3. Serum AST ≤3 × ULN, ≤5 × ULN in presence of liver metastases

     ii. Serum bilirubin ≤1.5 × ULN (unless due to Gilbert's syndrome (typically elevated
     total bilirubin of 1-5 mg/dL with a normal direct bilirubin) or hemolysis)
     b. Creatinine clearance >60 mL/minute using Modification of Diet in Renal Disease
     equation
     c. Hematologic:
     i. ANC ≥1,500/µL (>1,200/µL in Duffy antigen-null participants)
     ii. Platelets ≥100,000/µL
     iii. Hemoglobin ≥8 g/dL

8. Participants must be willing and able to comply with all protocol-required

     assessments, visits, and procedures, including pretreatment tumor biopsy. Archival
     tumor biopsies are acceptable at baseline. Each biopsy slide shall include ≥ 100
     tumor cells.

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 7 months following the last dose of study
     drug.

10. Participants 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 participants must agree to
     use an adequate method of contraception during the study treatment period and for at
     least 4 months following the last dose of study drug.

11. Cannot be breast feeding.

12. Participants with human immunodeficiency virus (HIV) infection are eligible if CD4+

     T-cell counts ≥350 cells/μL; participants on 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.

13. Participants with serological evidence of chronic HBV infection are eligible if they

     have an HBV viral load below the limit of quantification with or without concurrent
     viral suppressive therapy.

14. Participants with a history of HCV infection can be under curative antiviral

treatment and have a viral load below the limit of quantification.

15. Participants in Part B (Cohort Expansion) - must have one of the following tumor

types to be enrolled in the respective cohort:

• Cohort 1: Relapsed/refractory HER2-negative BC
• Cohort 2: Relapsed/refractory EC
• Cohort 3: Relapsed/refractory intra- or extrahepatic CCA

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-902.
2. Participants that have undergone a major surgical procedure (as defined by the Investigator) or significant traumatic injury within 28 days prior to the first dose of OBI-902.
3. Sensory or motor neuropathy of Grade 2 or greater.
4. Participants with a history of solid organ transplant. Corneal transplant without immunosuppressive therapy is allowed.
5. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Grade 0 or 1 (using NCI CTCAE version 5.0), except for alopecia and laboratory values listed in the inclusion criteria.
6. Receipt of any prior therapy targeting TROP2. (Phase 2 only)
7. Corrected QT interval (QTcF) prolongation to >470 msec based on the average of the screening 12-lead ECGs
8. Known hypersensitivity to OBI-902 or its excipients.
9. Participants with known untreated central nervous system (CNS) metastases. Participants 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.
10. Participants with significant clinical cardiac abnormality (e.g., clinical heart failure or unstable angina).
11. Any medical comorbidity that is life-threatening or, in the opinion of the Investigator, renders the participant unsuitable for participation in a clinical trial due to possible noncompliance, would place the participant at an unacceptable risk and/or potential to affect interpretation of results of the study.
12. Is receiving any concurrent prohibited medications as listed in OBI-902-001 clinical protocol.