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

NCT06480240 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: OBI-992-001
• Study Type: interventional
• Target: 117
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (7)

• Safety and tolerability of OBI-992: incidence of adverse events, serious adverse events, and laboratory abnormalities

  To determine the safety and tolerability of OBI-992 when administered to subjects with advanced solid tumors, based on adverse events (AEs), serious adverse events (SAEs) and laboratory abnormalities graded by NCI CTCAE v5.0

  Duration of study, up to 2 years and 2 months

• Maximum tolerated dose and recommended Phase 2 dose of OBI-992

  To determine the maximum tolerated dose (MTD) and optimal recommended phase 2 dose (RP2D) of OBI-992

  Duration of study, up to 2 years and 2 months

• Preliminary clinical activity profile - objective response rate (ORR)

  Percentage of subjects in the as-treated population with objective response according to response evaluation criteria in solid tumors (RECIST v.1.1)

  Duration of study, up to 2 years and 2 months

• Preliminary clinical activity profile - clinical benefit rate (CBR)

  Percentage of subjects in the as-treated population with clinical benefit according to response evaluation criteria in solid tumors (RECIST v.1.1)

  Duration of study, up to 2 years and 2 months

• Preliminary clinical activity profile - duration of response (DOR)

  Percentage of subjects in the as-treated population with response according to response evaluation criteria in solid tumors (RECIST v.1.1)

  Duration of study, up to 2 years and 2 months

• Preliminary clinical activity profile - disease control rate (DCR)

  Percentage of subjects in the as-treated population with disease control according to response evaluation criteria in solid tumors (RECIST v.1.1)

  Duration of study, up to 2 years and 2 months

• Preliminary clinical activity profile - progression-free survival

  Percentage of subjects in the as-treated population with progression-free survival according to response evaluation criteria in solid tumors (RECIST v.1.1)

  Duration of study, up to 2 years and 2 months

Secondary Outcomes (6)

• Immunogenicity of OBI-992: anti-drug antibodies (ADAs)

  Duration of study, up to 2 years and 2 months

• Serum pharmacokinetics (PK): Peak Plasma Concentration (Cmax) of OBI-992 and its active metabolite

  Duration of study, up to 2 years and 2 months

• Serum pharmacokinetics (PK): area under the concentration-time curve (AUC) of OBI-992 and its active metabolite

  Duration of study, up to 2 years and 2 months

• Serum pharmacokinetics (PK): half-life (T1/2) of OBI-992 and its active metabolite

  Duration of study, up to 2 years and 2 months

• Serum pharmacokinetics (PK): clearance (CL) of OBI-992 and its active metabolite

  Duration of study, up to 2 years and 2 months

Study Arms (10)

Phase 1 Dose Escalation - Cohort 1

EXPERIMENTAL

OBI-992 at dose level 1 mg/kg, Q3W

Drug: OBI-992

Phase 1 Dose Escalation - Cohort 2

EXPERIMENTAL

OBI-992 at dose level 2 mg/kg, Q3W

Drug: OBI-992

Phase 1 Dose Escalation - Cohort 3

EXPERIMENTAL

OBI-992 at dose level 4 mg/kg, Q3W

Drug: OBI-992

Phase 1 Dose Escalation - Cohort 4

EXPERIMENTAL

OBI-992 at dose level 6 mg/kg, Q3W

Drug: OBI-992

Phase 1 Dose Escalation - Cohort 5

EXPERIMENTAL

OBI-992 at dose level 8 mg/kg, Q3W

Drug: OBI-992

Phase 1 Dose Escalation - Cohort 6

EXPERIMENTAL

OBI-992 at dose level 10 mg/kg, Q3W

Drug: OBI-992

Phase 2 Cohort Expansion - Cohort 1a

EXPERIMENTAL

Non-small cell lung cancer indication cohort - Randomized dose optimization cohort. Dose level to be determined by the Safety Review Committee based on data available.

Drug: OBI-992

Phase 2 Cohort Expansion - Cohort 1b

EXPERIMENTAL

Non-small cell lung cancer indication cohort - Randomized dose optimization cohort. Dose level to be determined by the Safety Review Committee based on data available.

Drug: OBI-992

Phase 2 Cohort Expansion - Cohort 2

EXPERIMENTAL

Small cell lung cancer indication cohort - OBI-992 dosed at putative recommended phase 2 dose.

Drug: OBI-992

Phase 2 Cohort Expansion - Cohort 3

EXPERIMENTAL

Gastric cancer indication cohort - OBI-992 dosed at putative recommended phase 2 dose.

Drug: OBI-992

Interventions

OBI-992 DRUG

OBI-992 is an antibody-drug conjugate

Phase 1 Dose Escalation - Cohort 1; Phase 1 Dose Escalation - Cohort 2; Phase 1 Dose Escalation - Cohort 3; Phase 1 Dose Escalation - Cohort 4; Phase 1 Dose Escalation - Cohort 5; Phase 1 Dose Escalation - Cohort 6; Phase 2 Cohort Expansion - Cohort 1a; Phase 2 Cohort Expansion - Cohort 1b; Phase 2 Cohort Expansion - Cohort 2; Phase 2 Cohort Expansion - Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, 18 years of age or older at the time of consent
• Provide written informed consent prior to performing any study-related procedure
• Histologically or cytologically confirmed subjects with metastatic or advanced solid tumor that is not curable with local therapies
• 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.
• Measurable disease (i.e., at least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\])
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• 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
• 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.
• 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.
• Cannot be breast feeding
• 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.
• 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.
• 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.
• Subjects in Part B (Cohort-Expansion) - must have one of the following tumor types to be enrolled in the respective cohort:

You may not qualify if:

• 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
• 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
• Sensory or motor neuropathy of Grade 2 or greater
• Subjects with a history of solid organ transplant
• Corrected QT interval (QTcF) prolongation to \>470 msec based on the average of the screening 12-lead ECGs
• Known hypersensitivity to OBI-992 or its excipients
• 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
• Has significant clinical cardiac abnormality (e.g., clinical heart failure or unstable angina)
• 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.
• 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)
• Is receiving any concurrent prohibited medications

Sponsors & Collaborators

• OBI Pharma, Inc: lead

Study Sites (8)

California Clinical Trials Medical Group (CCTMG)

Glendale, California, 91206, United States

Location

Scripps Green Hospital

La Jolla, California, 92037, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Taipei Tzu Chi Hospital

New Taipei City, Xindian District, 231036, Taiwan

Location

Taipei Medical University - Shuang Ho Hospital

New Taipei City, Zhonghe District, 23561, Taiwan

Location

Related Publications (1)

• Shia CS, Wen SN, Hsu RY, Tu JS, Chang HW, Weng HC, Yang JJ, Chiang MF, Tsao YH, Lu CH, Chen YH, Wu YC, Chen YC, Li WF, Huang TY, Lai MT. Preclinical Pharmacokinetic, Pharmacodynamic, and Safety Profile of OBI-992: A Novel TROP2-Targeted Antibody-Drug Conjugate. Mol Cancer Ther. 2025 Dec 2;24(12):1938-1947. doi: 10.1158/1535-7163.MCT-24-1176.

  PMID: 40762235 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation: Interval (3+3) model Cohort expansion: parallel-group with randomized dosage optimization

Study Record Dates

• First Submitted: June 18, 2024
• First Posted: June 28, 2024
• Study Start: June 12, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: August 8, 2025

Record last verified: 2025-08

Locations

US (6); TW (2)