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
Overview
- Phase
- Phase 1
- Intervention
- OBI-992
- Conditions
- Advanced Solid Tumor
- Sponsor
- OBI Pharma, Inc
- Enrollment
- 117
- Locations
- 8
- Primary Endpoint
- Preliminary clinical activity profile - disease control rate (DCR)
- Status
- Active, not recruiting
- Last Updated
- 8 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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
- •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
- •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.
Arms & Interventions
Phase 1 Dose Escalation - Cohort 1
OBI-992 at dose level 1 mg/kg, Q3W
Intervention: OBI-992
Phase 1 Dose Escalation - Cohort 2
OBI-992 at dose level 2 mg/kg, Q3W
Intervention: OBI-992
Phase 1 Dose Escalation - Cohort 3
OBI-992 at dose level 4 mg/kg, Q3W
Intervention: OBI-992
Phase 1 Dose Escalation - Cohort 4
OBI-992 at dose level 6 mg/kg, Q3W
Intervention: OBI-992
Phase 1 Dose Escalation - Cohort 5
OBI-992 at dose level 8 mg/kg, Q3W
Intervention: OBI-992
Phase 1 Dose Escalation - Cohort 6
OBI-992 at dose level 10 mg/kg, Q3W
Intervention: OBI-992
Phase 2 Cohort Expansion - Cohort 1a
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.
Intervention: OBI-992
Phase 2 Cohort Expansion - Cohort 1b
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.
Intervention: OBI-992
Phase 2 Cohort Expansion - Cohort 2
Small cell lung cancer indication cohort - OBI-992 dosed at putative recommended phase 2 dose.
Intervention: OBI-992
Phase 2 Cohort Expansion - Cohort 3
Gastric cancer indication cohort - OBI-992 dosed at putative recommended phase 2 dose.
Intervention: OBI-992
Outcomes
Primary Outcomes
Preliminary clinical activity profile - disease control rate (DCR)
Time Frame: Duration of study, up to 2 years and 2 months
Percentage of subjects in the as-treated population with disease control according to response evaluation criteria in solid tumors (RECIST v.1.1)
Maximum tolerated dose and recommended Phase 2 dose of OBI-992
Time Frame: Duration of study, up to 2 years and 2 months
To determine the maximum tolerated dose (MTD) and optimal recommended phase 2 dose (RP2D) of OBI-992
Preliminary clinical activity profile - duration of response (DOR)
Time Frame: Duration of study, up to 2 years and 2 months
Percentage of subjects in the as-treated population with response according to response evaluation criteria in solid tumors (RECIST v.1.1)
Preliminary clinical activity profile - progression-free survival
Time Frame: Duration of study, up to 2 years and 2 months
Percentage of subjects in the as-treated population with progression-free survival according to response evaluation criteria in solid tumors (RECIST v.1.1)
Preliminary clinical activity profile - objective response rate (ORR)
Time Frame: Duration of study, up to 2 years and 2 months
Percentage of subjects in the as-treated population with objective response according to response evaluation criteria in solid tumors (RECIST v.1.1)
Safety and tolerability of OBI-992: incidence of adverse events, serious adverse events, and laboratory abnormalities
Time Frame: Duration of study, up to 2 years and 2 months
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
Preliminary clinical activity profile - clinical benefit rate (CBR)
Time Frame: Duration of study, up to 2 years and 2 months
Percentage of subjects in the as-treated population with clinical benefit according to response evaluation criteria in solid tumors (RECIST v.1.1)
Secondary Outcomes
- Serum pharmacokinetics (PK): clearance (CL) 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): Peak Plasma Concentration (Cmax) of OBI-992 and its active metabolite(Duration of study, up to 2 years and 2 months)
- Serum pharmacokinetics (PK): Volume distribution at steady state (Vdss) 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)
- Immunogenicity of OBI-992: anti-drug antibodies (ADAs)(Duration of study, up to 2 years and 2 months)