Clinical Trials /

Phase 1/2 Study of OBI-999 in Patients With Advanced Solid Tumors

NCT04084366

Description:

The purpose of this study is to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of OBI-999 as monotherapy, and to characterize the safety and preliminary clinical activity profile of the RP2D of OBI-999 in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2 Study of OBI-999 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1/2, Open-Label, Dose-Escalation and Cohort-Expansion Study Evaluating the Safety, Pharmacokinetics, and Therapeutic Activity of OBI-999 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: OBI-999-001
  • NCT ID: NCT04084366

Conditions

  • Locally Advanced Solid Tumor

Interventions

DrugSynonymsArms
OBI-999OBI-999 Escalation phase
OBI-999OBI-999 Expansion Phase

Purpose

The purpose of this study is to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of OBI-999 as monotherapy, and to characterize the safety and preliminary clinical activity profile of the RP2D of OBI-999 in patients with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
OBI-999 Escalation phaseExperimentalPart A: Five cohorts at escalating dose levels 0.4, 0.8, 1.2, 1.6 and 2.0 mg/kg (capping calculations at a maximum at 100 kg) of OBI-999 liquid form via IV infusion to establish maximum tolerated dose (MTD) and Recommended phase 2 dose (RP2D).
  • OBI-999
OBI-999 Expansion PhaseExperimentalPart B: Five cohorts of patients at RP2D of OBI-999 liquid form, as determined from Part A, via IV infusion.
  • OBI-999

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female patients, 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 patients with advanced solid tumors.

          4. Patients 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 informed consent must state the effective therapies the patient 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:

             a. Hepatic:

             i. Serum ALT ≤3 × upper limit of normal (ULN), ≤5 × ULN in the presence of liver
             metastases

             ii. Serum 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. Patient is willing and able to comply with all protocol required assessments, visits,
             and procedures, including a 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.

             Patient not of childbearing potential (i.e., permanently sterilized, postmenopausal)
             can be included in study. Postmenopausal is defined as 12 months with no menses
             without an alternative medical cause.

             Male patients 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. Patients with human immunodeficiency virus (HIV) infection are eligible if CD4+ T cell
             counts ≥ 350 cells/uL; patients on antiretroviral therapy (ART) should be on an
             established dose for at least 4 weeks and have an HIV viral load less than 400
             copies/mL prior to enrollment.

         12. Patients 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. Patients with a history of hepatitis C virus (HCV) infection should have completed
             curative antiviral treatment and have a viral load below the limit of quantification.

         14. Patients in Part B (Cohort-Expansion) must have documented Globo H H score of at least
             100 from a qualified laboratory IHC assay in one of the sponsor-selected tumor types
             to be enrolled in the respective cohort:

        Exclusion Criteria:

          1. Less than 3 weeks from prior cytotoxic chemotherapy or radiation therapy; and less
             than 5 half-lives or 6 weeks, whichever is shorter, from prior biologic therapies,
             prior to the first dose of OBI 999.

          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 999.

          3. Sensory or motor neuropathy of Grade 1 or greater.

          4. Patients 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 NCI CTCAE version 5.0), except for alopecia and laboratory values
             listed in the inclusion criteria.

          6. Receipt of any prior therapy targeting Globo H.

          7. Known hypersensitivity to OBI 999 or its excipients.

          8. Has known untreated central nervous system metastases. Patients 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 a significant clinical cardiac abnormality (e.g., clinical heart failure, unstable
             angina, or ejection fraction < 35%)

         10. Any medical co morbidity that is life threatening or, in the opinion of the
             Investigator, renders the patient unsuitable for participation in a clinical trial due
             to possible noncompliance, would place the patient at an unacceptable risk and/or
             potential to affect interpretation of results of the study.

         11. Is receiving any concurrent prohibited medication
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Measurement of dose-limiting toxicities (DLTs)
Time Frame:First 21 days of each dose escalation cohort
Safety Issue:
Description:Percentage of patients with dose-limiting toxicities (DLTs) observed

Secondary Outcome Measures

Measure:Measurement of preliminary clinical activity profile (objective response rate [ORR]) of OBI-999 in patients.
Time Frame:Week 1 to Week 106
Safety Issue:
Description:Percentage of patients with ORR per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Measure:Measurement of preliminary clinical activity profile (clinical benefit rate [CBR]) of OBI-999 in patients.
Time Frame:Week 1 to Week 106
Safety Issue:
Description:Percentage of patients with CBR per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Measure:Measurement of preliminary clinical activity profile (duration of response (DOR)]) of OBI-999 in patients.
Time Frame:Week 1 to Week 106
Safety Issue:
Description:Percentage of patients with duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Measure:Measurement of preliminary clinical activity profile (progression-free survival [PFS]) of OBI-999 in patients.
Time Frame:Week 1 to Week 106
Safety Issue:
Description:Percentage of patients with PFS per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Measure:Measurement of OBI-999 immunogenicity (anti-drug antibodies ([ADAs]) in patients
Time Frame:Week 1 to Week 106
Safety Issue:
Description:Percentage of patients with anti-OBI-999 antibodies in blood.
Measure:Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - Cmax
Time Frame:Week 1 to Week 106
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2
Measure:Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - total exposure (area under curve, [AUC])
Time Frame:Week 1 to Week 106
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2
Measure:Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - elimination half-life (t1/2)
Time Frame:Week 1 to Week 106
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2
Measure:Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - clearance (C1)
Time Frame:Week 1 to Week 106
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2
Measure:Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - time to reach maximum concentration (Tmax)
Time Frame:Week 1 to Week 106
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2
Measure:Pharmacokinetics (PK) of OBI-999 and its active metabolite (MMAE) - volume of distribution (Vd)
Time Frame:Week 1 to Week 106
Safety Issue:
Description:PK parameters will be calculated using a non-compartmental method from the PK samples collected during Cycles 1 and 2

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:OBI Pharma, Inc

Trial Keywords

  • antibody drug conjugate (ADC)

Last Updated

September 9, 2019