Clinical Trials /

A Study Evaluating Safety, Pharmacokinetics, and Therapeutic Activity of RO6874281 as a Single Agent (Part A) or in Combination With Trastuzumab or Cetuximab (Part B or C)

NCT02627274

Description:

This first-in-human, open-label, multicenter, Phase Ia/Ib, adaptive, multiple ascending-dose study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of RO6874281 as a single agent (Part A) or in combination with trastuzumab or cetuximab (Part B or C).

Related Conditions:
  • Breast Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating Safety, Pharmacokinetics, and Therapeutic Activity of RO6874281 in Participants With Advanced and/or Metastatic Solid Tumors
  • Official Title: An Open-label, Multicenter, Dose-escalation, Phase I Study to Evaluate Safety, Pharmacokinetics, and Therapeutic Activity of RO6874281, an Immunocytokine Consisting of Interleukin 2 Variant (IL-2v) Targeting Fibroblast Activation Protein-Alpha (FAP), in Patients With Advanced and/or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BP29842
  • SECONDARY ID: 2015-002251-97
  • SECONDARY ID: RG7461
  • NCT ID: NCT02627274

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
RO6874281RO6874281

Purpose

This open-label, multicenter, dose-escalation study will evaluate the safety, pharmacokinetics and therapeutic activity of RO6874281 in participants with advanced and/or metastatic solid tumors. Participants will be treated until disease progression or unacceptable toxicity occurs, for up to a maximum of 24 months.

Trial Arms

NameTypeDescriptionInterventions
RO6874281ExperimentalParticipants will receive RO6874281, starting with 5 mg once weekly (QW) to a maximum of 50 mg QW, as a single administration by intravenous infusion over a minimum of 2 hours (120 minutes) with a maximum infusion rate of 25 mg/hour. Participants will receive RO6874281 until clinical disease progression, unacceptable toxicities, or withdrawal of consent. Participants may continue treatment with RO6874281 for a maximum of 24 months.
  • RO6874281

Eligibility Criteria

        Inclusion Criteria:

          -  Age greater than or equal to (>=) 18 years

          -  Confirmed advanced and/or metastatic solid tumor, with at least one tumor lesion of
             location accessible to biopsy per clinical judgment of the treating physician, and
             confirmed progression at baseline; who have progressed on a cancer therapy or for
             whom no effective standard therapy exists

          -  Radiologically measurable and clinically evaluable disease

          -  Life expectancy of >=12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0- 1

          -  Adequate cardiovascular, hematological, liver and renal function

          -  All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical
             procedure must have resolved to Grade less than or equal to (<=) 1, except alopecia
             (any grade) and Grade 2 peripheral neuropathy

          -  Negative serum pregnancy test within 7 days prior to study treatment in premenopausal
             women and women less than (<) 12 months after menopause

          -  For women who are not postmenopausal and have not undergone surgical sterilization:
             agreement to remain abstinent or use two adequate non hormonal methods of
             contraception, including at least one method with a failure rate of <1 percent (%)
             per year, during the treatment period and for at least 4 months after the last dose
             of study drug

          -  For men: agreement to remain abstinent or use contraceptive measures and agreement to
             refrain from donating sperm during the treatment period and for at least for at least
             2 months after the last dose of study drug

          -  Participants with Gilbert's syndrome will be eligible for the study

        Exclusion Criteria:

          -  History or clinical evidence of Central Nervous System (CNS) primary tumors or
             metastases including leptomeningeal metastases, unless they have been previously
             treated, are asymptomatic, and have had no requirement for steroids or enzyme
             inducing anticonvulsants in the last 14 days prior to screening

          -  Participants with an active second malignancy

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results, including diabetes
             mellitus, history of relevant pulmonary disorders, and known autoimmune diseases or
             other disease with ongoing fibrosis

          -  Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of
             study drug administration

          -  Active or uncontrolled infections

          -  Known human immunodeficiency virus (HIV) or known active hepatitis B virus or
             hepatitis C virus infection

          -  History of chronic liver disease or evidence of hepatic cirrhosis

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding that give reasonable suspicion of a disease or condition that
             would contraindicate the use of an investigational drug

          -  Major surgery or significant traumatic injury <28 days prior to the first RO6874281
             infusion (excluding biopsies) or anticipation of the need for major surgery during
             study treatment

          -  Dementia or altered mental status that would prohibit informed consent

          -  Pregnant or breastfeeding women

          -  Known hypersensitivity to any of the components of RO6874281

          -  Concurrent therapy with any other investigational drug

          -  Immunomodulating agents <28 days prior to first dose of study drug
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Dose-limiting Toxicities (DLT)
Time Frame:up to Day 21
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Blood Levels of Cluster of Differentiation (CD)4+ T Cells
Time Frame:C1D1, C1D2, C1D3, and C1D5; C2D1, C2D2, and C2D3; C3D1, C3D2, C3D3, and C3D5; C4D1, C4D2, C4D3; C5D1, C5D2, C5D3, and C5D5; and at D1, D2 for subsequent cycles, and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of CD8+ T Cells
Time Frame:C1D1, C1D2, C1D3, and C1D5; C2D1, C2D2, and C2D3; C3D1, C3D2, C3D3, and C3D5; C4D1, C4D2, C4D3; C5D1, C5D2, C5D3, and C5D5; and at D1, D2 for subsequent cycles, and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of CD25+ T Cells
Time Frame:C1D1, C1D2, C1D3, and C1D5; C2D1, C2D2, and C2D3; C3D1, C3D2, C3D3, and C3D5; C4D1, C4D2, C4D3; C5D1, C5D2, C5D3, and C5D5; and at D1, D2 for subsequent cycles, and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Natural Killer (NK) Cells
Time Frame:C1D1, C1D2, C1D3, and C1D5; C2D1, C2D2, and C2D3; C3D1, C3D2, C3D3, and C3D5; C4D1, C4D2, C4D3; C5D1, C5D2, C5D3, and C5D5; and at D1, D2 for subsequent cycles, and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Monocytes
Time Frame:C1D1, C1D2, C1D3, and C1D5; C2D1, C2D2, and C2D3; C3D1, C3D2, C3D3, and C3D5; C4D1, C4D2, C4D3; C5D1, C5D2, C5D3, and C5D5; and at D1, D2 for subsequent cycles, and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of C-Reactive Protein
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Interferon Gamma
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Interleukin 2
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Interleukin 4
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Interleukin 6
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Interleukin 8
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Interleukin 10
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Interleukin 12p70
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Soluble CD25
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Levels of CD4+ T cells in Tumor Samples
Time Frame:Predose and Cycle 7 Day 1 (±2 days)
Safety Issue:
Description:
Measure:Levels of CD8+ T Cells in Tumor Samples
Time Frame:Predose and Cycle 7 Day 1 (±2 days)
Safety Issue:
Description:
Measure:Levels of NK Cells in Tumor Samples
Time Frame:Predose and Cycle 7 Day 1 (±2 days)
Safety Issue:
Description:
Measure:Levels of Programmed Death-Ligand 1 (PD-L1) in Tumor Samples
Time Frame:Predose and Cycle 7 Day 1 (±2 days)
Safety Issue:
Description:
Measure:Fibroblast Activation Protein-Alpha (FAP) Expression
Time Frame:Screening (Day -28 to Day -1)
Safety Issue:
Description:
Measure:Percentage of Participants With Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and Immune-Related Response Criteria (irRC)
Time Frame:Day 1 up to 24 months
Safety Issue:
Description:
Measure:Percentage of Participants With Disease Control According to RECIST v1.1 and irRC
Time Frame:Day 1 up to 24 months
Safety Issue:
Description:
Measure:Progression-free Survival (PFS) According to RECIST v1.1 and irRC
Time Frame:Day 1 up to 24 months
Safety Issue:
Description:
Measure:Overall Survival (OS) According to RECIST v1.1 and irRC
Time Frame:Day 1 up to 24 months
Safety Issue:
Description:
Measure:Blood Levels of Regulatory T (Treg) Cells
Time Frame:C1D1, C1D2, C1D3, and C1D5; C2D1, C2D2, and C2D3; C3D1, C3D2, C3D3, and C3D5; C4D1, C4D2, C4D3; C5D1, C5D2, C5D3, and C5D5; and at D1, D2 for subsequent cycles, and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of B Cells
Time Frame:C1D1, C1D2, C1D3, and C1D5; C2D1, C2D2, and C2D3; C3D1, C3D2, C3D3, and C3D5; C4D1, C4D2, C4D3; C5D1, C5D2, C5D3, and C5D5; and at D1, D2 for subsequent cycles, and at follow up visit (up to 24 months)
Safety Issue:
Description:
Measure:Blood Levels of Tumor Necrosis Factor-Alpha
Time Frame:D1, D2 of every cycles and at follow up visit (up to 24 months)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

March 13, 2017