Clinical Trials /

A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors.

NCT04158583

Description:

This study will evaluate the safety and tolerability of RO7296682 in participants with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors.
  • Official Title: An Open-label, Multicenter Phase 1 Study to Evaluate Safety, Tolerability, PK (Pharmacokinetics)/PD (Pharmacodynamics) of RO7296682, a T-regulatory Cell Depleting Antibody in Participants With Advanced and/or Metastatic Solid Tumors.

Clinical Trial IDs

  • ORG STUDY ID: WP41188
  • SECONDARY ID: 2019-002830-35
  • NCT ID: NCT04158583

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
RO7296682Part A

Purpose

This study will evaluate the safety and tolerability of RO7296682 in participants with advanced solid tumors.

Detailed Description

      A Phase 1, open-label, dose-escalation study designed to evaluate the safety and tolerability
      of RO7296682 in participants with advanced and/or metastatic solid tumors. RO7296682 will be
      administered by intravenous (IV) infusion every 3 weeks. This entry-into-human study is
      divided into a dose-escalation stage (Part A) and a dose expansion stage (Part B).
    

Trial Arms

NameTypeDescriptionInterventions
Part AExperimentalDose-Escalation: Mixed solid tumors participants will receive ascending doses of RO7296682. RO7296682 will be administered by intravenous (IV) infusion in a three-weekly schedule (Q3W) until either the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is defined.
  • RO7296682
Part BExperimentalDose-Expansion: Will start once MTD/RP2D dose is defined in Part A. Participants will receive a fixed dose of RO7296682 at the dosing regimen established in part A (Q3W schedule).
  • RO7296682

Eligibility Criteria

        Inclusion Criteria:

          1. Diagnosis of advanced and/or metastatic solid tumors who have progressed on a standard
             therapy, are intolerant to and/or refusing Standard-Of-Care (SOC), and/or are
             non-amenable to SOC. Participants whose tumors have known sensitizing mutation must
             have experienced disease progression (during or after treatment) or intolerance to
             treatment with a respective targeted therapy. Participants with sensitizing mutation
             but refusing respective inhibitor(s) will be eligible.

          2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

          3. Able to provide the most recent archival tumor tissue samples
             (formalin-fixed-paraffin-embedded [FFPE] blocks preferred; if not available, slides
             accepted).

          4. Adequate cardiovascular, haematological, liver and renal function.

          5. Participants on therapeutic anticoagulation must be on a stable anticoagulant regimen.

        Exclusion Criteria:

          1. Pregnancy, lactation, or breastfeeding.

          2. Known hypersensitivity to any of the components of RO7296682, including but not
             limited to hypersensitivity to Chinese hamster ovary cell products or other
             recombinant human or humanized antibodies.

          3. History or clinical evidence of central nervous system (CNS) primary tumors or
             metastases.

          4. Participants with another invasive malignancy in the last two years.

          5. Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results.

          6. Participants with known active or uncontrolled infection.

          7. Positive HIV test at screening.

          8. Positive for Hepatitis B and C.

          9. Vaccination with live vaccines within 28 days prior to C1D1.

         10. Major surgical procedure or significant traumatic injury within 28 days prior to first
             RO7296682 infusion.

         11. Participants with wound healing complications.

         12. Dementia or altered mental status that would prohibit informed consent.

         13. History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (drug rash
             with eosinophilia and systemic symptoms).

         14. Active or history of autoimmune disease or immune deficiency.

         15. Prior treatment with CPIs (e.g. anti-CTLA4, anti-PD1, anti-PDL1), immunomodulatory
             monoclonal antibodies (mAbs) and/or mAb-derived therapies (approved or
             investigational).

         16. Prior treatment with a CC chemokine receptor 4 (CCR4)-targeting (e.g. mogamulizumab)
             or a CD25-targeting agent (e.g. basiliximab) is prohibited.

         17. Concurrent therapy with any other investigational drug (defined as treatment for which
             there is currently no regulatory authority-approved indication) within 28 days or 5
             half-lives of the drug (whichever is shorter), prior to the first RO7296882
             administration on C1D1.

         18. Radiotherapy within the last 4 weeks before start of study drug treatment, with the
             exception of limited palliative radiotherapy (for which no wash out period is
             required).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events
Time Frame:Up to 28 months
Safety Issue:
Description:Severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0)

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Area under the curve (AUC) of RO7296682
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Minimum Concentration (Cmin) of RO7296682
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Maximum Concentration (Cmax) of RO7296682
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Clearance (CL) of RO7296682
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Volume of distribution at steady-state conditions (Vss) of RO7296682
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Half-life (t~1/2) of RO7296682
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Time of maximum concentration (Tmax) of RO7296682
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Incidence and titer of Anti-Drug Antibodies (ADA) during the study relative to the prevalence of ADA at baseline
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Treatment-induced changes in Treg levels in blood and/or tumor as compared to baseline
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Treatment-induced changes in Treg/Teff (T-regulatory cell; T-effector cell) ratio in blood and/or tumor as compared to baseline
Time Frame:Up to 28 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

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