Clinical Trials /

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD), and Preliminary Activity of Tiragolumab in Participants With Relapsed or Refractory Multiple Myeloma or With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT04045028

Description:

This is a Phase I open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity of tiragolumab administered as a single agent or in combination with daratumumab or rituximab in participants with relapsed or refractory (R/R) multiple myeloma (MM) or R/R non-Hodgkin lymphoma (NHL).

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), Pharmacodynamics (PD), and Preliminary Activity of Tiragolumab in Participants With Relapsed or Refractory Multiple Myeloma or With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
  • Official Title: A Phase Ia/Ib Open-Label, Multicenter Study Evaluating The Safety and Pharmacokinetics of Tiragolumab as a Single Agent and In Combination With Daratumumab In Patients With Relapsed Or Refractory Multiple Myeloma, and As a Single Agent and In Combination With Rituximab In Patients With Relapsed Or Refractory B-Cell Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: GO41036
  • NCT ID: NCT04045028

Conditions

  • Multiple Myeloma
  • Non-Hodgkin Lymphoma
  • B-Cell Lymphoma

Interventions

DrugSynonymsArms
TiragolumabArm A (Phase Ia)
DaratumumabArm C (Phase Ib)
RituximabArm D (Phase Ib)

Purpose

This is a Phase I open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity of tiragolumab administered as a single agent or in combination with daratumumab or rituximab in participants with relapsed or refractory (R/R) multiple myeloma (MM) or R/R non-Hodgkin lymphoma (NHL).

Detailed Description

      In the Phase Ia part of the study, tiragolumab is administered as a single agent in
      participants with R/R MM or R/R NHL.

      In the Phase Ib part of the study, tiragolumab is administered in combination with
      daratumumab in participants with R/R MM or with rituximab in participants with R/R NHL for
      whom combination therapy is considered an acceptable treatment option.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (Phase Ia)ExperimentalParticipants with relapsed or refractory (R/R) Multiple Myeloma (MM) will receive a single dose of 600 mg Tiragolumab by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W)
  • Tiragolumab
Arm B (Phase Ia)ExperimentalParticipants with relapsed or refractory (R/R) non-Hodgkin Lymphoma (NHL) will receive a single dose of 600 mg Tiragolumab by IV infusion Q3W
  • Tiragolumab
Arm C (Phase Ib)ExperimentalParticipants with R/R MM will receive 600 mg Tiragolumab Q3W + Daratumumab by IV infusion
  • Tiragolumab
  • Daratumumab
Arm D (Phase Ib)ExperimentalParticipants with R/R NHL will receive 600 mg Tiragolumab Q3W + Rituximab by IV infusion
  • Tiragolumab
  • Rituximab

Eligibility Criteria

        Inclusion Criteria:

        General Inclusion Criteria (All Participants):

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

          -  Life expectancy of >/= 12 weeks

        Inclusion Criteria Specific to Arms A and C (R/R MM)

          -  Arm A only: Must have R/R MM for which no established therapy for MM is appropriate
             and available or be intolerant to those established therapies

          -  Arm C only: Participants with R/R MM who have received at least 3 prior lines of
             therapy.

          -  Measurable disease defined by laboratory test results.

        Inclusion Criteria Specific to Arms B and D (R/R NHL)

          -  Participants with histologically confirmed B-cell NHL who have relapsed or failed to
             respond to at least two prior systemic treatment regimens and for which no suitable
             therapy of curative intent or higher priority exists.

          -  Must have at least one bi-dimensionally measurable lesion.

        Exclusion Criteria:

        General Exclusion Criteria (All Participants)

          -  Any anti-cancer therapy including chemotherapy, monoclonal antibody,
             radioimmunoconjugate, antibody-drug conjugate, hormonal therapy, and/or radiotherapy,
             within 4 weeks prior to initiation of study treatment

          -  Prior treatment with any anti-TIGIT agent

          -  Prior treatment with chimeric antigen receptor-T (CAR-T) therapy within 30 days before
             first study drug administration

          -  Autologous Stem-Cell Transplantation (ASCT) within 100 days prior to first study drug
             administration

          -  Active or history of autoimmune disease or immune deficiency

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at
             study enrollment, or any major episode of infection within 4 weeks prior to first
             study drug administration

        Exclusion Criteria Specific to Arms A and C (R/R MM)

          -  Primary or secondary plasma cell leukemia

          -  Current or history of CNS involvement by MM

        Exclusion Criteria Specific to Arms B and D (R/R NHL)

          -  Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of
             bisphosphonate therapy or denosumab

          -  Current or history of CNS lymphoma

          -  Current eligibility for ASCT

        Other protocol defined inclusion/exclusion criteria could apply
      
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:Through study completion, an average of 1 year
Safety Issue:
Description:Determined according to the NCI CTCAE Version 5.0

Secondary Outcome Measures

Measure:Serum Concentration of Tiragolumab
Time Frame:Cycles 1, 2, 3, 4, 8, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years)
Safety Issue:
Description:
Measure:Objective Response Rate (ORR) for R/R MM
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:Proportion of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR), as defined by the International Myeloma Working Group (IMWG) criteria
Measure:ORR for R/R NHL
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:Proportion of participants with a CR or PR on two consecutive occasions >/= 4 weeks apart, according to the Lugano classification
Measure:Percentage of Participants With Anti-Drug Antibodies (ADA) to Tiragolumab
Time Frame:Cycles 1, 2, 4, 8, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

November 19, 2019