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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

Primary Purpose

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

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Tiragolumab
Daratumumab/rHuPH20
Rituximab
Atezolizumab
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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, C and E (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
  • Arms C and E 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, whether investigational or approved, including chemotherapy, monoclonal antibody, radioimmunoconjugate, antibody-drug conjugate, hormonal therapy, and/or radiotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to initiation of study treatment
  • Prior treatment with any anti-TIGIT agent
  • Prior treatment with chimeric antigen receptor-T (CAR-T) therapy within 12 weeks 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 (including SARS-CoV-2), 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, C and E (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

Sites / Locations

  • Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
  • Emory Clinic
  • University of Maryland
  • Washington University
  • Clinical Research Alliance
  • Oncology Hematology Care, Inc.
  • University of Pennsylvania; School of Medicine
  • SCRI
  • Virginia Cancer Specialists (Fairfax) - USOR
  • Samsung Medical Center; Nephrology Department
  • Seoul National University Hospital
  • Yonsei Cancer Center; Yonsei Uni Coll. Med.
  • Seoul St.Mary's Hospital; Medical Oncology
  • Asan Medical Center; Internal Dept / Gastorenterology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm A: Tiragolumab R/R MM

Arm B: Tiragolumab R/R NHL

Arm C: Tiragolumab + Daratumumab R/R MM

Arm D: Tiragolumab + Rituximab R/R NHL

Arm E: Tiragolumab + Atezolizumab + Daratumumab R/R MM

Arm Description

Participants 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).

Participants with relapsed or refractory (R/R) non-Hodgkin Lymphoma (NHL) will receive a single dose of 600 mg tiragolumab by IV infusion Q3W.

Participants with R/R MM will receive 600 mg tiragolumab Q3W + daratumumab by subcutaneous (SC) injection.

Participants with R/R NHL will receive 600 mg tiragolumab Q3W + rituximab by IV infusion and SC injection (optional).

Participants with R/R MM will receive 600 mg tiragolumab Q3W + atezolizumab by IV infusion Q3W + daratumumab by SC injection.

Outcomes

Primary Outcome Measures

Percentage of Participants With Adverse Events
Determined according to the NCI CTCAE Version 5.0

Secondary Outcome Measures

Serum Concentration of Tiragolumab
Serum Concentration of Atezolizumab
Objective Response Rate (ORR) for R/R MM
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
ORR for R/R NHL
Proportion of participants with a CR or PR on two consecutive occasions >/= 4 weeks apart, according to the Lugano classification
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
Percentage of Participants With ADAs to Atezolizumab

Full Information

First Posted
July 22, 2019
Last Updated
April 6, 2023
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04045028
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 Atezolizumab and/or 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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Terminated
Why Stopped
Slow recruitment
Study Start Date
July 22, 2019 (Actual)
Primary Completion Date
March 28, 2023 (Actual)
Study Completion Date
March 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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 atezolizumab and/or 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 atezolizumab and/or daratumumab in participants with R/R MM or with rituximab in participants with R/R NHL.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Non-Hodgkin Lymphoma, B-Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Tiragolumab R/R MM
Arm Type
Experimental
Arm Description
Participants 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).
Arm Title
Arm B: Tiragolumab R/R NHL
Arm Type
Experimental
Arm Description
Participants with relapsed or refractory (R/R) non-Hodgkin Lymphoma (NHL) will receive a single dose of 600 mg tiragolumab by IV infusion Q3W.
Arm Title
Arm C: Tiragolumab + Daratumumab R/R MM
Arm Type
Experimental
Arm Description
Participants with R/R MM will receive 600 mg tiragolumab Q3W + daratumumab by subcutaneous (SC) injection.
Arm Title
Arm D: Tiragolumab + Rituximab R/R NHL
Arm Type
Experimental
Arm Description
Participants with R/R NHL will receive 600 mg tiragolumab Q3W + rituximab by IV infusion and SC injection (optional).
Arm Title
Arm E: Tiragolumab + Atezolizumab + Daratumumab R/R MM
Arm Type
Experimental
Arm Description
Participants with R/R MM will receive 600 mg tiragolumab Q3W + atezolizumab by IV infusion Q3W + daratumumab by SC injection.
Intervention Type
Drug
Intervention Name(s)
Tiragolumab
Intervention Description
Administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle (Q3W)
Intervention Type
Drug
Intervention Name(s)
Daratumumab/rHuPH20
Intervention Description
Administered by SC injection 1800 mg/30,000 U rHuPH20 weekly for a total of 6 doses, then every 3 weeks for a total of 16 doses (first dose given at Week 7), then every 4 weeks from Week 55 onward until disease progression
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Administered for a total of 8 doses. Rituximab will be administered by IV infusion for the first dose at a dose of 375 mg/m^2. After administration of at least one full infusion of IV rituximab, the SC formulation of rituximab (rituximab and rHuPH20) may be used for the remaining doses per institutional guidelines. SC rituximab will be administered at a dose of 1400 mg rituximab/23400 U rHuPH20 once weekly (QW).
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
Administered by IV infusion at a fixed dose of 1200 mg Q3W
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events
Description
Determined according to the NCI CTCAE Version 5.0
Time Frame
Through study completion, an average of 1 year
Secondary Outcome Measure Information:
Title
Serum Concentration of Tiragolumab
Time Frame
Cycles 1, 2, 3, 4, 8, 12, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years)
Title
Serum Concentration of Atezolizumab
Time Frame
Cycles 1, 2, 3, 4, 8, 12, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years)
Title
Objective Response Rate (ORR) for R/R MM
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
Time Frame
Through study completion, an average of 1 year
Title
ORR for R/R NHL
Description
Proportion of participants with a CR or PR on two consecutive occasions >/= 4 weeks apart, according to the Lugano classification
Time Frame
Through study completion, an average of 1 year
Title
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
Time Frame
Cycles 1, 2, 4, 8, 12, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years)
Title
Percentage of Participants With ADAs to Atezolizumab
Time Frame
Cycles 1, 2, 4, 8, 12, 16, 17 and then every 8 cycles (each cycle is 21 days) and at Treatment Discontinuation Visit (up to 2 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, C and E (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 Arms C and E 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, whether investigational or approved, including chemotherapy, monoclonal antibody, radioimmunoconjugate, antibody-drug conjugate, hormonal therapy, and/or radiotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to initiation of study treatment Prior treatment with any anti-TIGIT agent Prior treatment with chimeric antigen receptor-T (CAR-T) therapy within 12 weeks 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 (including SARS-CoV-2), 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, C and E (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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Emory Clinic
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63128
Country
United States
Facility Name
Clinical Research Alliance
City
Westbury
State/Province
New York
ZIP/Postal Code
11590
Country
United States
Facility Name
Oncology Hematology Care, Inc.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45236
Country
United States
Facility Name
University of Pennsylvania; School of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
SCRI
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Virginia Cancer Specialists (Fairfax) - USOR
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Samsung Medical Center; Nephrology Department
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Yonsei Cancer Center; Yonsei Uni Coll. Med.
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Seoul St.Mary's Hospital; Medical Oncology
City
Seoul
ZIP/Postal Code
137-807
Country
Korea, Republic of
Facility Name
Asan Medical Center; Internal Dept / Gastorenterology
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Learn more about this trial

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

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