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

Sponsor
Genentech, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04045028
Collaborator
(none)
60
Enrollment
12
Locations
5
Arms
52.3
Anticipated Duration (Months)
5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 22, 2019
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm A: Tiragolumab R/R MM

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).

Drug: Tiragolumab
Administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle (Q3W)

Experimental: Arm B: Tiragolumab R/R NHL

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

Drug: Tiragolumab
Administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle (Q3W)

Experimental: Arm C: Tiragolumab + Daratumumab R/R MM

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

Drug: Tiragolumab
Administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle (Q3W)

Drug: Daratumumab/rHuPH20
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

Experimental: Arm D: Tiragolumab + Rituximab R/R NHL

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

Drug: Tiragolumab
Administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle (Q3W)

Drug: Rituximab
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).

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

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

Drug: Tiragolumab
Administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle (Q3W)

Drug: Daratumumab/rHuPH20
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

Drug: Atezolizumab
Administered by IV infusion at a fixed dose of 1200 mg Q3W

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With Adverse Events [Through study completion, an average of 1 year]

    Determined according to the NCI CTCAE Version 5.0

Secondary Outcome Measures

  1. Serum Concentration of Tiragolumab [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)]

  2. Serum Concentration of Atezolizumab [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)]

  3. Objective Response Rate (ORR) for R/R MM [Through study completion, an average of 1 year]

    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

  4. ORR for R/R NHL [Through study completion, an average of 1 year]

    Proportion of participants with a CR or PR on two consecutive occasions >/= 4 weeks apart, according to the Lugano classification

  5. Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab [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)]

  6. Percentage of Participants With ADAs to Atezolizumab [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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical CenterDenverColoradoUnited States80218
2Emory ClinicAtlantaGeorgiaUnited States30322
3University of MarylandBaltimoreMarylandUnited States21201
4Washington UniversitySaint LouisMissouriUnited States63128
5Oncology Hematology Care, Inc.; Oncology Hematology Care, Inc.CincinnatiOhioUnited States45236
6University of Pennsylvania; School of MedicinePhiladelphiaPennsylvaniaUnited States19104
7SCRINashvilleTennesseeUnited States37203
8Virginia Cancer Specialists (Fairfax) - USORFairfaxVirginiaUnited States22031
9Samsung Medical Center; Nephrology DepartmentSeoulKorea, Republic of06351
10Seoul National University Hospital; Seoul National University HospitalSeoulKorea, Republic of110-744
11Seoul St.Mary's Hospital; Medical OncologySeoulKorea, Republic of137-807
12Asan Medical Center; Internal Dept / GastorenterologySeoulKorea, Republic of138-736

Sponsors and Collaborators

  • Genentech, Inc.

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT04045028
Other Study ID Numbers:
  • GO41036
First Posted:
Aug 5, 2019
Last Update Posted:
Dec 28, 2021
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 28, 2021