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
- Conditions
- Multiple MyelomaNon-Hodgkin LymphomaB-Cell Lymphoma
- Interventions
- Registration Number
- NCT04045028
- Lead Sponsor
- Genentech, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 41
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.
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Tiragolumab R/R MM Tiragolumab 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 B: Tiragolumab R/R NHL Tiragolumab 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 C: Tiragolumab + Daratumumab R/R MM Daratumumab/rHuPH20 Participants with R/R MM will receive 600 mg tiragolumab Q3W + daratumumab by subcutaneous (SC) injection. Arm E: Tiragolumab + Atezolizumab + Daratumumab R/R MM Daratumumab/rHuPH20 Participants with R/R MM will receive 600 mg tiragolumab Q3W + atezolizumab by IV infusion Q3W + daratumumab by SC injection. Arm C: Tiragolumab + Daratumumab R/R MM Tiragolumab Participants with R/R MM will receive 600 mg tiragolumab Q3W + daratumumab by subcutaneous (SC) injection. Arm D: Tiragolumab + Rituximab R/R NHL Tiragolumab Participants with R/R NHL will receive 600 mg tiragolumab Q3W + rituximab by IV infusion and SC injection (optional). Arm D: Tiragolumab + Rituximab R/R NHL Rituximab Participants with R/R NHL will receive 600 mg tiragolumab Q3W + rituximab by IV infusion and SC injection (optional). Arm E: Tiragolumab + Atezolizumab + Daratumumab R/R MM Atezolizumab Participants with R/R MM will receive 600 mg tiragolumab Q3W + atezolizumab by IV infusion Q3W + daratumumab by SC injection. Arm E: Tiragolumab + Atezolizumab + Daratumumab R/R MM Tiragolumab Participants with R/R MM will receive 600 mg tiragolumab Q3W + atezolizumab by IV infusion Q3W + daratumumab by SC injection.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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) 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) 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
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) 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) 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
Trial Locations
- Locations (14)
Virginia Cancer Specialists (Fairfax) - USOR
🇺🇸Fairfax, Virginia, United States
Clinical Research Alliance
🇺🇸Westbury, New York, United States
University of Pennsylvania; School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Asan Medical Center; Internal Dept / Gastorenterology
🇰🇷Seoul, Korea, Republic of
Washington University
🇺🇸Saint Louis, Missouri, United States
Samsung Medical Center; Nephrology Department
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Yonsei Cancer Center; Yonsei Uni Coll. Med.
🇰🇷Seoul, Korea, Republic of
Seoul St.Mary's Hospital; Medical Oncology
🇰🇷Seoul, Korea, Republic of
Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Emory Clinic
🇺🇸Atlanta, Georgia, United States
Oncology Hematology Care, Inc.
🇺🇸Cincinnati, Ohio, United States
SCRI
🇺🇸Nashville, Tennessee, United States