Clinical trial NCT04045028: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Non-Hodgkin Lymphoma
B-Cell Lymphoma
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-05
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Serum Concentration of Tiragolumab
timeFrame: 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)
measure: Serum Concentration of Atezolizumab
timeFrame: 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)
measure: Objective Response Rate (ORR) for R/R MM
timeFrame: Through study completion, an average of 1 year
measure: ORR for R/R NHL
timeFrame: Through study completion, an average of 1 year
measure: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
timeFrame: 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)
measure: Percentage of Participants With ADAs to Atezolizumab
timeFrame: 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)
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
state: Colorado
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Westbury
country: United States
facility: Clinical Research Alliance
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania; School of Medicine
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI
state: Tennessee
city: Fairfax
country: United States
facility: Virginia Cancer Specialists (Fairfax) - USOR
state: Virginia
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center; Nephrology Department
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei Cancer Center; Yonsei Uni Coll. Med.
city: Seoul
country: Korea, Republic of
facility: Seoul St.Mary's Hospital; Medical Oncology
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center; Internal Dept / Gastorenterology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: