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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04045028
• Other study ID #: GO41036
• Secondary ID: 2021-006032-92
• Status: Terminated
• Phase: Phase 1
• Start date: July 22, 2019
• Est. completion date: March 28, 2023

Study information

• Verified date: April 2023
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: March 28, 2023
• Est. primary completion date: March 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Non-Hodgkin Lymphoma

Intervention

Drug:
• Tiragolumab
Administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle (Q3W)
• 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
• 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).
• Atezolizumab
Administered by IV infusion at a fixed dose of 1200 mg Q3W

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center; Internal Dept / Gastorenterology	Seoul
Korea, Republic of	Samsung Medical Center; Nephrology Department	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St.Mary's Hospital; Medical Oncology	Seoul
Korea, Republic of	Yonsei Cancer Center; Yonsei Uni Coll. Med.	Seoul
United States	Emory Clinic	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center	Denver	Colorado
United States	Virginia Cancer Specialists (Fairfax) - USOR	Fairfax	Virginia
United States	SCRI	Nashville	Tennessee
United States	University of Pennsylvania; School of Medicine	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Clinical Research Alliance	Westbury	New York

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events	Determined according to the NCI CTCAE Version 5.0	Through study completion, an average of 1 year
Secondary	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)
Secondary	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)
Secondary	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	Through study completion, an average of 1 year
Secondary	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	Through study completion, an average of 1 year
Secondary	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)
Secondary	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)