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

• ClinicalTrials.gov Identifier: NCT04045028
• Recruitment Status: Terminated
• First Posted: August 5, 2019
• Last Update Posted: April 7, 2023
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

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).

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; Non-Hodgkin Lymphoma; B-Cell Lymphoma	Drug: Tiragolumab; Drug: Daratumumab/rHuPH20; Drug: Rituximab; Drug: Atezolizumab	Phase 1

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 (Clinical Trial)
• Actual Enrollment: 41 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: July 22, 2019
• Actual Primary Completion Date: March 28, 2023
• Actual Study Completion Date: March 28, 2023

Arms and Interventions

Arm	Intervention/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 [ Time Frame: 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 [ 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) ]
2. 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) ]
3. Objective Response Rate (ORR) for R/R MM [ Time Frame: 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 [ Time Frame: 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 [ 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) ]
6. 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) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Colorado

Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center

Denver, Colorado, United States, 80218

United States, Georgia

Emory Clinic

Atlanta, Georgia, United States, 30322

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63128

United States, New York

Clinical Research Alliance

Westbury, New York, United States, 11590

United States, Ohio

Oncology Hematology Care, Inc.

Cincinnati, Ohio, United States, 45236

United States, Pennsylvania

University of Pennsylvania; School of Medicine

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

SCRI

Nashville, Tennessee, United States, 37203

United States, Virginia

Virginia Cancer Specialists (Fairfax) - USOR

Fairfax, Virginia, United States, 22031

Korea, Republic of

Samsung Medical Center; Nephrology Department

Seoul, Korea, Republic of, 06351

Seoul National University Hospital

Seoul, Korea, Republic of, 110-744

Yonsei Cancer Center; Yonsei Uni Coll. Med.

Seoul, Korea, Republic of, 120-752

Seoul St.Mary's Hospital; Medical Oncology

Seoul, Korea, Republic of, 137-807

Asan Medical Center; Internal Dept / Gastorenterology

Seoul, Korea, Republic of, 138-736

Sponsors and Collaborators

Genentech, Inc.

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT04045028
• Other Study ID Numbers: GO41036; 2021-006032-92 ( EudraCT Number )
• First Posted: August 5, 2019
• Last Update Posted: April 7, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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).

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

Additional relevant MeSH terms:

Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Rituximab; Atezolizumab; Daratumumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action