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

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

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).

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma; Non-Hodgkin Lymphoma; B-Cell Lymphoma
• Intervention / Treatment: Drug: Tiragolumab; Drug: Daratumumab/rHuPH20; Drug: Rituximab; Drug: Atezolizumab

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 Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GO41036 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 137-807
    • Seoul St.Mary's Hospital; Medical Oncology
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center; Nephrology Department
  • Seoul, Korea, Republic of, 120-752
    • Yonsei Cancer Center; Yonsei Uni Coll. Med.
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center; Internal Dept / Gastorenterology
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Washington University
  • New York
    • Westbury, New York, United States, 11590
      • Clinical Research Alliance
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care, Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania; School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists (Fairfax) - USOR

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	Determined according to the NCI CTCAE Version 5.0	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
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)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Actual): March 28, 2023
• Study Completion (Actual): March 28, 2023

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 5, 2019

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Lymphoma; Lymphoma, B-Cell; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Daratumumab; Rituximab; Atezolizumab
• Other Study ID Numbers: GO41036; 2021-006032-92 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No