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

Genentech

Status and phase: Terminated; Phase 1

Conditions: Multiple Myeloma; B-Cell Lymphoma; Non-Hodgkin Lymphoma

Treatments: Drug: Rituximab; Drug: Tiragolumab; Drug: Atezolizumab; Drug: Daratumumab/rHuPH20

Study type: Interventional

Funder types: Industry

Identifiers

NCT04045028

GO41036

2021-006032-92 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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41 participants in 5 patient groups

Arm A: Tiragolumab R/R MM

Experimental group

Description:

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).

Treatment:

Drug: Tiragolumab

Arm B: Tiragolumab R/R NHL

Experimental group

Description:

Participants with relapsed or refractory (R/R) non-Hodgkin Lymphoma (NHL) will receive a single dose of 600 mg tiragolumab by IV infusion Q3W.

Treatment:

Drug: Tiragolumab

Arm C: Tiragolumab + Daratumumab R/R MM

Experimental group

Description:

Participants with R/R MM will receive 600 mg tiragolumab Q3W + daratumumab by subcutaneous (SC) injection.

Treatment:

Drug: Daratumumab/rHuPH20

Drug: Tiragolumab

Arm D: Tiragolumab + Rituximab R/R NHL

Experimental group

Description:

Participants with R/R NHL will receive 600 mg tiragolumab Q3W + rituximab by IV infusion and SC injection (optional).

Treatment:

Drug: Rituximab

Drug: Tiragolumab

Arm E: Tiragolumab + Atezolizumab + Daratumumab R/R MM

Experimental group

Description:

Participants with R/R MM will receive 600 mg tiragolumab Q3W + atezolizumab by IV infusion Q3W + daratumumab by SC injection.

Treatment:

Drug: Daratumumab/rHuPH20

Drug: Atezolizumab

Drug: Tiragolumab