Safety and Pharmacokinetics (PK) of Escalating Doses of Tiragolumab as a Single Agent and in Combination With Atezolizumab and/or Other Anti-Cancer Therapies in Locally Advanced or Metastatic Tumors

Genentech

Status and phase: Completed; Phase 1

Conditions: Advanced/Metastatic Tumors

Treatments: Drug: Capecitabine; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Etoposide; Drug: Tiragolumab; Drug: Cisplatin; Drug: Pembrolizumab; Drug: Atezolizumab; Drug: Bevacizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02794571

2016-000944-33 (EudraCT Number)

GO30103

Details and patient eligibility

About

This first-in-human open-label, multicenter, dose-escalation and expansion study is designed to evaluate the safety, tolerability, and PK of tiragolumab alone or in combination with atezolizumab and/or other anti-cancer therapies in participants with locally advanced, recurrent, or metastatic incurable tumors for whom standard therapy does not exist, has proven to be ineffective or intolerable, or is considered inappropriate, or for whom a clinical trial of an investigational agent is a recognized standard of care.

Enrollment: 518 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults 18 years of age or older
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy at least 12 weeks
• Adequate hematologic and end organ function
• Histologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for which standard therapy has proven ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care
• Confirmed availability of representative tumor specimens
• Measurable disease according to RECIST Version 1.1

Exclusion criteria

• Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment
• Malignancies other than disease under study within 5 years prior to Day 1 of Cycle 1
• Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases
• Leptomeningeal disease
• History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on Screening chest computed tomograph (CT) scan
• History of autoimmune disease
• Positive human immunodeficiency virus (HIV) test
• Active hepatitis B or C, or tuberculosis
• Severe infection within 4 weeks prior to randomization
• Prior allogeneic bone marrow or solid organ transplant
• Significant cardiovascular disease
• Known clinically significant liver disease

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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518 participants in 12 patient groups

Phase Ia Dose-Escalation Stage: Tiragolumab

Experimental group

Description:

Cohorts of at least 3 participants each will be treated with escalating doses of tiragolumab.

Treatment:

Drug: Tiragolumab

Phase Ia Dose-Expansion Stage: Tiragolumab

Experimental group

Description:

Participants will be treated with tiragolumab at or below the maximum tolerated dose (MTD) or maximum administered dose (MAD) in the study.

Treatment:

Drug: Tiragolumab

Phase Ib Q3W Dose-Escalation Stage: Tiragolumab+Atezolizumab

Experimental group

Description:

A minimum of 3 participants will be treated for each dose level of tiragolumab in combination with a fixed dose of atezolizumab with tiragolumab being administered prior to atezolizumab.

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

Phase Ib Q3W Dose-Expansion Stage: Tiragolumab+Atezolizumab

Experimental group

Description:

Participants will be treated every 3 weeks (Q3W) with tiragolumab at or below the MTD or MAD in combination with a fixed dose of atezolizumab with tiragolumab being administered prior to atezolizumab.

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A

Experimental group

Description:

In Cohort A, carboplatin or cisplatin and pemetrexed chemotherapy will be administered after atezolizumab and tiragolumab intravenous (IV) infusion. During induction phase, participants will receive atezolizumab and tiragolumab in combination with carboplatin or cisplatin and pemetrexed on Day 1 of each 21-day cycle for 4 to 6 cycles. During maintenance phase, participants will receive atezolizumab and tiragolumab in combination with pemetrexed on Day 1 of each 21-day cycle.

Treatment:

Drug: Atezolizumab

Drug: Cisplatin

Drug: Tiragolumab

Drug: Pemetrexed

Drug: Carboplatin

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B

Experimental group

Description:

In Cohort B, carboplatin and paclitaxel chemotherapy will be administered after atezolizumab and tiragolumab IV infusion. During induction phase, participants will receive atezolizumab and tiragolumab in combination with carboplatin and paclitaxel on Day 1 of each 21-day cycle for 4 to 6 cycles. During maintenance phase, participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle (participants enrolled under protocol version 4) or Day 1 of each 28-day cycle (participants enrolled under protocol version 5).

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

Drug: Paclitaxel

Drug: Carboplatin

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C

Experimental group

Description:

In Cohort C, carboplatin or cisplatin and etoposide chemotherapy will be administered after atezolizumab and tiragolumab IV infusion. During induction phase, participants will receive atezolizumab and tiragolumab in combination with carboplatin or cisplatin on Day 1 of each 21-day cycle and etoposide on Day 1 to 3 of each 21-day cycle for 4 cycles. During maintenance phase, participants will receive atezolizumab and tiragolumab on Day 1 of each 28-day cycle.

Treatment:

Drug: Atezolizumab

Drug: Cisplatin

Drug: Tiragolumab

Drug: Etoposide

Drug: Carboplatin

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort D

Experimental group

Description:

In Cohort D, participants will receive atezolizumab and tiragolumab on Day 1 and capecitabine on Day 1-14 of each 21-day cycle.

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

Drug: Capecitabine

Phase Ib Q4W Sequential Dose-Expansion Stage: Tiragolumab+Atezolizumab

Experimental group

Description:

Participants will be treated every 4 weeks (Q4W) with fixed doses of tiragolumab and atezolizumab with tiragolumab being administered prior to atezolizumab.

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

Phase Ib Q4W Coinfusion Expansion Cohort Tiragolumab+Atezolizumab

Experimental group

Description:

Participants will be treated Q4W with fixed doses of tiragolumab and atezolizumab mixed and administered in one IV bag.

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC1

Experimental group

Description:

In Cohort NC1, participants will receive atezolizumab and tiragolumab in combination with bevacizumab on Day 1 of each 21-day cycle.

Treatment:

Drug: Bevacizumab

Drug: Atezolizumab

Drug: Tiragolumab

Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC2

Experimental group

Description:

In Cohort NC2, participants will receive tiragolumab in combination with pembrolizumab on Day 1 of each 21-day cycle.

Treatment:

Drug: Pembrolizumab

Drug: Tiragolumab