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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02794571




Registration number
NCT02794571
Ethics application status
Date submitted
6/06/2016
Date registered
9/06/2016
Date last updated
22/08/2024

Titles & IDs
Public title
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
Scientific title
A Phase Ia/Ib Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Tiragolumab as a Single Agent and in Combination With Atezolizumab and/or Other Anti-Cancer Therapies in Patients With Locally Advanced or Metastatic Tumors
Secondary ID [1] 0 0
2016-000944-33
Secondary ID [2] 0 0
GO30103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced/Metastatic Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Tiragolumab
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Etoposide
Treatment: Drugs - Capecitabine
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Pembrolizumab

Experimental: Phase Ia Dose-Escalation Stage: Tiragolumab - Cohorts of at least 3 participants each will be treated with escalating doses of tiragolumab.

Experimental: Phase Ia Dose-Expansion Stage: Tiragolumab - Participants will be treated with tiragolumab at or below the maximum tolerated dose (MTD) or maximum administered dose (MAD) in the study.

Experimental: Phase Ib Q3W Dose-Escalation Stage: Tiragolumab+Atezolizumab - 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.

Experimental: Phase Ib Q3W Dose-Expansion Stage: Tiragolumab+Atezolizumab - 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.

Experimental: Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A - 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.

Experimental: Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B - 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).

Experimental: Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C - 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.

Experimental: Phase Ib Chemotherapy Dose-Expansion Stage: Cohort D - In Cohort D, participants will receive atezolizumab and tiragolumab on Day 1 and capecitabine on Day 1-14 of each 21-day cycle.

Experimental: Phase Ib Q4W Sequential Dose-Expansion Stage: Tiragolumab+Atezolizumab - Participants will be treated every 4 weeks (Q4W) with fixed doses of tiragolumab and atezolizumab with tiragolumab being administered prior to atezolizumab.

Experimental: Phase Ib Q4W Coinfusion Expansion Cohort Tiragolumab+Atezolizumab - Participants will be treated Q4W with fixed doses of tiragolumab and atezolizumab mixed and administered in one IV bag.

Experimental: Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC1 - In Cohort NC1, participants will receive atezolizumab and tiragolumab in combination with bevacizumab on Day 1 of each 21-day cycle.

Experimental: Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC2 - In Cohort NC2, participants will receive tiragolumab in combination with pembrolizumab on Day 1 of each 21-day cycle.


Treatment: Drugs: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.

Treatment: Drugs: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.

Treatment: Drugs: Carboplatin
Carboplatin, AUC of 6 milligram per milliliter per minute (mg/ml/min) for Cohorts A and B and AUC of 5 mg/ml/min for Cohort C, IV infusion will be administered on Day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab IV infusion.

Treatment: Drugs: Cisplatin
Cisplatin 75 milligram per square meter (mg/m\^2) IV infusion will be administered on day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab.

Treatment: Drugs: Pemetrexed
Pemetrexed 500 mg/m\^2 IV infusion will be administered on Day 1 of each 21-day cycle after carboplatin or cisplatin IV infusion with combination treatment of atezolizumab and tiragolumab.

Treatment: Drugs: Paclitaxel
Paclitaxel 200 mg/m\^2 IV infusion will be administered on Day 1 of each 21-day cycle after combination treatment with atezolizumab and tiragolumab.

Treatment: Drugs: Etoposide
Etoposide 100 mg/m\^2 IV infusion will be administered on Days 1, 2, and 3 of each 21-day cycle with combination treatment of atezolizumab and tiragolumab.

Treatment: Drugs: Capecitabine
Capecitabine 1250 mg/m\^2 oral dose will be administered twice daily (BID) on Days 1 through 14 of each 21-day cycle. On Day 1 of Cycle 1, the first dose of capecitabine will be administered prior to the atezolizumab and tiragolumab infusion.

Treatment: Drugs: Bevacizumab
Bevacizumab 15 mg/kg IV infusion will be administered on Day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab.

Treatment: Drugs: Pembrolizumab
Pembrolizumab 200 mg IV infusion will be administered on Day 1 of each 21-day cycle after treatment with tiragolumab.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
From Baseline to the end of Cycle 1 (up to 21 days)
Primary outcome [2] 0 0
Percentage of Participants with Adverse Events (AEs) Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
Timepoint [2] 0 0
From Baseline up to 90 days after last dose of study treatment or until initiation of another systemic anti-cancer therapy (up to approximately 8 years)
Primary outcome [3] 0 0
Number of Cycles with Tiragolumab
Timepoint [3] 0 0
From Baseline to last dose (up to approximately 8 years)
Primary outcome [4] 0 0
Phase Ia and Ib: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Tiragolumab
Timepoint [4] 0 0
Day 1 up to 8 years
Primary outcome [5] 0 0
Phase Ib: Percentage of Participants with ADAs to Atezolizumab
Timepoint [5] 0 0
Day 1 up to 8 years
Secondary outcome [1] 0 0
Area Under the Concentration-Time Curve (AUC) of Tiragolumab
Timepoint [1] 0 0
Day 1 up to 8 years
Secondary outcome [2] 0 0
Maximum Serum Concentration (Cmax) of Tiragolumab
Timepoint [2] 0 0
Day 1 up to 8 years
Secondary outcome [3] 0 0
Minimum Serum Concentration (Cmin) of Tiragolumab
Timepoint [3] 0 0
Day 1 up to 8 years
Secondary outcome [4] 0 0
Clearance (CL) of Tiragolumab
Timepoint [4] 0 0
Day 1 up to 8 years
Secondary outcome [5] 0 0
Volume of Distribution at Steady State (Vss) of Tiragolumab
Timepoint [5] 0 0
Day 1 up to 8 years
Secondary outcome [6] 0 0
Cmax of Atezolizumab
Timepoint [6] 0 0
Day 1 up to 8 years
Secondary outcome [7] 0 0
Cmin of Atezolizumab
Timepoint [7] 0 0
Day 1 up to 8 years
Secondary outcome [8] 0 0
Plasma Concentration of Cisplatin
Timepoint [8] 0 0
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Secondary outcome [9] 0 0
Plasma Concentration of Carboplatin
Timepoint [9] 0 0
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Secondary outcome [10] 0 0
Plasma Concentration of Pemetrexed
Timepoint [10] 0 0
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Secondary outcome [11] 0 0
Plasma Concentration of Paclitaxel
Timepoint [11] 0 0
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Secondary outcome [12] 0 0
Plasma Concentration of Etoposide
Timepoint [12] 0 0
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Secondary outcome [13] 0 0
Plasma Concentration of Capecitabine
Timepoint [13] 0 0
Pre-dose (5 min) on Day 1 of Cycle 1 and post-dose (2 hours) on Day 1 of Cycle 3 (cycle length 21 days)
Secondary outcome [14] 0 0
Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Timepoint [14] 0 0
From Baseline until disease progression (up to 8 years)
Secondary outcome [15] 0 0
Duration of Objective Response (DOR) According to RECIST Version 1.1
Timepoint [15] 0 0
From Baseline until disease progression (up to 8 years)
Secondary outcome [16] 0 0
Progression-Free Survival (PFS) According to RECIST Version 1.1
Timepoint [16] 0 0
From Baseline until disease progression (up to 8 years)
Secondary outcome [17] 0 0
Overall survival (OS) According to RECIST Version 1.1
Timepoint [17] 0 0
Baseline until death from any cause (up to approximately 8 years)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Kinghorn Cancer Centre; St Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Center - North Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3051 - North Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
France
State/province [10] 0 0
Bordeaux
Country [11] 0 0
France
State/province [11] 0 0
Lyon
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Toulouse
Country [14] 0 0
France
State/province [14] 0 0
Villejuif
Country [15] 0 0
Japan
State/province [15] 0 0
Tokyo
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Seoul
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Spain
State/province [18] 0 0
Navarra
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Spain
State/province [20] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.