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
NCT ID: NCT02794571
Last Updated: 2024-12-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
518 participants
INTERVENTIONAL
2016-05-23
2024-11-13
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Phase Ia Dose-Escalation Stage: Tiragolumab
Cohorts of at least 3 participants each will be treated with escalating doses of tiragolumab.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Pembrolizumab
Pembrolizumab 200 mg IV infusion will be administered on Day 1 of each 21-day cycle after treatment with tiragolumab.
Interventions
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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.
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.
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.
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.
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.
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.
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.
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.
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.
Pembrolizumab
Pembrolizumab 200 mg IV infusion will be administered on Day 1 of each 21-day cycle after treatment with tiragolumab.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Genentech, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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Honor Health Research Institute
Scottsdale, Arizona, United States
University of California Los Angeles
Santa Monica, California, United States
Yale Cancer Center
New Haven, Connecticut, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Tennessee Oncology - Nashville
Nashville, Tennessee, United States
Kinghorn Cancer Centre; St Vincents Hospital
Darlinghurst, New South Wales, Australia
Peter MacCallum Cancer Center
North Melbourne, Victoria, Australia
Princess Margaret Hospital
Toronto, Ontario, Canada
Institut Bergonie CLCC Bordeaux
Bordeaux, , France
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
Lyon, , France
Institut Curie
Paris, , France
Institut Claudius Regaud; Departement Oncologie Medicale
Toulouse, , France
Institut Gustave Roussy
Villejuif, , France
National Cancer Center Hospital
Tokyo, , Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
Tokyo, , Japan
Seoul National University Hospital
Seoul, , South Korea
Severance Hospital, Yonsei University Health System
Seoul, , South Korea
Asan Medical Center
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
ICO L'Hospitalet; Servicio de oncologia medica
L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Sant Andreu de la Barca, Barcelona, Spain
Clinica Universitaria de Navarra; Servicio de oncología
Pamplona, Navarre, Spain
Hospital del Mar
Barcelona, , Spain
Hospital Universitario HM Sanchinarro-CIOCC; Oncología Médica
Madrid, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Countries
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References
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Shemesh CS, Wang Y, An A, Ding H, Chan P, Liu Q, Chen YW, Wu B, Wu Q, Wang X. Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2024 Jul;94(1):45-55. doi: 10.1007/s00280-024-04650-y. Epub 2024 Mar 7.
Garralda E, Oh DY, Italiano A, Bedard PL, Delord JP, Calvo E, LoRusso P, Wainberg Z, Cervantes A, Rodriguez-Vida A, Shemesh CS, Sane R, Mendus D, Ding H, Hendricks R, Meng R, Cho BC, Kim TW, Wu B. Pharmacokinetics (PK) of Tiragolumab in First-in-Human Study in Patients with Mixed Solid Tumors (GO30103). J Clin Pharmacol. 2024 May;64(5):544-554. doi: 10.1002/jcph.2397. Epub 2024 Jan 17.
Kim TW, Bedard PL, LoRusso P, Gordon MS, Bendell J, Oh DY, Ahn MJ, Garralda E, D'Angelo SP, Desai J, Hodi FS, Wainberg Z, Delord JP, Cassier PA, Cervantes A, Gil-Martin M, Wu B, Patil NS, Jin Y, Hoang T, Mendus D, Wen X, Meng R, Cho BC. Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors: A Phase 1a/1b Nonrandomized Controlled Trial. JAMA Oncol. 2023 Nov 1;9(11):1574-1582. doi: 10.1001/jamaoncol.2023.3867.
Other Identifiers
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2016-000944-33
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GO30103
Identifier Type: -
Identifier Source: org_study_id