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

NCT02794571 | Completed Phase 1

• 2 other identifiers: GO301032016-000944-33
• Study Type: interventional
• Target: 518
• Locations: 7 countries
• Sites: 28

Brief Summary

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.

Conditions

Advanced/Metastatic Tumors

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants with Dose-Limiting Toxicities (DLTs)

  From Baseline to the end of Cycle 1 (up to 21 days)

• Percentage of Participants with Adverse Events (AEs) Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0

  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)

• Number of Cycles with Tiragolumab

  From Baseline to last dose (up to approximately 8 years)

• Phase Ia and Ib: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Tiragolumab

  Phase (Ph) 1a: Pre-dose on Day 1, Cycles 1-4, 8, 16, every eight cycles (Q8C), at discontinuation (DC), every 30 days up to 120 days (cycle length 21 days); Phase 1b without Chemotherapy: Pre-dose on Day 1, Cycles 1-4, 8, then Q8C, DC (cycle length 21 days); Phase 1b (Chemotherapy Cohorts and Q4W): Pre-dose on Day 1, Cycles 1-4, 8, 12 and 16, then DC (cycle length 21/28 days).

  Day 1 up to 8 years

• Phase Ib: Percentage of Participants with ADAs to Atezolizumab

  Phase 1b (without Chemotherapy): Pre-dose on Day 1, Cycles 1-4, 8, then Q8C, at DC, every 30 days up to 120 days (cycle length 21 days); Phase 1b (Chemotherapy Cohorts and Q4W): Pre-dose on Day 1, Cycles 1-4, 8, 12 and 16, then DC (cycle length 21/28 days).

  Day 1 up to 8 years

Secondary Outcomes (17)

• Area Under the Concentration-Time Curve (AUC) of Tiragolumab

  Day 1 up to 8 years

• Maximum Serum Concentration (Cmax) of Tiragolumab

  Day 1 up to 8 years

• Minimum Serum Concentration (Cmin) of Tiragolumab

  Day 1 up to 8 years

• Clearance (CL) of Tiragolumab

  Day 1 up to 8 years

• Volume of Distribution at Steady State (Vss) of Tiragolumab

  Day 1 up to 8 years

Study Arms (12)

Phase Ia Dose-Escalation Stage: Tiragolumab

EXPERIMENTAL

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

Drug: Tiragolumab

Phase Ia Dose-Expansion Stage: Tiragolumab

EXPERIMENTAL

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

Drug: Tiragolumab

Phase Ib Q3W Dose-Escalation Stage: Tiragolumab+Atezolizumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Tiragolumab

Phase Ib Q3W Dose-Expansion Stage: Tiragolumab+Atezolizumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Tiragolumab

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Tiragolumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B

EXPERIMENTAL

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).

Drug: Atezolizumab; Drug: Tiragolumab; Drug: Carboplatin; Drug: Paclitaxel

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Tiragolumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort D

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Tiragolumab; Drug: Capecitabine

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

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Tiragolumab

Phase Ib Q4W Coinfusion Expansion Cohort Tiragolumab+Atezolizumab

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Tiragolumab

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

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Tiragolumab; Drug: Bevacizumab

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

EXPERIMENTAL

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

Drug: Tiragolumab; Drug: Pembrolizumab

Interventions

Atezolizumab DRUG

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.

Also known as: MPDL3280A, RO5541267, Tecentriq

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort D; Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC1; Phase Ib Q3W Dose-Escalation Stage: Tiragolumab+Atezolizumab; Phase Ib Q3W Dose-Expansion Stage: Tiragolumab+Atezolizumab; Phase Ib Q4W Coinfusion Expansion Cohort Tiragolumab+Atezolizumab; Phase Ib Q4W Sequential Dose-Expansion Stage: Tiragolumab+Atezolizumab

Tiragolumab DRUG

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.

Also known as: MTIG7192A, RO7092284

Phase Ia Dose-Escalation Stage: Tiragolumab; Phase Ia Dose-Expansion Stage: Tiragolumab; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort D; Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC1; Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC2; Phase Ib Q3W Dose-Escalation Stage: Tiragolumab+Atezolizumab; Phase Ib Q3W Dose-Expansion Stage: Tiragolumab+Atezolizumab; Phase Ib Q4W Coinfusion Expansion Cohort Tiragolumab+Atezolizumab; Phase Ib Q4W Sequential Dose-Expansion Stage: Tiragolumab+Atezolizumab

Carboplatin DRUG

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.

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C

Cisplatin DRUG

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.

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A; Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C

Pemetrexed DRUG

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 A

Paclitaxel DRUG

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 B

Etoposide DRUG

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 C

Capecitabine DRUG

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 Chemotherapy Dose-Expansion Stage: Cohort D

Bevacizumab DRUG

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 NC1

Pembrolizumab DRUG

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (28)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

University of California Los Angeles

Santa Monica, California, 90404, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Tennessee Oncology - Nashville

Nashville, Tennessee, 37203, United States

Location

Kinghorn Cancer Centre; St Vincents Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Peter MacCallum Cancer Center

North Melbourne, Victoria, 3051, Australia

Location

Princess Margaret Hospital

Toronto, Ontario, M4X 1K9, Canada

Location

Institut Bergonie CLCC Bordeaux

Bordeaux, 33000, France

Location

Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes

Lyon, 69008, France

Location

Institut Curie

Paris, 75005, France

Location

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Tokyo, 135-8550, Japan

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

ICO L'Hospitalet; Servicio de oncologia medica

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Sant Andreu de la Barca, Barcelona, 08740, Spain

Location

Clinica Universitaria de Navarra; Servicio de oncología

Pamplona, Navarre, 31008, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario HM Sanchinarro-CIOCC; Oncología Médica

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (3)

• 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.

  PMID: 38451273 DERIVED

• 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.

  PMID: 38105505 DERIVED

• 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.

  PMID: 37768658 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

atezolizumab; Tiragolumab; Carboplatin; Cisplatin; Pemetrexed; Paclitaxel; Etoposide; Capecitabine; Bevacizumab; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2016
• First Posted: June 9, 2016
• Study Start: May 23, 2016
• Primary Completion: November 13, 2024
• Study Completion: November 13, 2024
• Last Updated: December 5, 2024

Record last verified: 2024-12

Locations

CA (1); AU (2); FR (5); KR (4); US (8); ES (6); JP (2)