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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

Primary Purpose

Advanced/Metastatic Tumors

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Atezolizumab
Tiragolumab
Carboplatin
Cisplatin
Pemetrexed
Paclitaxel
Etoposide
Capecitabine
Bevacizumab
Pembrolizumab
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced/Metastatic Tumors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Honor Health Research Institute
  • University of California Los Angeles
  • Yale Cancer Center
  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Dana Farber Cancer Institute
  • Henry Ford Hospital
  • Memorial Sloan-Kettering Cancer Center
  • Tennessee Onc., PLLC - SCRI
  • Kinghorn Cancer Centre; St Vincents Hospital
  • Peter MacCallum Cancer Center
  • Princess Margaret Hospital
  • Institut Bergonie CLCC Bordeaux
  • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
  • Institut Curie
  • Institut Claudius Regaud; Departement Oncologie Medicale
  • Institut Gustave Roussy
  • National Cancer Center Hospital
  • The Cancer Institute Hospital of Japanese Foundation For Cancer Research
  • Seoul National University Hospital
  • Severance Hospital, Yonsei University Health System
  • Asan Medical Center
  • Samsung Medical Center
  • ICO L'Hospitalet; Servicio de oncologia medica
  • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Clinica Universitaria de Navarra; Servicio de oncología
  • Hospital del Mar
  • Hospital Universitario HM Sanchinarro-CIOCC; Oncología Médica
  • Hospital Clinico Universitario de Valencia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase Ia Dose-Escalation Stage: Tiragolumab

Phase Ia Dose-Expansion Stage: Tiragolumab

Phase Ib Q3W Dose-Escalation Stage: Tiragolumab+Atezolizumab

Phase Ib Q3W Dose-Expansion Stage: Tiragolumab+Atezolizumab

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 Q4W Sequential Dose-Expansion Stage: Tiragolumab+Atezolizumab

Phase Ib Q4W Coinfusion Expansion Cohort Tiragolumab+Atezolizumab

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

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

Arm Description

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

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

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.

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.

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.

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).

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.

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

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

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

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

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

Outcomes

Primary Outcome Measures

Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Percentage of Participants with Adverse Events (AEs) Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
Number of Cycles with Tiragolumab
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).
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).

Secondary Outcome Measures

Area Under the Concentration-Time Curve (AUC) of Tiragolumab
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1, Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; Ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Maximum Serum Concentration (Cmax) of Tiragolumab
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 h post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Minimum Serum Concentration (Cmin) of Tiragolumab
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 h post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Clearance (CL) of Tiragolumab
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Volume of Distribution at Steady State (Vss) of Tiragolumab
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1, Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Cmax of Atezolizumab
During Phase Ib dose-escalation stage time frame will be as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2 ,3, 4, 8, 16: 0.5 hour post-dose; Q8C, DC; every 30 days up to 120 days. During Phase Ib dose-expansion stages time frame will be as follows: Pre-dose on Day 1 of Cycles (cycle length 21/28 days) 1-4, 8, 12*, 16 (C12* only applicable to Q4W and Chemotherapy cohorts); Post-dose 0.5 hour on Day 1 of Cycles 1-4, 8, 12, 16; then Q8C until/at DC, every 30 days up to 120 days. For Q4W co-infusion cohort only: post-dose Days 2, 8 and 15 of Cycle 1.
Cmin of Atezolizumab
During Phase Ib dose-escalation stage time frame will be as follows: Pre-dose Day 1, Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2 ,3, 4, 8, 16: 0.5 hour post-dose; Q8C, DC; every 30 days up to 120 days. During Phase Ib dose-expansion stages time frame will be as follows: Pre-dose on Day 1 of Cycles (cycle length 21/28 days) 1-4,8, 12*, 16 (C12* only applicable to Q4W and Chemotherapy cohorts); Post-dose 0.5 hour on Day 1 of Cycles 1-4, 8, 12, 16; then Q8C until/at DC, every 30 days up to 120 days. For Q4W co-infusion cohort only: post-dose Days 2, 8 and 15 of Cycle 1.
Plasma Concentration of Cisplatin
Plasma Concentration of Carboplatin
Plasma Concentration of Pemetrexed
Plasma Concentration of Paclitaxel
Plasma Concentration of Etoposide
Plasma Concentration of Capecitabine
Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Duration of Objective Response (DOR) According to RECIST Version 1.1
Progression-Free Survival (PFS) According to RECIST Version 1.1
Overall survival (OS) According to RECIST Version 1.1

Full Information

First Posted
June 6, 2016
Last Updated
September 11, 2023
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02794571
Brief 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
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 23, 2016 (Actual)
Primary Completion Date
October 5, 2024 (Anticipated)
Study Completion Date
October 5, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced/Metastatic Tumors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
518 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase Ia Dose-Escalation Stage: Tiragolumab
Arm Type
Experimental
Arm Description
Cohorts of at least 3 participants each will be treated with escalating doses of tiragolumab.
Arm Title
Phase Ia Dose-Expansion Stage: Tiragolumab
Arm Type
Experimental
Arm Description
Participants will be treated with tiragolumab at or below the maximum tolerated dose (MTD) or maximum administered dose (MAD) in the study.
Arm Title
Phase Ib Q3W Dose-Escalation Stage: Tiragolumab+Atezolizumab
Arm Type
Experimental
Arm 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.
Arm Title
Phase Ib Q3W Dose-Expansion Stage: Tiragolumab+Atezolizumab
Arm Type
Experimental
Arm 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.
Arm Title
Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A
Arm Type
Experimental
Arm 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.
Arm Title
Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B
Arm Type
Experimental
Arm 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).
Arm Title
Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C
Arm Type
Experimental
Arm 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.
Arm Title
Phase Ib Chemotherapy Dose-Expansion Stage: Cohort D
Arm Type
Experimental
Arm Description
In Cohort D, participants will receive atezolizumab and tiragolumab on Day 1 and capecitabine on Day 1-14 of each 21-day cycle.
Arm Title
Phase Ib Q4W Sequential Dose-Expansion Stage: Tiragolumab+Atezolizumab
Arm Type
Experimental
Arm Description
Participants will be treated every 4 weeks (Q4W) with fixed doses of tiragolumab and atezolizumab with tiragolumab being administered prior to atezolizumab.
Arm Title
Phase Ib Q4W Coinfusion Expansion Cohort Tiragolumab+Atezolizumab
Arm Type
Experimental
Arm Description
Participants will be treated Q4W with fixed doses of tiragolumab and atezolizumab mixed and administered in one IV bag.
Arm Title
Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC1
Arm Type
Experimental
Arm Description
In Cohort NC1, participants will receive atezolizumab and tiragolumab in combination with bevacizumab on Day 1 of each 21-day cycle.
Arm Title
Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC2
Arm Type
Experimental
Arm Description
In Cohort NC2, participants will receive tiragolumab in combination with pembrolizumab on Day 1 of each 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
MPDL3280A, RO5541267, Tecentriq
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tiragolumab
Other Intervention Name(s)
MTIG7192A, RO7092284
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Etoposide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab 15 mg/kg IV infusion will be administered on Day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Pembrolizumab 200 mg IV infusion will be administered on Day 1 of each 21-day cycle after treatment with tiragolumab.
Primary Outcome Measure Information:
Title
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Time Frame
From Baseline to the end of Cycle 1 (up to 21 days)
Title
Percentage of Participants with Adverse Events (AEs) Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0
Time Frame
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)
Title
Number of Cycles with Tiragolumab
Time Frame
From Baseline to last dose (up to approximately 8 years)
Title
Phase Ia and Ib: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Tiragolumab
Description
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).
Time Frame
Day 1 up to 8 years
Title
Phase Ib: Percentage of Participants with ADAs to Atezolizumab
Description
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).
Time Frame
Day 1 up to 8 years
Secondary Outcome Measure Information:
Title
Area Under the Concentration-Time Curve (AUC) of Tiragolumab
Description
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1, Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; Ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Time Frame
Day 1 up to 8 years
Title
Maximum Serum Concentration (Cmax) of Tiragolumab
Description
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 h post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Time Frame
Day 1 up to 8 years
Title
Minimum Serum Concentration (Cmin) of Tiragolumab
Description
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 h post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Time Frame
Day 1 up to 8 years
Title
Clearance (CL) of Tiragolumab
Description
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Time Frame
Day 1 up to 8 years
Title
Volume of Distribution at Steady State (Vss) of Tiragolumab
Description
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1, Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
Time Frame
Day 1 up to 8 years
Title
Cmax of Atezolizumab
Description
During Phase Ib dose-escalation stage time frame will be as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2 ,3, 4, 8, 16: 0.5 hour post-dose; Q8C, DC; every 30 days up to 120 days. During Phase Ib dose-expansion stages time frame will be as follows: Pre-dose on Day 1 of Cycles (cycle length 21/28 days) 1-4, 8, 12*, 16 (C12* only applicable to Q4W and Chemotherapy cohorts); Post-dose 0.5 hour on Day 1 of Cycles 1-4, 8, 12, 16; then Q8C until/at DC, every 30 days up to 120 days. For Q4W co-infusion cohort only: post-dose Days 2, 8 and 15 of Cycle 1.
Time Frame
Day 1 up to 8 years
Title
Cmin of Atezolizumab
Description
During Phase Ib dose-escalation stage time frame will be as follows: Pre-dose Day 1, Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2 ,3, 4, 8, 16: 0.5 hour post-dose; Q8C, DC; every 30 days up to 120 days. During Phase Ib dose-expansion stages time frame will be as follows: Pre-dose on Day 1 of Cycles (cycle length 21/28 days) 1-4,8, 12*, 16 (C12* only applicable to Q4W and Chemotherapy cohorts); Post-dose 0.5 hour on Day 1 of Cycles 1-4, 8, 12, 16; then Q8C until/at DC, every 30 days up to 120 days. For Q4W co-infusion cohort only: post-dose Days 2, 8 and 15 of Cycle 1.
Time Frame
Day 1 up to 8 years
Title
Plasma Concentration of Cisplatin
Time Frame
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Title
Plasma Concentration of Carboplatin
Time Frame
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Title
Plasma Concentration of Pemetrexed
Time Frame
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Title
Plasma Concentration of Paclitaxel
Time Frame
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Title
Plasma Concentration of Etoposide
Time Frame
Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)
Title
Plasma Concentration of Capecitabine
Time Frame
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)
Title
Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame
From Baseline until disease progression (up to 8 years)
Title
Duration of Objective Response (DOR) According to RECIST Version 1.1
Time Frame
From Baseline until disease progression (up to 8 years)
Title
Progression-Free Survival (PFS) According to RECIST Version 1.1
Time Frame
From Baseline until disease progression (up to 8 years)
Title
Overall survival (OS) According to RECIST Version 1.1
Time Frame
Baseline until death from any cause (up to approximately 8 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Honor Health Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
University of California Los Angeles
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Tennessee Onc., PLLC - SCRI
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Kinghorn Cancer Centre; St Vincents Hospital
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
Peter MacCallum Cancer Center
City
North Melbourne
State/Province
Victoria
ZIP/Postal Code
3051
Country
Australia
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4X 1K9
Country
Canada
Facility Name
Institut Bergonie CLCC Bordeaux
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Facility Name
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75005
Country
France
Facility Name
Institut Claudius Regaud; Departement Oncologie Medicale
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
National Cancer Center Hospital
City
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
City
Tokyo
ZIP/Postal Code
135-8550
Country
Japan
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
ICO L'Hospitalet; Servicio de oncologia medica
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Hospital Univ Vall d'Hebron; Servicio de Oncologia
City
Sant Andreu de La Barca
State/Province
Barcelona
ZIP/Postal Code
08740
Country
Spain
Facility Name
Clinica Universitaria de Navarra; Servicio de oncología
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Hospital Universitario HM Sanchinarro-CIOCC; Oncología Médica
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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