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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

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

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

NCT ID

NCT02794571

First Posted

June 6, 2016

Last Updated

September 11, 2023

Sponsor

Genentech, Inc.

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

Arm Title

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A

Arm Type

Experimental

Arm Description

Arm Title

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B

Arm Type

Experimental

Arm Description

Arm Title

Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C

Arm Type

Experimental

Arm Description

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

Time Frame

Day 1 up to 8 years

Title

Phase Ib: Percentage of Participants with ADAs to Atezolizumab

Description

Time Frame

Day 1 up to 8 years

Secondary Outcome Measure Information:

Title

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

Description

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

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