Clinical Trial: NCT02794571 - My Cancer Genome

NCT02794571

Description:

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.

Related Conditions:

Malignant Solid Tumor

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02794571

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: GO30103
SECONDARY ID: 2016-000944-33
NCT ID: NCT02794571

Conditions

Advanced/Metastatic Tumors

Interventions

Drug	Synonyms	Arms
Atezolizumab	MPDL3280A, RO5541267, Tecentriq	Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A
Tiragolumab	MTIG7192A, RO7092284	Phase Ia Dose-Escalation Stage: Tiragolumab
Carboplatin		Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A
Cisplatin		Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A
Pemetrexed		Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A
Paclitaxel		Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B
Etoposide		Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C
Capecitabine		Phase Ib Chemotherapy Dose-Expansion Stage: Cohort D
Bevacizumab		Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC1
Pembrolizumab		Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC2

Purpose

Trial Arms

Name	Type	Description	Interventions
Phase Ia Dose-Escalation Stage: Tiragolumab	Experimental	Cohorts of at least 3 participants each will be treated with escalating doses of tiragolumab.	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.	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.	Atezolizumab 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.	Atezolizumab 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.	Atezolizumab Tiragolumab Carboplatin Cisplatin 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).	Atezolizumab Tiragolumab Carboplatin 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.	Atezolizumab Tiragolumab Carboplatin Cisplatin 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.	Atezolizumab Tiragolumab 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.	Atezolizumab 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.	Atezolizumab 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.	Atezolizumab Tiragolumab 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.	Tiragolumab Pembrolizumab

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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Time Frame:	From Baseline to the end of Cycle 1 (up to 21 days)
Safety Issue:
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).

Secondary Outcome Measures

Measure:	Area Under the Concentration-Time Curve (AUC) of Tiragolumab
Time Frame:	Day 1 up to 8 years
Safety Issue:
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.

Measure:	Maximum Serum Concentration (Cmax) of Tiragolumab
Time Frame:	Day 1 up to 8 years
Safety Issue:
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.

Measure:	Minimum Serum Concentration (Cmin) of Tiragolumab
Time Frame:	Day 1 up to 8 years
Safety Issue:
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.

Measure:	Clearance (CL) of Tiragolumab
Time Frame:	Day 1 up to 8 years
Safety Issue:
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.

Measure:	Volume of Distribution at Steady State (Vss) of Tiragolumab
Time Frame:	Day 1 up to 8 years
Safety Issue:
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.

Measure:	Cmax of Atezolizumab
Time Frame:	Day 1 up to 8 years
Safety Issue:
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.

Measure:	Cmin of Atezolizumab
Time Frame:	Day 1 up to 8 years
Safety Issue:
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.

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	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)
Safety Issue:
Description:

Measure:	Duration of Objective Response (DOR) According to RECIST Version 1.1
Time Frame:	From Baseline until disease progression (up to 8 years)
Safety Issue:
Description:

Measure:	Progression-Free Survival (PFS) According to RECIST Version 1.1
Time Frame:	From Baseline until disease progression (up to 8 years)
Safety Issue:
Description:

Measure:	Overall survival (OS) According to RECIST Version 1.1
Time Frame:	Baseline until death from any cause (up to approximately 8 years)
Safety Issue:
Description:

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Genentech, Inc.

Last Updated

May 20, 2021

Clinical Trials /

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