Advanced/Metastatic Tumors Clinical Trial
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
| Verified date | May 2024 |
| Source | Genentech, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 518 |
| Est. completion date | October 5, 2024 |
| Est. primary completion date | October 5, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Kinghorn Cancer Centre; St Vincents Hospital | Darlinghurst | New South Wales |
| Australia | Peter MacCallum Cancer Center | North Melbourne | Victoria |
| Canada | Princess Margaret Hospital | Toronto | Ontario |
| France | Institut Bergonie CLCC Bordeaux | Bordeaux | |
| France | Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes | Lyon | |
| France | Institut Curie | Paris | |
| France | Institut Claudius Regaud; Departement Oncologie Medicale | Toulouse | |
| France | Institut Gustave Roussy | Villejuif | |
| Japan | National Cancer Center Hospital | Tokyo | |
| Japan | The Cancer Institute Hospital of Japanese Foundation For Cancer Research | Tokyo | |
| Korea, Republic of | Asan Medical Center | Seoul | |
| Korea, Republic of | Samsung Medical Center | Seoul | |
| Korea, Republic of | Seoul National University Hospital | Seoul | |
| Korea, Republic of | Severance Hospital, Yonsei University Health System | Seoul | |
| Spain | Hospital del Mar | Barcelona | |
| Spain | ICO L'Hospitalet; Servicio de oncologia medica | L'Hospitalet de Llobregat | Barcelona |
| Spain | Hospital Universitario HM Sanchinarro-CIOCC; Oncología Médica | Madrid | |
| Spain | Clinica Universitaria de Navarra; Servicio de oncología | Pamplona | Navarra |
| Spain | Hospital Univ Vall d'Hebron; Servicio de Oncologia | Sant Andreu de La Barca | Barcelona |
| Spain | Hospital Clinico Universitario de Valencia | Valencia | |
| United States | Johns Hopkins Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Henry Ford Hospital | Detroit | Michigan |
| United States | Tennessee Oncology - Nashville | Nashville | Tennessee |
| United States | Yale Cancer Center | New Haven | Connecticut |
| United States | Memorial Sloan-Kettering Cancer Center | New York | New York |
| United States | University of California Los Angeles | Santa Monica | California |
| United States | Honor Health Research Institute | Scottsdale | Arizona |
| Lead Sponsor | Collaborator |
|---|---|
| Genentech, Inc. |
United States, Australia, Canada, France, Japan, Korea, Republic of, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of Participants with Dose-Limiting Toxicities (DLTs) | From Baseline to the end of Cycle 1 (up to 21 days) | ||
| Primary | 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) | ||
| Primary | Number of Cycles with Tiragolumab | From Baseline to last dose (up to approximately 8 years) | ||
| Primary | 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 | |
| Primary | 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 | 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. |
Day 1 up to 8 years | |
| Secondary | 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. |
Day 1 up to 8 years | |
| Secondary | 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. |
Day 1 up to 8 years | |
| Secondary | 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. |
Day 1 up to 8 years | |
| Secondary | 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. |
Day 1 up to 8 years | |
| Secondary | 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. |
Day 1 up to 8 years | |
| Secondary | 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. |
Day 1 up to 8 years | |
| Secondary | Plasma Concentration of Cisplatin | Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days) | ||
| Secondary | Plasma Concentration of Carboplatin | Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days) | ||
| Secondary | Plasma Concentration of Pemetrexed | Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days) | ||
| Secondary | Plasma Concentration of Paclitaxel | Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days) | ||
| Secondary | Plasma Concentration of Etoposide | Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days) | ||
| Secondary | Plasma Concentration of Capecitabine | 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) | ||
| Secondary | Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | From Baseline until disease progression (up to 8 years) | ||
| Secondary | Duration of Objective Response (DOR) According to RECIST Version 1.1 | From Baseline until disease progression (up to 8 years) | ||
| Secondary | Progression-Free Survival (PFS) According to RECIST Version 1.1 | From Baseline until disease progression (up to 8 years) | ||
| Secondary | Overall survival (OS) According to RECIST Version 1.1 | Baseline until death from any cause (up to approximately 8 years) |