Hematologic Malignancies, Tumors
Conditions
Brief summary
This Phase I, multicenter, first-in-human, open-label, dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics of atezolizumab (MPDL3280A) administered as single agent to participants with locally advanced or metastatic solid malignancies or hematologic malignancies. The study will be conducted in two cohorts: Dose-escalation cohort and Expansion cohort.
Interventions
DRUGAtezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure \</= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants who are 16 to 17 years old would be enrolled after consultation with the Medical Monitor * Histologically or cytologically documented, incurable or metastatic solid tumor or hematologic malignancy that is advanced (non-resectable) or recurrent and progressing since the last anti-tumor therapy and for which no recognized standard curative therapy exists * Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report * Adequate hematologic and end organ function * Measurable disease per RECIST v1.1 for participants with solid malignancies. Disease-specific criteria for participants with prostate cancer, glioblastoma multiforme (GBM), malignant lymphoma, or multiple myeloma * For women of childbearing potential: agreement to remain abstinent or use contraceptive methods * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * For participants who will undergo serial biopsy in dose-escalation cohort, baseline tumor tissue samples should be of core needle biopsies for deep tumor tissue or organs or excisional or punch biopsies for cutaneous or subcutaneous lesions (\>/=5 millimeter \[mm\] in diameter amenable to serial biopsy)
Exclusion criteria
* Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases * Known hypersensitivity to pharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation * History or risk of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis) * History of human immunodeficiency virus (HIV) infection, active hepatitis B (chronic or acute), or hepatitis C infection * Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 * Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1 * Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Day 1 up to Day 21 |
| Maximum Tolerated Dose (MTD) of Atezolizumab | Day 1 up to Day 21 |
| Recommended Phase 2 Dose (RP2D) of Atezolizumab | Baseline up to time of determination of MTD (up to Day 21) |
| Percentage of Participants With Adverse Events | Baseline up to 90 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately [approx] 7 years [yrs]) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Serum Concentration (Cmin) of Atezolizumab | Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) | Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes \[min\]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) |
| Clearance (CL) of Atezolizumab | Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) | Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes \[min\]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) |
| Volume at Steady State (Vss) of Atezolizumab | Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) | Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes \[min\]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) |
| Percentage of Participants With Best Overall Response, Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) | — |
| Percentage of Participants With Best Overall Response, Assessed by Immune-Related Response Criteria (irRC) | From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) | — |
| PFS, Assessed by irRC | From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) | — |
| Percentage of Participants With Objective Response (CR or PR), Assessed by irRC | From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) | — |
| Duration of Objective Response, Assessed by RECIST v1.1 | Time from the first occurrence of a documented objective response to the time of relapse or death from any cause (up to approx 7 yrs) | — |
| Duration of Objective Response, Assessed by irRC | Time from the first occurrence of a documented objective response to the time of relapse or death from any cause (up to approx 7 yrs) | — |
| Progression-Free Survival (PFS), Assessed by RECIST v1.1 | From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) | — |
| Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]), Assessed by RECIST v1.1 | From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) | — |
| Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) | Predose(0 hour[hr])on Day 1 of Cycles 1,2,4,8,16,17,20(Cycle length=21 days), every 8 cycles thereafter, at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure(up to approx 7 yrs) | — |
| Area Under the Concentration-Time Curve (AUC) of Atezolizumab | Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) | Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes \[min\]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohort: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) |
| Maximum Serum Concentration (Cmax) of Atezolizumab | Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) | Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes \[min\]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) |
Countries
France, Spain, United Kingdom, United States
Outcome results
None listed