- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04158583
A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors
July 19, 2023 updated by: Hoffmann-La Roche
An Open-Label, Multicenter Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7296682, A CD25-Targeting, T-Regulatory Cell Depleting Antibody in Participants With Advanced and/or Metastatic Solid Tumor
This study was planned to evaluate the safety and tolerability of RO7296682 in participants with advanced solid tumors.
Study Overview
Detailed Description
A Phase 1, open-label, dose-escalation study designed to evaluate the safety and tolerability of RO7296682 in participants with advanced and/or metastatic solid tumors.
RO7296682 was administered by IV infusion Q3W.
This entry-into-human study is divided into a dose-escalation stage (Part A) and a dose expansion stage (Part B).
Study Type
Interventional
Enrollment (Actual)
76
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Victoria
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Melbourne, Victoria, Australia, 3000
- Peter MacCallum Cancer Centre; Medical Oncology
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Bruxelles, Belgium, 1200
- Cliniques Universitaires St-Luc
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 4E6
- BC Cancer Agency - Vancouver
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Ontario
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Ottawa, Ontario, Canada, K2H 6C2
- The Ottawa Hospital Cancer Centre
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Toronto, Ontario, Canada, M5G 1Z5
- Princess Margaret Cancer Centre
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København Ø, Denmark, 2100
- Rigshospitalet; Onkologisk Klinik
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Barcelona, Spain, 08035
- Vall d?Hebron Institute of Oncology (VHIO), Barcelona
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Madrid, Spain, 28040
- START Madrid-FJD, Hospital Fundacion Jimenez Diaz
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Madrid, Spain, 28050
- START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
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Valencia, Spain, 46010
- Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
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Navarra
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Pamplona, Navarra, Spain, 31008
- Clinica Universitaria de Navarra
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Diagnosis of advanced and/or metastatic solid tumors who have progressed on all standard therapies, are intolerant to Standard-Of-Care (SOC), and/or are non-amenable to SOC. Participants whose tumors have known sensitizing mutation must have experienced disease progression (during or after treatment) or intolerance to treatment with a respective targeted therapy.
- Measurable disease according to response evaluation criteria in solid tumors (RECIST) v1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Able to provide the most recent archival tumor tissue samples.
- Adequate cardiovascular, haematological, liver and renal function.
- Participants on therapeutic anticoagulation must be on a stable anticoagulant regimen.
- Women of Childbearing Potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods.
- Men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods and refrain from donating sperm.
Exclusion Criteria:
- Pregnancy, lactation, or breastfeeding.
- Known hypersensitivity to any of the components of RO7296682, including but not limited to hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
- History or clinical evidence of central nervous system (CNS) primary tumors or metastases.
- Participants with another invasive malignancy in the last two years.
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.
- Participants with known active or uncontrolled infection.
- Positive human immunodeficiency virus (HIV) test at screening.
- Positive for Hepatitis B and C.
- Vaccination with live vaccines within 28 days prior to C1D1.
- Major surgical procedure or significant traumatic injury within 28 days prior to first RO7296682 infusion.
- Participants with wound healing complications.
- Dementia or altered mental status that would prohibit informed consent.
- History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (drug rash with eosinophilia and systemic symptoms).
- Active or history of autoimmune disease or immune deficiency.
- Prior treatment with checkpoint inhibitors (CPIs) (e.g. anti-CTLA4, anti-PD1, anti-PDL1), immunomodulatory monoclonal antibodies (mAbs) and/or mAb-derived therapies (approved or investigational) is approved.
- Prior treatment with a CC chemokine receptor 4 (CCR4)-targeting (e.g. mogamulizumab) or a CD25-targeting agent (e.g. basiliximab) is prohibited.
- Treatment with standard radiotherapy, any chemotherapeutic agent, targeted therapy or treatment with any other investigational drug (defined as treatment for which there is currently no regulatory authority-approved indication) within 28 days or 5 half-lives of the drug (whichever is shorter), prior to the first RO7296882 administration on C1D1.
- Radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy (for which no wash out period is required).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Part A: Cohort 1 RO7296682 0.3 mg Q3W
Participants with non-small cell lung cancer (NSCLC), melanoma (MEL), head and neck squamous cell carcinoma (HNSCC), ovarian cancer (OvC), triple-negative breast cancer (TNBC), and esophageal carcinoma (EsC) received RO7296682 0.3 milligram (mg) intravenous (IV) infusion on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, every 3 weeks (Q3W).
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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Experimental: Part A: Cohort 2 RO7296682 1 mg Q3W
Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 1 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W.
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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Experimental: Part A: Cohort 3 RO7296682 2 mg Q3W
Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 2 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W.
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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Experimental: Part A: Cohort 4 RO7296682 6 mg Q3W
Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 6 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W.
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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Experimental: Part A: Cohort 5 RO7296682 18 mg Q3W
Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 18 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W.
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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Experimental: Part A: Cohort 6 RO7296682 35 mg Q3W
Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 35 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W.
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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Experimental: Part A: Cohort 7 RO7296682 70 mg Q3W
Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 70 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W.
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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Experimental: Part A: Cohort 8 RO7296682 100 mg Q3W
Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 100 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W.
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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Experimental: Part A: Cohort 9 RO7296682 165 mg Q3W
Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 165 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W.
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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Experimental: Part A: Cohort 10 RO7296682 20 mg Q3W
Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 20 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W.
Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade >=4, IRR; Grade >=4, immune-mediated adverse events; Grade >=4) were discontinued from study treatment.
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RO7296682 will be administered by the schedules specified in the respective arms.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0)
Time Frame: From signing of informed consent form (ICF) until last follow-up visit (Up to approximately 2 years 7 months)
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An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product.
An AE does not necessarily have to have a causal relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.
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From signing of informed consent form (ICF) until last follow-up visit (Up to approximately 2 years 7 months)
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Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Up to 28 days
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A DLT was defined as occurrence of a clinically significant adverse event (AE) from first administration of RO7296682 up to 7 days after second administration of RO7296682.
DLTs were defined as following: 1) Hematologic toxicities - Grade 4 neutropenia lasting >=7 days, Grade >=3 febrile neutropenia, Grade 4 thrombocytopenia lasting >=48 hours, Grade 3 thrombocytopenia associated with bleeding episode and Grade 4 anemia 2) Nonhematologic toxicities - Grade 3 nausea, vomiting or diarrhea, Grade >=3 fatigue, Grade 3 arthralgia, fever >40 degree Celsius occurs within 48 hours, Grade >+ laboratory abnormalities, Grade 3 autoimmune thyroiditis or other endocrine abnormalities, Grade 3 tumor flare, Grade 3 transient increase of bilirubin in participants with liver lesions, transaminases (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) and/or gamma-glutamyl transferase (GGT) and any other RO7296682-related toxicity significant enough to be qualified as DLT.
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Up to 28 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Objective Response Rate (ORR)
Time Frame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months )
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ORR is defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigators' assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to < 10 millimeters (mm).
PR is defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters in the absence of CR.
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From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months )
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Disease Control Rate (DCR)
Time Frame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
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DCR defined as the percentage of participants with an overall response of either CR, PR, or stable disease (SD), based on Investigators' assessment using RECIST Version 1.1.
CR is defined as disappearance of all target lesions.
any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.
PD is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for (PD).
PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline (nadir).
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From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
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Duration of Response (DOR)
Time Frame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
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DOR is defined as the time from first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1.
or death from any cause, whichever occurs first.
Objective response is defined as the percentage of participants having a CR or PR as determined by investigators' assessment of radiographic disease per RECIST v1.1.
CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to < 10 mm.
PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters in the absence of CR.
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From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
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On-Treatment Progression Free Survival (PFS)
Time Frame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
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The PFS on treatment was defined as the time from study treatment initiation (Cycle 1 Day 1, (1 cycle=21 days) ) to the first occurrence of documented disease progression based on RECIST Version 1.1 Investigator's assessment, or death from any cause, whichever occurred first.
For participants who did not have documented progressive disease or death (within 30 days from last study treatment) during the study, PFS was censored at the day of the last tumor assessment.
Participants without any post baseline assessments or with all post-baseline assessments having unknown result/response but known to be alive at the clinical cut off for the analysis would be censored at the date of study treatment initiation plus one day.
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From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
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Area Under the Serum Concentration Time Curve (AUC) of RO7296682
Time Frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Minimum Serum Concentration (Cmin) of RO7296682
Time Frame: Cycles 3 or 4 (Cycle length = 21 days)
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Cycles 3 or 4 (Cycle length = 21 days)
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Maximum Serum Concentration (Cmax) of RO7296682
Time Frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Total Clearance (CL) of RO7296682
Time Frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Volume of Distribution at Steady State (Vss) of RO7296682
Time Frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Terminal Half-Life (T1/2) of RO7296682
Time Frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Time of Maximum Concentration (Tmax) of RO7296682
Time Frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline
Time Frame: Predose on Day 1 of each 21-day and subsequent cycles up to end of study (Up to approximately 2 years 7 months)
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Predose on Day 1 of each 21-day and subsequent cycles up to end of study (Up to approximately 2 years 7 months)
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Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline
Time Frame: Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
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Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
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Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline
Time Frame: Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
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Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 9, 2019
Primary Completion (Actual)
July 21, 2022
Study Completion (Actual)
July 21, 2022
Study Registration Dates
First Submitted
November 5, 2019
First Submitted That Met QC Criteria
November 7, 2019
First Posted (Actual)
November 12, 2019
Study Record Updates
Last Update Posted (Estimated)
March 4, 2024
Last Update Submitted That Met QC Criteria
July 19, 2023
Last Verified
July 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- WP41188
- 2019-002830-35 (EudraCT Number)
- RG6292 (Other Identifier: Hoffmann-La Roche)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org).
Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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