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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04158583
Registration number
NCT04158583
Ethics application status
Date submitted
5/11/2019
Date registered
12/11/2019
Date last updated
4/03/2024
Titles & IDs
Public title
A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors
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Scientific title
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
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Secondary ID [1]
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2019-002830-35
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Secondary ID [2]
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WP41188
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Solid Tumors
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - RO7296682
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Treatment: Drugs: RO7296682
RO7296682 will be administered by the schedules specified in the respective arms.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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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)
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Assessment method [1]
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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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Timepoint [1]
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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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Primary outcome [2]
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Number of Participants With Dose Limiting Toxicities (DLTs)
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Assessment method [2]
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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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Timepoint [2]
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Up to 28 days
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Secondary outcome [1]
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Objective Response Rate (ORR)
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Assessment method [1]
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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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Timepoint [1]
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From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months )
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Secondary outcome [2]
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Disease Control Rate (DCR)
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Assessment method [2]
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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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Timepoint [2]
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From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
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Secondary outcome [3]
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Duration of Response (DOR)
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Assessment method [3]
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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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Timepoint [3]
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From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
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Secondary outcome [4]
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On-Treatment Progression Free Survival (PFS)
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Assessment method [4]
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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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Timepoint [4]
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From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
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Secondary outcome [5]
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Area Under the Serum Concentration Time Curve (AUC) of RO7296682
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Assessment method [5]
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Timepoint [5]
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Secondary outcome [6]
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Minimum Serum Concentration (Cmin) of RO7296682
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Assessment method [6]
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Timepoint [6]
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Cycles 3 or 4 (Cycle length = 21 days)
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Secondary outcome [7]
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Maximum Serum Concentration (Cmax) of RO7296682
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Assessment method [7]
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Timepoint [7]
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Secondary outcome [8]
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Total Clearance (CL) of RO7296682
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Assessment method [8]
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Timepoint [8]
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Secondary outcome [9]
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Volume of Distribution at Steady State (Vss) of RO7296682
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Assessment method [9]
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Timepoint [9]
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Secondary outcome [10]
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Terminal Half-Life (T1/2) of RO7296682
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Assessment method [10]
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Timepoint [10]
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Secondary outcome [11]
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Time of Maximum Concentration (Tmax) of RO7296682
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Assessment method [11]
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Timepoint [11]
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Cycles 1, and 3 or 4 (Cycle length = 21 days)
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Secondary outcome [12]
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Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline
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Assessment method [12]
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Timepoint [12]
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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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Secondary outcome [13]
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Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline
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Assessment method [13]
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Timepoint [13]
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Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
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Secondary outcome [14]
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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
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Assessment method [14]
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Timepoint [14]
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Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
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Eligibility
Key inclusion criteria
1. 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.
2. Measurable disease according to response evaluation criteria in solid tumors (RECIST)
v1.1.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
4. Able to provide the most recent archival tumor tissue samples.
5. Adequate cardiovascular, haematological, liver and renal function.
6. Participants on therapeutic anticoagulation must be on a stable anticoagulant regimen.
7. Women of Childbearing Potential: Agreement to remain abstinent (refrain from
heterosexual intercourse) or use highly effective contraceptive methods.
8. Men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use
highly effective contraceptive methods and refrain from donating sperm.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Pregnancy, lactation, or breastfeeding.
2. 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.
3. History or clinical evidence of central nervous system (CNS) primary tumors or
metastases.
4. Participants with another invasive malignancy in the last two years.
5. Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results.
6. Participants with known active or uncontrolled infection.
7. Positive human immunodeficiency virus (HIV) test at screening.
8. Positive for Hepatitis B and C.
9. Vaccination with live vaccines within 28 days prior to C1D1.
10. Major surgical procedure or significant traumatic injury within 28 days prior to first
RO7296682 infusion.
11. Participants with wound healing complications.
12. Dementia or altered mental status that would prohibit informed consent.
13. History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (drug rash
with eosinophilia and systemic symptoms).
14. Active or history of autoimmune disease or immune deficiency.
15. 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.
16. Prior treatment with a CC chemokine receptor 4 (CCR4)-targeting (e.g. mogamulizumab)
or a CD25-targeting agent (e.g. basiliximab) is prohibited.
17. 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.
18. 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).
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
9/12/2019
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
21/07/2022
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Sample size
Target
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Accrual to date
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Final
76
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Peter MacCallum Cancer Centre; Medical Oncology - Melbourne
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Recruitment postcode(s) [1]
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3000 - Melbourne
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Recruitment outside Australia
Country [1]
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Belgium
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State/province [1]
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Bruxelles
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Canada
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State/province [2]
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British Columbia
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Country [3]
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Canada
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State/province [3]
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Ontario
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Country [4]
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Denmark
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State/province [4]
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København Ø
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Country [5]
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Spain
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State/province [5]
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Navarra
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Country [6]
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Spain
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State/province [6]
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Barcelona
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Country [7]
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Spain
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State/province [7]
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Madrid
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Country [8]
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Spain
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State/province [8]
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Valencia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Hoffmann-La Roche
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This study was planned to evaluate the safety and tolerability of RO7296682 in participants
with advanced solid tumors.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04158583
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Clinical Trials
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Address
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Hoffmann-La Roche
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04158583
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