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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04158583




Registration number
NCT04158583
Ethics application status
Date submitted
5/11/2019
Date registered
12/11/2019

Titles & IDs
Public title
A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors
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
Secondary ID [1] 0 0
2019-002830-35
Secondary ID [2] 0 0
WP41188
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0)
Timepoint [1] 0 0
From signing of informed consent form (ICF) until last follow-up visit (Up to approximately 2 years 7 months)
Primary outcome [2] 0 0
Number of Participants With Dose Limiting Toxicities (DLTs)
Timepoint [2] 0 0
Up to 28 days
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months )
Secondary outcome [2] 0 0
Disease Control Rate (DCR)
Timepoint [2] 0 0
From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
Secondary outcome [4] 0 0
On-Treatment Progression Free Survival (PFS)
Timepoint [4] 0 0
From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
Secondary outcome [5] 0 0
Area Under the Serum Concentration Time Curve (AUC) of RO7296682
Timepoint [5] 0 0
Cycles 1, and 3 or 4 (Cycle length = 21 days)
Secondary outcome [6] 0 0
Minimum Serum Concentration (Cmin) of RO7296682
Timepoint [6] 0 0
Cycles 3 or 4 (Cycle length = 21 days)
Secondary outcome [7] 0 0
Maximum Serum Concentration (Cmax) of RO7296682
Timepoint [7] 0 0
Cycles 1, and 3 or 4 (Cycle length = 21 days)
Secondary outcome [8] 0 0
Total Clearance (CL) of RO7296682
Timepoint [8] 0 0
Cycles 1, and 3 or 4 (Cycle length = 21 days)
Secondary outcome [9] 0 0
Volume of Distribution at Steady State (Vss) of RO7296682
Timepoint [9] 0 0
Cycles 1, and 3 or 4 (Cycle length = 21 days)
Secondary outcome [10] 0 0
Terminal Half-Life (T1/2) of RO7296682
Timepoint [10] 0 0
Cycles 1, and 3 or 4 (Cycle length = 21 days)
Secondary outcome [11] 0 0
Time of Maximum Concentration (Tmax) of RO7296682
Timepoint [11] 0 0
Cycles 1, and 3 or 4 (Cycle length = 21 days)
Secondary outcome [12] 0 0
Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline
Timepoint [12] 0 0
Predose on Day 1 of each 21-day and subsequent cycles up to end of study (Up to approximately 2 years 7 months)
Secondary outcome [13] 0 0
Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline
Timepoint [13] 0 0
Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
Secondary outcome [14] 0 0
Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline
Timepoint [14] 0 0
Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre; Medical Oncology - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Bruxelles
Country [2] 0 0
Canada
State/province [2] 0 0
British Columbia
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Denmark
State/province [4] 0 0
København Ø
Country [5] 0 0
Spain
State/province [5] 0 0
Navarra
Country [6] 0 0
Spain
State/province [6] 0 0
Barcelona
Country [7] 0 0
Spain
State/province [7] 0 0
Madrid
Country [8] 0 0
Spain
State/province [8] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
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).


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.