Clinical trial NCT04158583: A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: RG6292
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-11-12
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was planned to evaluate the safety and tolerability of RO7296682 in participants with advanced solid tumors.

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).

Eligibility criteria: 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.

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).

Primary outcomes:
measure: Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0)
timeFrame: From signing of informed consent form (ICF) until last follow-up visit (Up to approximately 2 years 7 months)
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months )
measure: Disease Control Rate (DCR)
timeFrame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
measure: Duration of Response (DOR)
timeFrame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
measure: On-Treatment Progression Free Survival (PFS)
timeFrame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
measure: Area Under the Serum Concentration Time Curve (AUC) of RO7296682
timeFrame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
measure: Minimum Serum Concentration (Cmin) of RO7296682
timeFrame: Cycles 3 or 4 (Cycle length = 21 days)
measure: Maximum Serum Concentration (Cmax) of RO7296682
timeFrame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
measure: Total Clearance (CL) of RO7296682
timeFrame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
measure: Volume of Distribution at Steady State (Vss) of RO7296682
timeFrame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
measure: Terminal Half-Life (T1/2) of RO7296682
timeFrame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
measure: Time of Maximum Concentration (Tmax) of RO7296682
timeFrame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
measure: Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline
timeFrame: Predose on Day 1 of each 21-day and subsequent cycles up to end of study (Up to approximately 2 years 7 months)
measure: Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline
timeFrame: Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
measure: Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline
timeFrame: Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre; Medical Oncology
state: Victoria
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: København Ø
country: Denmark
facility: Rigshospitalet; Onkologisk Klinik
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Madrid
country: Spain
facility: START Madrid-FJD, Hospital Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: