Description:
This study will evaluate the safety and tolerability of RO7296682 in participants with
advanced solid tumors.
Title
- Brief Title: 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, PK (Pharmacokinetics)/PD (Pharmacodynamics) of RO7296682, a T-regulatory Cell Depleting Antibody in Participants With Advanced and/or Metastatic Solid Tumors.
Clinical Trial IDs
- ORG STUDY ID:
WP41188
- SECONDARY ID:
2019-002830-35
- SECONDARY ID:
RG6292
- NCT ID:
NCT04158583
Conditions
Interventions
Drug | Synonyms | Arms |
---|
RO7296682 | | Part A |
Purpose
This study will 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 will be
administered by intravenous (IV) infusion every 3 weeks. This entry-into-human study is
divided into a dose-escalation stage (Part A) and a dose expansion stage (Part B).
Trial Arms
Name | Type | Description | Interventions |
---|
Part A | Experimental | Dose-Escalation: Mixed solid tumors participants will receive ascending doses of RO7296682. RO7296682 will be administered by intravenous (IV) infusion in a three-weekly schedule (Q3W) until either the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is defined. | |
Part B | Experimental | Dose-Expansion: Will start once MTD/RP2D dose is defined in Part A. Participants will receive a fixed dose of RO7296682 at the dosing regimen established in part A (Q3W schedule). | |
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 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 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 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).
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percentage of Participants with Adverse Events |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | Severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) |
Secondary Outcome Measures
Measure: | Objective Response Rate (ORR) |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Disease Control Rate (DCR) |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Duration of Response (DOR) |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Progression-Free Survival (PFS) |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Area under the curve (AUC) of RO7296682 |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Minimum Concentration (Cmin) of RO7296682 |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Maximum Concentration (Cmax) of RO7296682 |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Clearance (CL) of RO7296682 |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Volume of distribution at steady-state conditions (Vss) of RO7296682 |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Half-life (t~1/2) of RO7296682 |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Time of maximum concentration (Tmax) of RO7296682 |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Incidence and titer of Anti-Drug Antibodies (ADA) during the study relative to the prevalence of ADA at baseline |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Treatment-induced changes in Treg levels in blood and/or tumor as compared to baseline |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Measure: | Treatment-induced changes in Treg/Teff (T-regulatory cell; T-effector cell) ratio in blood and/or tumor as compared to baseline |
Time Frame: | Up to 28 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Trial Keywords
Last Updated
August 9, 2021