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A Study to Evaluate the Safety and Tolerability of RO7296682 in Participants With Advanced Solid Tumors.

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04158583
Collaborator
(none)
76
Enrollment
11
Locations
2
Arms
36.7
Anticipated Duration (Months)
6.9
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety and tolerability of RO7296682 in participants with advanced solid tumors.

Condition or Disease Intervention/Treatment Phase
Phase 1

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).

Study Design

Study Type:
Interventional
Actual Enrollment :
76 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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.
Actual Study Start Date :
Dec 9, 2019
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part A

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.

Drug: RO7296682
RO7296682 will be administered as per the schedules specified in the respective arms.
Experimental: Part B

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).

Drug: RO7296682
RO7296682 will be administered as per the schedules specified in the respective arms.

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants with Adverse Events [Up to 28 months]

    Severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0)

  2. Percentage of Participants with Dose-Limiting Toxicities (DLTs) [28 Days in Part A]

Secondary Outcome Measures

  1. Objective Response Rate (ORR) [Up to 28 months]

  2. Disease Control Rate (DCR) [Up to 28 months]

  3. Duration of Response (DOR) [Up to 28 months]

  4. Progression-Free Survival (PFS) [Up to 28 months]

  5. Area under the curve (AUC) of RO7296682 [Up to 28 months]

  6. Minimum Concentration (Cmin) of RO7296682 [Up to 28 months]

  7. Maximum Concentration (Cmax) of RO7296682 [Up to 28 months]

  8. Clearance (CL) of RO7296682 [Up to 28 months]

  9. Volume of distribution at steady-state conditions (Vss) of RO7296682 [Up to 28 months]

  10. Half-life (t~1/2) of RO7296682 [Up to 28 months]

  11. Time of maximum concentration (Tmax) of RO7296682 [Up to 28 months]

  12. Incidence and titer of Anti-Drug Antibodies (ADA) during the study relative to the prevalence of ADA at baseline [Up to 28 months]

  13. Treatment-induced changes in Treg levels in blood and/or tumor as compared to baseline [Up to 28 months]

  14. Treatment-induced changes in Treg/Teff (T-regulatory cell; T-effector cell) ratio in blood and/or tumor as compared to baseline [Up to 28 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Peter MacCallum Cancer Centre; Medical Oncology Melbourne Victoria Australia 3000
2 Cliniques Universitaires St-Luc Bruxelles Belgium 1200
3 BC Cancer Agency - Vancouver Vancouver British Columbia Canada V5Z 4E6
4 The Ottawa Hospital Cancer Centre Ottawa Ontario Canada K2H 6C2
5 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 1Z5
6 Rigshospitalet; Onkologisk Klinik København Ø Denmark 2100
7 Clinica Universitaria de Navarra Pamplona Navarra Spain 31008
8 Vall d´Hebron Institute of Oncology (VHIO), Barcelona Barcelona Spain 08035
9 START Madrid-FJD, Hospital Fundacion Jimenez Diaz Madrid Spain 28040
10 START Madrid. Centro Integral Oncologico Clara Campal; CIOCC Madrid Spain 28050
11 Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia Valencia Spain 46010

Sponsors and Collaborators

  • Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT04158583
Other Study ID Numbers:
  • WP41188
  • 2019-002830-35
  • RG6292
First Posted:
Nov 12, 2019
Last Update Posted:
Jul 12, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Hoffmann-La Roche
RG6292
Additional relevant MeSH terms:
Neoplasms

Study Results

No Results Posted as of Jul 12, 2022