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

NCT ID: NCT04158583

Last Updated: 2024-03-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-09
• Study Completion Date: 2022-07-21

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).

Conditions

Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

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.

Group Type: EXPERIMENTAL

RO7296682

Intervention Type: DRUG

RO7296682 will be administered by the schedules specified in the respective arms.

Interventions

RO7296682

RO7296682 will be administered by the schedules specified in the respective arms.

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Peter MacCallum Cancer Centre; Medical Oncology

Melbourne, Victoria, Australia

Cliniques Universitaires St-Luc

Brussels, , Belgium

BC Cancer Agency - Vancouver

Vancouver, British Columbia, Canada

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Rigshospitalet; Onkologisk Klinik

København Ø, , Denmark

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, , Spain

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, , Spain

START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

Madrid, , Spain

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Countries

Australia; Belgium; Canada; Denmark; Spain

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2019-002830-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RG6292

Identifier Type: OTHER

Identifier Source: secondary_id

WP41188

Identifier Type: -

Identifier Source: org_study_id