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

Roche

Status and phase: Terminated; Phase 1

Conditions: Solid Tumors

Treatments: Drug: RO7296682

Study type: Interventional

Funder types: Industry

Identifiers

NCT04158583

2019-002830-35 (EudraCT Number)

WP41188

RG6292 (Other Identifier)

Details and patient eligibility

About

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

Full 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).

Enrollment: 76 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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76 participants in 10 patient groups

Part A: Cohort 1 RO7296682 0.3 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: RO7296682

Part A: Cohort 2 RO7296682 1 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: RO7296682

Part A: Cohort 3 RO7296682 2 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: RO7296682

Part A: Cohort 4 RO7296682 6 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: RO7296682

Part A: Cohort 5 RO7296682 18 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: RO7296682

Part A: Cohort 6 RO7296682 35 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: RO7296682

Part A: Cohort 7 RO7296682 70 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: RO7296682

Part A: Cohort 8 RO7296682 100 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: RO7296682

Part A: Cohort 9 RO7296682 165 mg Q3W

Experimental group

Description:

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.

Treatment:

Drug: RO7296682

Part A: Cohort 10 RO7296682 20 mg Q3W

Experimental group

Description:

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:

Drug: RO7296682