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

Phase 1TerminatedNCT04158583

Hoffmann-La Roche76 enrolled

Overview

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

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumors

Interventions

RO7296682DRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Locations (11)

Peter MacCallum Cancer Centre; Medical Oncology

Melbourne, Victoria, Australia

Cliniques Universitaires St-Luc

Brussels, Belgium

BC Cancer Agency - Vancouver

Vancouver, British Columbia, Canada

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Time frame: From signing of informed consent form (ICF) until last follow-up visit (Up to approximately 2 years 7 months)

Number of Participants With Dose Limiting Toxicities (DLTs)

A DLT was defined as occurrence of a clinically significant adverse event (AE) from first administration of RO7296682 up to 7 days after second administration of RO7296682. DLTs were defined as following: 1) Hematologic toxicities - Grade 4 neutropenia lasting \>=7 days, Grade \>=3 febrile neutropenia, Grade 4 thrombocytopenia lasting \>=48 hours, Grade 3 thrombocytopenia associated with bleeding episode and Grade 4 anemia 2) Nonhematologic toxicities - Grade 3 nausea, vomiting or diarrhea, Grade \>=3 fatigue, Grade 3 arthralgia, fever \>40 degree Celsius occurs within 48 hours, Grade \>+ laboratory abnormalities, Grade 3 autoimmune thyroiditis or other endocrine abnormalities, Grade 3 tumor flare, Grade 3 transient increase of bilirubin in participants with liver lesions, transaminases (aspartate aminotransferase \[AST\]/alanine aminotransferase \[ALT\]) and/or gamma-glutamyl transferase (GGT) and any other RO7296682-related toxicity significant enough to be qualified as DLT.

Time frame: Up to 28 days

Secondary Outcomes

Objective Response Rate (ORR)

ORR is defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigators' assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \< 10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters in the absence of CR.

Data from ClinicalTrials.gov

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