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

NCT04158583 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: WP411882019-002830-35RG6292
• Study Type: interventional
• Target: 76
• Locations: 5 countries
• Sites: 11

Brief Summary

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

Conditions

Solid Tumors

Keywords

RG6292

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 28 days

Secondary Outcomes (14)

• Objective Response Rate (ORR)

  From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months )

• Disease Control Rate (DCR)

  From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)

• Duration of Response (DOR)

  From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)

• On-Treatment Progression Free Survival (PFS)

  From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)

• Area Under the Serum Concentration Time Curve (AUC) of RO7296682

  Cycles 1, and 3 or 4 (Cycle length = 21 days)

Study Arms (10)

Part A: Cohort 1 RO7296682 0.3 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Part A: Cohort 2 RO7296682 1 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Part A: Cohort 3 RO7296682 2 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Part A: Cohort 4 RO7296682 6 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Part A: Cohort 5 RO7296682 18 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Part A: Cohort 6 RO7296682 35 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Part A: Cohort 7 RO7296682 70 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Part A: Cohort 8 RO7296682 100 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Part A: Cohort 9 RO7296682 165 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Part A: Cohort 10 RO7296682 20 mg Q3W

EXPERIMENTAL

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.

Drug: RO7296682

Interventions

RO7296682 DRUG

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

Part A: Cohort 1 RO7296682 0.3 mg Q3W; Part A: Cohort 10 RO7296682 20 mg Q3W; Part A: Cohort 2 RO7296682 1 mg Q3W; Part A: Cohort 3 RO7296682 2 mg Q3W; Part A: Cohort 4 RO7296682 6 mg Q3W; Part A: Cohort 5 RO7296682 18 mg Q3W; Part A: Cohort 6 RO7296682 35 mg Q3W; Part A: Cohort 7 RO7296682 70 mg Q3W; Part A: Cohort 8 RO7296682 100 mg Q3W; Part A: Cohort 9 RO7296682 165 mg Q3W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Measurable disease according to response evaluation criteria in solid tumors (RECIST) v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Able to provide the most recent archival tumor tissue samples.
• Adequate cardiovascular, haematological, liver and renal function.
• Participants on therapeutic anticoagulation must be on a stable anticoagulant regimen.
• Women of Childbearing Potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods.
• Men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods and refrain from donating sperm.

You may not qualify if:

• Pregnancy, lactation, or breastfeeding.
• 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.
• History or clinical evidence of central nervous system (CNS) primary tumors or metastases.
• Participants with another invasive malignancy in the last two years.
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.
• Participants with known active or uncontrolled infection.
• Positive human immunodeficiency virus (HIV) test at screening.
• Positive for Hepatitis B and C.
• Vaccination with live vaccines within 28 days prior to C1D1.
• Major surgical procedure or significant traumatic injury within 28 days prior to first RO7296682 infusion.
• Participants with wound healing complications.
• Dementia or altered mental status that would prohibit informed consent.
• History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (drug rash with eosinophilia and systemic symptoms).
• Active or history of autoimmune disease or immune deficiency.
• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (11)

Peter MacCallum Cancer Centre; Medical Oncology

Melbourne, Victoria, 3000, Australia

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

BC Cancer Agency - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K2H 6C2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

Rigshospitalet; Onkologisk Klinik

København Ø, 2100, Denmark

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

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

Barcelona, 08035, Spain

Location

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, 46010, Spain

Location

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-La-Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2019
• First Posted: November 12, 2019
• Study Start: December 9, 2019
• Primary Completion: July 21, 2022
• Study Completion: July 21, 2022
• Last Updated: March 4, 2024
• Results First Posted: March 4, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); AU (1); CA (3); DK (1); ES (5)