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

An Open-Label, Multicenter, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of RO7296682 in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors

This study will evaluate the safety, tolerability and preliminary anti-tumor activity of RO7296682 in combination with Atezolizumab in participants with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Atezolizumab; Drug: RO7296682

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BP42595 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Institute; Clinical Trial Unit
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency - Vancouver
  • Ontario
    • Ottawa, Ontario, Canada, K2H 6C2
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Centre
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet; Onkologisk Klinik
• Spain
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal; Servicio de Oncología
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Diagnosis of advanced and/or metastatic solid tumors who have progressed on a standard therapy, are intolerant to standard of care (SoC), and/or and non-amenable to SoC.

Participants whose tumors have known sensitizing mutations must have experienced disease progression (during or after treatment) or intolerance to treatment with a respective targeted therapy.

• Measurable disease according to 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.

Exclusion Criteria:

• Pregnancy, lactation, or breastfeeding.
• Known hypersensitivity to any of the components of RO7296682 and atezolizumab, 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.
• Participants with known active or uncontrolled infection.
• Positive 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 and atezolizumab 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 CPIs (e.g. anti-CTLA4, anti-PD1, anti-PDL1), immunomodulatory monoclonal antibodies (mAbs) and/or mAb-derived therapies (approved or investigational) is approved.
• 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.
• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I; Dose-Escalation: Mixed solid tumors participants will receive ascending doses of RO7296682 with a fixed dose of Atezolizumab, every three weeks (Q3W) until either the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is defined.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedules specified in the respective arms.; Drug: RO7296682; RO7296682 will be administered as per the schedules specified in the respective arms.
Experimental: Part II; Dose-Expansion: Will start once MTD/RP2D dose of RO7296682 in combination with Atezolizumab is defined in Part I. Participants with selected tumor types will receive a fixed dose of RO7296682 in combination with Atezolizumab.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedules specified in the respective arms.; Drug: RO7296682; RO7296682 will be administered as per the schedules specified in the respective arms.
Experimental: Part III (Exploratory); Dose-Expansion: Will start once MTD/RP2D dose of RO7296682 in combination with Atezolizumab is defined in Part I and if clinical activity is seen in this trial or in the single agent study (WP41188). Participants with selected tumor types will receive a fixed dose of RO7296682 in combination with Atezolizumab at the dosing regimen established in Part I.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedules specified in the respective arms.; Drug: RO7296682; RO7296682 will be administered as per the schedules specified in the respective arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events (AEs)	Up to 31 months
Percentage of Participants with Dose-Limiting Toxicities (DLTs)	Up to 31 months
Objective Response Rate (ORR) (Part II and III only)	Up to 31 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) (Part I only)	Up to 31 months
Disease Control Rate (DCR)	Up to 31 months
Duration of Response (DoR)	Up to 31 months
Progression-Free Survival (PFS)	Up to 31 months
Overall Survival (OS)	Up to 31 months
Area under the Curve (AUC) of RO7296682	Up to 31 months
Minimum Concentration (Cmin) of RO7296682	Up to 31 months
Maximum Concentration (Cmax) of RO7296682	Up to 31 months
Time of maximum concentration (Tmax) of RO7296682	Up to 31 months
Volume of distribution at steady-state conditions (Vss) of RO7296682	Up to 31 months
Half-life (t~1/2) of RO7296682	Up to 31 months
Treatment-induced changes in Treg levels in blood and/or tumor as compared to baseline	Up to 31 months
Treatment-induced changes in Teff/Treg (T-effector cell; T-regulatory cell) ratio in blood and/or tumor as compared to baseline	Up to 31 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Actual): January 4, 2024
• Study Completion (Actual): January 4, 2024

Study Registration Dates

• First Submitted: November 23, 2020
• First Submitted That Met QC Criteria: November 23, 2020
• First Posted (Actual): November 24, 2020

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: RG6292
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: BP42595; 2020-003164-82 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No