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

• ClinicalTrials.gov Identifier: NCT04642365
• Recruitment Status: Recruiting
• First Posted: November 24, 2020
• Last Update Posted: February 10, 2021
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: November 23, 2020
• First Posted Date: November 24, 2020
• Last Update Posted Date: February 10, 2021
• Actual Study Start Date: January 4, 2021
• Estimated Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 23, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 23, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Tolerability of RO7296682 in Combination With Atezolizumab in Participants With Advanced Solid Tumors.
• Official Title: 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
• Brief Summary: This study will evaluate the safety, tolerability and preliminary anti-tumor activity of RO7296682 in combination with Atezolizumab in participants with advanced solid tumors.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

• Drug: RO7296682
  RO7296682 will be administered as per the schedules specified in the respective arms.
• Drug: Atezolizumab
  Atezolizumab will be administered as per the schedules specified in the respective arms.

Study Arms

• 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.
  Interventions:

  • Drug: RO7296682
  • Drug: Atezolizumab
• 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.
  Interventions:

  • Drug: RO7296682
  • Drug: Atezolizumab
• 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.
  Interventions:

  • Drug: RO7296682
  • Drug: Atezolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 23, 2020): 160
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2023
• Estimated Primary Completion Date: December 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: BP42595 http://www.roche.com/about_roche/roche_worldwide.htm; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, Belgium, Canada, Denmark, Spain

Administrative Information

• NCT Number: NCT04642365
• Other Study ID Numbers: BP42595; 2020-003164-82 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• 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).

• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: February 2021