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

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

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Institute
• 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 2M9
      • Princess Margaret Cancer Centre
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet
• Spain
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • 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	Measure Description	Time Frame
Part 1: Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of a causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.	From Day 1 up to the end of safety follow-up (up to 28.5 months)
Part 2: Number of Participants With AEs	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of a causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.	From Day 1 up to the end of safety follow-up (up to 9.3 months)
Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)	A DLT was defined as the occurrence of any of the following toxicities related to RO7296682 and atezolizumab that occurs during the DLT assessment window and not attributable to the underlying disease or an intercurrent illness: Any Grade ≥ 3 hematologic toxicity; Any Grade ≥ 3 non-hematologic toxicity; any other RO7296682-related toxicity considered significant enough to qualify as a DLT in the opinion of the Investigator and after discussion with the Sponsor.	From Cycle 1 Day 1 up Cycle 2 Day 8 (1 Cycle = 21 days)
Part 2: Objective Response Rate (ORR)	ORR was determined as the percentage of participants with an overall response (OR) of complete response (CR) or partial response (PR) as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. Percentages have been rounded off to the nearest decimal point.	Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: ORR	ORR was determined as the percentage of participants with an OR of CR or PR as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. Percentages have been rounded off to the nearest decimal point.	From Day 1 up to end of safety follow-up (up to 28.5 months)
Part 1 and 2: Disease Control Rate (DCR)	DCR was determined as the rate of participants with an OR of either CR, PR, or stable disease (SD) rate as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Percentages have been rounded off to the nearest decimal point.	Part 1: From Day 1 up to end of safety follow-up (up to 28.5 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
Part 1 and 2: Duration of Response (DoR)	DOR was calculated for participants who had a best OR of CR/PR. DOR was defined as time from first occurrence of a documented OR until the time of documented PD or death from any cause, whichever occurs first. CR=the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR=at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without PD/death (within 30 days from last treatment) were censored on the last day of tumor assessment. Participants without post-baseline (PB) or with all PB assessments but known to be alive were censored at the date of study treatment initiation plus one day.	Part 1: From Day 1 up to end of safety follow-up (up to 28.5 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
Part 1 and 2: Progression-Free Survival (PFS)	PFS was defined as the time from study treatment initiation to the first occurrence of documented PD (per RECIST v1.1) or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Participants without PD or death (within 30 days from last treatment) were censored at the last day of tumor assessment. Participants without PB or with all PB assessments but known to be alive were censored at the date of study treatment initiation plus one day.	Part 1: From Day 1 up to end of safety follow-up (up to 28.5 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
Part 1 and 2: Overall Survival (OS)	OS was defined as the time from the first dose of study treatment to the time of death from any cause. Participants who were still alive at the time of analysis were censored at the time of their last study assessment (for active participants) or at the last date known alive (for participants in follow-up).	Part 1: From Day 1 up to end of survival follow-up (36 months); Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
Part 1 and 2: Area Under the Curve From Time of Dosing to the Last Timepoint at the End of the Dosing Period (AUClast) of RO7296682		Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Part 1 and 2: Maximum Concentration (Cmax) of RO7296682		Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682		Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682		Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Part 1 and 2: Half-life (t~1/2) of RO7296682		Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Part 1: Serum Concentration of Atezolizumab	1 Cycle = 21 days.	Predose on Day 1 of Cycles 1 to 9, 12, 14, and 17; End of infusion (EOI) on Day 1 of Cycles 1 and 4; end of study/early discontinuation (up to 28.5 months)
Part 1 and 2: Number of Participants With Treatment-induced Changes in T Regulatory C Ells (Treg) Levels in Blood and/or Tumor as Compared to Baseline	Treg depletion was defined as a reduction to 25% of baseline. As pre-specified in the protocol, the sponsor had the discretion to discontinue any part of the study at any time. On October 3, 2022, the sponsor decided to terminate Part 2 early due to recruitment challenges. As only 3 participants were enrolled in Part 2: Cohort 1, the sponsor decided not to collect and analyze data for the pharmacodynamic endpoints in Part 2.	Baseline up to 28 days post last dose (up to 24.9 months)
Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline	As pre-specified in the protocol, the sponsor had the discretion to discontinue any part of the study at any time. On October 3, 2022, the sponsor decided to terminate Part 2 early due to recruitment challenges. As only 3 participants were enrolled in Part 2: Cohort 1, the sponsor decided not to collect and analyze data for the pharmacodynamic endpoints in Part 2.	Cycle 1 Day 1 (end of infusion [EOI]); Cycle 1 Day 4 (72 hours post dose); Cycle 1 Day 8 (168 hours post dose); Cycle 1 Day 15 (336 hours post dose)

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): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 6, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: RG6292
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; 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