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

Phase 1TerminatedNCT04642365

Hoffmann-La Roche49 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumors

Interventions

RO7296682DRUG

RO7296682 will be administered as per the schedules specified in the respective arms.

AtezolizumabDRUG

Atezolizumab will be administered as per the schedules specified in the respective arms.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Locations (10)

MD Anderson Cancer Center

Houston, Texas, United States

Peter Maccallum Cancer Institute

Melbourne, Victoria, Australia

Cliniques Universitaires St-Luc

Brussels, Belgium

Outcomes

Primary Outcomes

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.

Time frame: From Day 1 up to the end of safety follow-up (up to 28.5 months)

Part 2: Number of Participants With AEs

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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