Solid Tumors
Conditions
Keywords
RG6292
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.
Interventions
DRUGRO7296682
RO7296682 will be administered as per the schedules specified in the respective arms.
DRUGAtezolizumab
Atezolizumab will be administered as per the schedules specified in the respective arms.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Adverse Events (AEs) | From Day 1 up to the end of safety follow-up (up to 28.5 months) | 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. |
| Part 2: Number of Participants With AEs | From Day 1 up to the end of safety follow-up (up to 9.3 months) | 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. |
| Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | From Cycle 1 Day 1 up Cycle 2 Day 8 (1 Cycle = 21 days) | 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. |
| Part 2: Objective Response Rate (ORR) | Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Serum Concentration of Atezolizumab | 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) | 1 Cycle = 21 days. |
| Part 1 and 2: Overall Survival (OS) | 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) | 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 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: ORR | From Day 1 up to end of safety follow-up (up to 28.5 months) | 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. |
| 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 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 | Baseline up to 28 days post last dose (up to 24.9 months) | 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. |
| Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | 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) | 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. |
| 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: Disease Control Rate (DCR) | 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) | 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 and 2: Duration of Response (DoR) | 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) | 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 and 2: Progression-Free Survival (PFS) | 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) | 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. |
Countries
Australia, Belgium, Canada, Denmark, Spain, United States
Participant flow
Recruitment details
A total of 49 participants took part in the study across 10 investigative sites in 6 countries. This study was planned to be conducted in 3 parts. Part 1 (Dose-escalation): ascending doses of RO7296682 + fixed dose of atezolizumab, Part 2 (Dose expansion): fixed dose of RO7296682 + atezolizumab and Part 3 (Exploratory). Part 2 was prematurely terminated and Part 3 was not opened for enrollment due to study termination.
Pre-assignment details
Participants with advanced and/or metastatic non-small cell lung cancer (NSCLC), melanoma (MEL), head and neck squamous cell carcinoma (HNSCC), esophageal cancer (EsC), triple-negative breast cancer (TNBC), and ovarian cancer (OvCa) who progressed on all standard therapies, were intolerant to standard of care (SoC), and/or were non-amenable to SoC/for whom SoC did not exist were enrolled in Part 1 cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg Participants received RO7296682, 0.3 mg as an IV infusion in combination with atezolizumab, 1200 mg, as an IV infusion Q3W for a maximum of 13.2 months. | 6 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg Participants received RO7296682, 1.5 mg, as an IV infusion in combination with atezolizumab, 1200 mg, as an IV infusion Q3W for a maximum of 23.7 months. | 6 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg Participants received RO7296682, 9 mg, as an IV infusion in combination with atezolizumab, 1200 mg, as an IV infusion Q3W for a maximum of 12 months. | 7 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg Participants received RO7296682, 20 mg, as an IV infusion in combination with atezolizumab, 1200 mg, as an IV infusion Q3W for a maximum of 16.6 months. | 7 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg Participants received RO7296682, 40 mg, as an IV infusion in combination with atezolizumab, 1200 mg, as an IV infusion Q3W for a maximum of 8.6 months. | 7 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg Participants received RO7296682, 80 mg, as an IV infusion in combination with atezolizumab, 1200 mg, as an IV infusion Q3W for a maximum of 24 months. | 6 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg Participants received RO7296682, 160 mg, as an IV infusion in combination with atezolizumab, 1200 mg, as an IV infusion Q3W for a maximum of 2.8 months. | 7 |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg Participants with advanced and/or metastatic NSCLC, MEL, HNSCC with inflamed tumor phenotype and acquired resistance to most recent programmed death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) treatment received RO7296682, 70 mg, as an IV infusion in combination with atezolizumab, 1200 mg, as an IV infusion Q3W for a maximum of 5.5 months. | 3 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Death | 3 | 2 | 4 | 5 | 5 | 3 | 2 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Study Terminated By Sponsor | 0 | 2 | 1 | 1 | 1 | 2 | 2 | 1 |
| Overall Study | Symptomatic Deterioration | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 10.8 | 55.3 years STANDARD_DEVIATION 8.6 | 57.1 years STANDARD_DEVIATION 9.7 | 63.0 years STANDARD_DEVIATION 10.9 | 66.4 years STANDARD_DEVIATION 9.7 | 62.0 years STANDARD_DEVIATION 13.3 | 62.6 years STANDARD_DEVIATION 10.1 | 54.5 years STANDARD_DEVIATION 12.4 | 61.7 years STANDARD_DEVIATION 10.5 |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 47 Participants | 3 Participants | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 46 Participants | 3 Participants | 7 Participants | 5 Participants | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 23 Participants | 1 Participants | 5 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 26 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 6 | 4 / 6 | 4 / 7 | 5 / 7 | 5 / 7 | 3 / 6 | 3 / 7 | 2 / 3 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 7 / 7 | 7 / 7 | 7 / 7 | 5 / 6 | 7 / 7 | 3 / 3 |
| serious Total, serious adverse events | 3 / 6 | 3 / 6 | 3 / 7 | 2 / 7 | 4 / 7 | 1 / 6 | 4 / 7 | 1 / 3 |
Outcome results
Primary
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)
Population: Safety population included all participants who received at least one dose of study treatment, whether prematurely withdrawn from the study or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Adverse Events (AEs) | 6 Participants |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Adverse Events (AEs) | 6 Participants |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Adverse Events (AEs) | 7 Participants |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Adverse Events (AEs) | 7 Participants |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Adverse Events (AEs) | 7 Participants |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Adverse Events (AEs) | 5 Participants |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Adverse Events (AEs) | 7 Participants |
Primary
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)
Population: DLT evaluable population included participants who completed the DLT period with two administrations of RO7296682/atezolizumab without DLT, or participants reported with a DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 1 Participants |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 1 Participants |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
Primary
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.
Time frame: From Day 1 up to the end of safety follow-up (up to 9.3 months)
Population: Safety population included all participants who received at least one dose of study treatment, whether prematurely withdrawn from the study or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 2: Number of Participants With AEs | 3 Participants |
Primary
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.
Time frame: Part 2: From Day 1 up to end of safety follow-up (up to 9.3 months)
Population: Efficacy population included all participants who received at least one dose of RO7296682 in combination with atezolizumab, and who had at least one baseline and one on-study tumor assessment and discontinued the study because of progression before the first on-study tumor assessment were considered response evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 2: Objective Response Rate (ORR) | 0 percentage of participants |
Secondary
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
Time frame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Population: PK-evaluable population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | 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 | Cycle 1 | 14.3 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 89.3 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | 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 | Cycle 4 | 19.4 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 79.8 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | 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 | Cycle 1 | 83.7 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 50.2 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | 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 | Cycle 4 | 109 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 34.9 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | 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 | Cycle 1 | 507 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 43.9 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | 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 | Cycle 4 | 599 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 45.3 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | 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 | Cycle 1 | 1050 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 26.9 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | 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 | Cycle 4 | 1130 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 146 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | 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 | Cycle 1 | 2100 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 50.8 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | 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 | Cycle 4 | 2780 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 82.5 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | 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 | Cycle 1 | 3860 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 22.3 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | 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 | Cycle 4 | 5460 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 8.2 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | 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 | Cycle 4 | 16700 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 0.708 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | 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 | Cycle 1 | 9890 hours*micrograms/milliliters (h*μg/mL) | Geometric Coefficient of Variation 23.8 |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | 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 | Cycle 1 | NA hours*micrograms/milliliters (h*μg/mL) | — |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | 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 | Cycle 4 | NA hours*micrograms/milliliters (h*μg/mL) | — |
Secondary
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)
Population: Efficacy population included all participants who received at least one dose of RO7296682 in combination with atezolizumab, and who had at least one baseline and one on-study tumor assessment and discontinued the study because of progression before the first on-study tumor assessment were considered response evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Disease Control Rate (DCR) | 40.0 percentage of participants |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Disease Control Rate (DCR) | 33.3 percentage of participants |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Disease Control Rate (DCR) | 57.1 percentage of participants |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Disease Control Rate (DCR) | 42.9 percentage of participants |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Disease Control Rate (DCR) | 71.4 percentage of participants |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Disease Control Rate (DCR) | 66.7 percentage of participants |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Disease Control Rate (DCR) | 14.3 percentage of participants |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Disease Control Rate (DCR) | 33.3 percentage of participants |
Secondary
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)
Population: Efficacy population included all participants who received at least one dose of RO7296682 in combination with atezolizumab, and who had at least one baseline and one on-study tumor assessment and discontinued the study because of progression before the first on-study tumor assessment were considered response evaluable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Duration of Response (DoR) | 156 days |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Duration of Response (DoR) | 364.00 days |
Secondary
Part 1 and 2: Half-life (t~1/2) of RO7296682
Time frame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Population: PK-evaluable population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 1 | 10.1 days | Geometric Coefficient of Variation 40.2 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 4 | 10.3 days | Geometric Coefficient of Variation 25.3 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 4 | 13.2 days | Geometric Coefficient of Variation 53 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 1 | 8.89 days | Geometric Coefficient of Variation 32.8 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 4 | 10.8 days | Geometric Coefficient of Variation 51.2 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 1 | 8.91 days | Geometric Coefficient of Variation 29.7 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 1 | 9.43 days | Geometric Coefficient of Variation 31.1 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 4 | 12.1 days | Geometric Coefficient of Variation 109 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 4 | 9.65 days | Geometric Coefficient of Variation 32.1 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 1 | 10.8 days | Geometric Coefficient of Variation 21.6 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 1 | 9.15 days | Geometric Coefficient of Variation 42.4 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 4 | 7.92 days | Geometric Coefficient of Variation 3.64 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 1 | 11.2 days | Geometric Coefficient of Variation 49.7 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 4 | 15.3 days | Geometric Coefficient of Variation 4.28 |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 4 | NA days | — |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Half-life (t~1/2) of RO7296682 | Cycle 1 | NA days | — |
Secondary
Part 1 and 2: Maximum Concentration (Cmax) of RO7296682
Time frame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Population: PK-evaluable population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 4 | 0.119 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 66.3 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 1 | 0.0921 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 54.1 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 4 | 0.544 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 28.8 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 1 | 0.555 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 22.2 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 1 | 3.18 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 19.3 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 4 | 3.27 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 21 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 1 | 8.23 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 32.8 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 4 | 7.82 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 40.4 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 1 | 12.7 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 40.9 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 4 | 15.3 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 43.9 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 1 | 27.3 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 34.5 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 4 | 34.2 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 27.8 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 1 | 61.7 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 17.5 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 4 | 85.2 micrograms/milliliters (μg/mL) | Geometric Coefficient of Variation 4.32 |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 1 | NA micrograms/milliliters (μg/mL) | — |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Maximum Concentration (Cmax) of RO7296682 | Cycle 4 | NA micrograms/milliliters (μg/mL) | — |
Secondary
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.
Time frame: Baseline up to 28 days post last dose (up to 24.9 months)
Population: Pharmacodynamic (PD) evaluable population included all participants who had at least one pre-dose and one post-dose PD assessment were included and analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | 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 | 1 Participants |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | 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 | 1 Participants |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | 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 | 5 Participants |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | 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 | 5 Participants |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | 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 | 7 Participants |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | 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 | 5 Participants |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | 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 | 3 Participants |
Secondary
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)
Population: Efficacy population included all participants who received at least one dose of RO7296682 in combination with atezolizumab, and who had at least one baseline and one on-study tumor assessment and discontinued the study because of progression before the first on-study tumor assessment were considered response evaluable. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Overall Survival (OS) | 181.0 days |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Overall Survival (OS) | 295.0 days |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Overall Survival (OS) | 352.0 days |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Overall Survival (OS) | 237.0 days |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Overall Survival (OS) | 353.0 days |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Overall Survival (OS) | 230.0 days |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Overall Survival (OS) | 304.0 days |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Overall Survival (OS) | 73.0 days |
Secondary
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)
Population: Efficacy population included all participants who received at least one dose of RO7296682 in combination with atezolizumab, and who had at least one baseline and one on-study tumor assessment and discontinued the study because of progression before the first on-study tumor assessment were considered response evaluable. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Progression-Free Survival (PFS) | 52.0 days |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Progression-Free Survival (PFS) | 58.0 days |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Progression-Free Survival (PFS) | 121.0 days |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Progression-Free Survival (PFS) | 59.0 days |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Progression-Free Survival (PFS) | 135.0 days |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Progression-Free Survival (PFS) | 111.0 days |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Progression-Free Survival (PFS) | 51.5 days |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Progression-Free Survival (PFS) | 69.0 days |
Secondary
Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682
Time frame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Population: PK-evaluable population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 5.53 hours |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 4 | 1.41 hours |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.15 hours |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 4 | 1.17 hours |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.17 hours |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 4 | 1.15 hours |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.92 hours |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 4 | NA hours |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.07 hours |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 4 | 1.17 hours |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.07 hours |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 4 | NA hours |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 4 | NA hours |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.13 hours |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | NA hours |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 4 | NA hours |
Secondary
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.
Time frame: 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)
Population: Pharmacodynamic (PD) evaluable population included all participants who had at least one pre-dose and one post-dose PD assessment were included and analyzed according to the treatment they actually received. Number analyzed per timepoint are unique number of participants out all the assessed participants with data available for analysis at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 8 (168 hours Post-dose) | 1.55 ratio | Standard Deviation 1.37 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 4 (72 hours Post-dose) | 0.69 ratio | Standard Deviation 0.78 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 1 (EOI) | 1.59 ratio | Standard Deviation 1.43 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 15 (336 hours Post-dose) | 1.20 ratio | Standard Deviation 0.92 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 8 (168 hours Post-dose) | 0.26 ratio | Standard Deviation 0.29 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 1 (EOI) | 0.83 ratio | Standard Deviation 0.67 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 15 (336 hours Post-dose) | 0.97 ratio | Standard Deviation 0.16 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 4 (72 hours Post-dose) | 0.17 ratio | — |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 1 (EOI) | 0.41 ratio | Standard Deviation 0.15 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 15 (336 hours Post-dose) | 0.42 ratio | Standard Deviation 0.38 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 4 (72 hours Post-dose) | 0.30 ratio | Standard Deviation 0.12 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 8 (168 hours Post-dose) | 0.29 ratio | Standard Deviation 0.22 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 15 (336 hours Post-dose) | 4.24 ratio | Standard Deviation 7.89 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 1 (EOI) | 0.27 ratio | Standard Deviation 0.2 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 4 (72 hours Post-dose) | 0.60 ratio | Standard Deviation 1.06 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 8 (168 hours Post-dose) | 0.48 ratio | Standard Deviation 0.58 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 15 (336 hours Post-dose) | 0.39 ratio | Standard Deviation 0.29 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 1 (EOI) | 0.37 ratio | Standard Deviation 0.6 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 8 (168 hours Post-dose) | 0.36 ratio | Standard Deviation 0.3 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 4 (72 hours Post-dose) | 0.19 ratio | Standard Deviation 0.22 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 4 (72 hours Post-dose) | 0.29 ratio | Standard Deviation 0.31 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 1 (EOI) | 0.68 ratio | Standard Deviation 0.92 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 8 (168 hours Post-dose) | 0.16 ratio | Standard Deviation 0.11 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 15 (336 hours Post-dose) | 0.33 ratio | Standard Deviation 0.29 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 15 (336 hours Post-dose) | 0.27 ratio | Standard Deviation 0.19 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 1 (EOI) | 0.32 ratio | Standard Deviation 0.12 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 4 (72 hours Post-dose) | 0.52 ratio | Standard Deviation 0.47 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Treatment-induced Changes in Teff (T-effector Cell)/Treg Ratio in Blood and/or Tumor as Compared to Baseline | Cycle 1 Day 8 (168 hours Post-dose) | 0.19 ratio | Standard Deviation 0.1 |
Secondary
Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682
Time frame: Cycles 1 and 4: Predose, end of infusion, and at 24, 72, 168, and 336 hours post-dose (1 Cycle = 21 days)
Population: PK-evaluable population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 4 | 5.75 Litre (L) | Geometric Coefficient of Variation 142 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 1 | 6.91 Litre (L) | Geometric Coefficient of Variation 49.8 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 1 | 5.41 Litre (L) | Geometric Coefficient of Variation 16.9 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 4 | 6.12 Litre (L) | Geometric Coefficient of Variation 19.4 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 4 | 5.59 Litre (L) | Geometric Coefficient of Variation 41.3 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 1 | 5.31 Litre (L) | Geometric Coefficient of Variation 33.6 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 1 | 5.94 Litre (L) | Geometric Coefficient of Variation 12.8 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 4 | 6.50 Litre (L) | Geometric Coefficient of Variation 10.5 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 1 | 7.29 Litre (L) | Geometric Coefficient of Variation 45.3 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 4 | 5.59 Litre (L) | Geometric Coefficient of Variation 44.8 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 1 | 6.14 Litre (L) | Geometric Coefficient of Variation 50.7 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 4 | 3.96 Litre (L) | Geometric Coefficient of Variation 24.2 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 1 | 5.84 Litre (L) | Geometric Coefficient of Variation 42.1 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 4 | 5.22 Litre (L) | Geometric Coefficient of Variation 5.82 |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 1 | NA Litre (L) | — |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1 and 2: Volume of Distribution at Steady State Conditions (Vss) of RO7296682 | Cycle 4 | NA Litre (L) | — |
Secondary
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)
Population: Efficacy population included all participants who received at least one dose of RO7296682 in combination with atezolizumab, and who had at least one baseline and one on-study tumor assessment and discontinued the study because of progression before the first on-study tumor assessment were considered response evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: ORR | 0 percentage of participants |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: ORR | 0 percentage of participants |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: ORR | 0 percentage of participants |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: ORR | 0 percentage of participants |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: ORR | 28.6 percentage of participants |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: ORR | 16.7 percentage of participants |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: ORR | 0 percentage of participants |
Secondary
Part 1: Serum Concentration of Atezolizumab
1 Cycle = 21 days.
Time frame: 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)
Population: PK-evaluable population included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 - EOI Atezo | 566 μg/mL | Geometric Coefficient of Variation 15.7 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 Predose | 180 μg/mL | Geometric Coefficient of Variation 29.2 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 17 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 14 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 12 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 9 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 8 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 - EOI | 432 μg/mL | Geometric Coefficient of Variation 25.9 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 7 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 6 Day 1 Predose | 194 μg/mL | Geometric Coefficient of Variation 11.7 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 5 Day 1 Predose | 194 μg/mL | Geometric Coefficient of Variation 40.9 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 2 Day 1 - Predose | 65.7 μg/mL | Geometric Coefficient of Variation 91.5 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | End of Study | 135 μg/mL | Geometric Coefficient of Variation 37.9 |
| Part 1: Cohort 1 - RO7296682 0.3 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 3 Day 1 Predose | 153 μg/mL | Geometric Coefficient of Variation 32.4 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 3 Day 1 Predose | 177 μg/mL | Geometric Coefficient of Variation 75.2 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 7 Day 1 Predose | 201 μg/mL | Geometric Coefficient of Variation 52.4 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 2 Day 1 - Predose | 74.6 μg/mL | Geometric Coefficient of Variation 44.6 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 - EOI | 387 μg/mL | Geometric Coefficient of Variation 17.7 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | End of Study | 105 μg/mL | Geometric Coefficient of Variation 37.4 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 - EOI Atezo | 527 μg/mL | Geometric Coefficient of Variation 8.4 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 6 Day 1 Predose | 139 μg/mL | Geometric Coefficient of Variation 112 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 9 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 Predose | 131 μg/mL | Geometric Coefficient of Variation 29.1 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 8 Day 1 Predose | 209 μg/mL | Geometric Coefficient of Variation 36 |
| Part 1: Cohort 2 - RO7296682 1.5 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 5 Day 1 Predose | 153 μg/mL | Geometric Coefficient of Variation 33 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 6 Day 1 Predose | 160 μg/mL | Geometric Coefficient of Variation 51.1 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 - EOI | 427 μg/mL | Geometric Coefficient of Variation 32.4 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 2 Day 1 - Predose | 98.2 μg/mL | Geometric Coefficient of Variation 39.4 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 3 Day 1 Predose | 89.9 μg/mL | Geometric Coefficient of Variation 98.8 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 Predose | 130 μg/mL | Geometric Coefficient of Variation 41.7 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 - EOI Atezo | 450 μg/mL | Geometric Coefficient of Variation 28 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 5 Day 1 Predose | 151 μg/mL | Geometric Coefficient of Variation 60 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 7 Day 1 Predose | 154 μg/mL | Geometric Coefficient of Variation 64.5 |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 8 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 9 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 3 - RO7296682 9 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | End of Study | 141 μg/mL | Geometric Coefficient of Variation 34 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 - EOI Atezo | NA μg/mL | — |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 6 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 5 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | End of Study | 74.1 μg/mL | Geometric Coefficient of Variation 21.1 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 3 Day 1 Predose | 84.0 μg/mL | Geometric Coefficient of Variation 49.1 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 - EOI | 374 μg/mL | Geometric Coefficient of Variation 19.5 |
| Part 1: Cohort 4 - RO7296682 20 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 2 Day 1 - Predose | 65.8 μg/mL | Geometric Coefficient of Variation 21.6 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 5 Day 1 Predose | 190 μg/mL | Geometric Coefficient of Variation 31.6 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 2 Day 1 - Predose | 58.0 μg/mL | Geometric Coefficient of Variation 72.2 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 - EOI | 363 μg/mL | Geometric Coefficient of Variation 29.5 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 9 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 7 Day 1 Predose | 265 μg/mL | Geometric Coefficient of Variation 9.61 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 3 Day 1 Predose | 121 μg/mL | Geometric Coefficient of Variation 35.5 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | End of Study | 112 μg/mL | Geometric Coefficient of Variation 16.4 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 6 Day 1 Predose | 237 μg/mL | Geometric Coefficient of Variation 23.4 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 - EOI Atezo | 512 μg/mL | Geometric Coefficient of Variation 35.9 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 Predose | 159 μg/mL | Geometric Coefficient of Variation 42.5 |
| Part 1: Cohort 5 - RO7296682 40 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 8 Day 1 Predose | 238 μg/mL | Geometric Coefficient of Variation 39 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 6 Day 1 Predose | 169 μg/mL | Geometric Coefficient of Variation 44.8 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 Predose | 115 μg/mL | Geometric Coefficient of Variation 56.4 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 - EOI Atezo | 510 μg/mL | Geometric Coefficient of Variation 14.8 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 - EOI | 379 μg/mL | Geometric Coefficient of Variation 23.3 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 5 Day 1 Predose | 162 μg/mL | Geometric Coefficient of Variation 26.4 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | End of Study | NA μg/mL | — |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 7 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 3 Day 1 Predose | 82.4 μg/mL | Geometric Coefficient of Variation 39.8 |
| Part 1: Cohort 6 - RO7296682 80 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 2 Day 1 - Predose | 67.4 μg/mL | Geometric Coefficient of Variation 50 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 Predose | NA μg/mL | — |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | End of Study | 61.3 μg/mL | Geometric Coefficient of Variation 13 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 - EOI | 492 μg/mL | Geometric Coefficient of Variation 13.1 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 - EOI Atezo | NA μg/mL | — |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 2 Day 1 - Predose | 87.9 μg/mL | Geometric Coefficient of Variation 46.3 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 4 Day 1 Predose | 260 μg/mL | Geometric Coefficient of Variation 16.9 |
| Part 1: Cohort 7 - RO7296682 160 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 3 Day 1 Predose | 181 μg/mL | Geometric Coefficient of Variation 35.1 |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 Predose | NA μg/mL | — |
| Part 2: Cohort 1 - RO7296682 70 mg + Atezolizumab 1200 mg | Part 1: Serum Concentration of Atezolizumab | Cycle 1 Day 1 - EOI | 410 μg/mL | Geometric Coefficient of Variation 25.8 |