Solid Tumors
Conditions
Keywords
RG6292
Brief summary
This study was planned to evaluate the safety and tolerability of RO7296682 in participants with advanced solid tumors.
Detailed description
A Phase 1, open-label, dose-escalation study designed to evaluate the safety and tolerability of RO7296682 in participants with advanced and/or metastatic solid tumors. RO7296682 was administered by IV infusion Q3W. This entry-into-human study is divided into a dose-escalation stage (Part A) and a dose expansion stage (Part B).
Interventions
DRUGRO7296682
RO7296682 will be administered by the schedules specified in the respective arms.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of advanced and/or metastatic solid tumors who have progressed on all standard therapies, are intolerant to Standard-Of-Care (SOC), and/or are non-amenable to SOC. Participants whose tumors have known sensitizing mutation must have experienced disease progression (during or after treatment) or intolerance to treatment with a respective targeted therapy. 2. Measurable disease according to response evaluation criteria in solid tumors (RECIST) v1.1. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 4. Able to provide the most recent archival tumor tissue samples. 5. Adequate cardiovascular, haematological, liver and renal function. 6. Participants on therapeutic anticoagulation must be on a stable anticoagulant regimen. 7. Women of Childbearing Potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods. 8. Men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods and refrain from donating sperm.
Exclusion criteria
1. Pregnancy, lactation, or breastfeeding. 2. Known hypersensitivity to any of the components of RO7296682, including but not limited to hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies. 3. History or clinical evidence of central nervous system (CNS) primary tumors or metastases. 4. Participants with another invasive malignancy in the last two years. 5. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results. 6. Participants with known active or uncontrolled infection. 7. Positive human immunodeficiency virus (HIV) test at screening. 8. Positive for Hepatitis B and C. 9. Vaccination with live vaccines within 28 days prior to C1D1. 10. Major surgical procedure or significant traumatic injury within 28 days prior to first RO7296682 infusion. 11. Participants with wound healing complications. 12. Dementia or altered mental status that would prohibit informed consent. 13. History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or DRESS (drug rash with eosinophilia and systemic symptoms). 14. Active or history of autoimmune disease or immune deficiency. 15. Prior treatment with checkpoint inhibitors (CPIs) (e.g. anti-CTLA4, anti-PD1, anti-PDL1), immunomodulatory monoclonal antibodies (mAbs) and/or mAb-derived therapies (approved or investigational) is approved. 16. Prior treatment with a CC chemokine receptor 4 (CCR4)-targeting (e.g. mogamulizumab) or a CD25-targeting agent (e.g. basiliximab) is prohibited. 17. 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. 18. 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 |
|---|---|---|
| Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | From signing of informed consent form (ICF) until last follow-up visit (Up to approximately 2 years 7 months) | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Number of Participants With Dose Limiting Toxicities (DLTs) | Up to 28 days | A DLT was defined as occurrence of a clinically significant adverse event (AE) from first administration of RO7296682 up to 7 days after second administration of RO7296682. DLTs were defined as following: 1) Hematologic toxicities - Grade 4 neutropenia lasting \>=7 days, Grade \>=3 febrile neutropenia, Grade 4 thrombocytopenia lasting \>=48 hours, Grade 3 thrombocytopenia associated with bleeding episode and Grade 4 anemia 2) Nonhematologic toxicities - Grade 3 nausea, vomiting or diarrhea, Grade \>=3 fatigue, Grade 3 arthralgia, fever \>40 degree Celsius occurs within 48 hours, Grade \>+ laboratory abnormalities, Grade 3 autoimmune thyroiditis or other endocrine abnormalities, Grade 3 tumor flare, Grade 3 transient increase of bilirubin in participants with liver lesions, transaminases (aspartate aminotransferase \[AST\]/alanine aminotransferase \[ALT\]) and/or gamma-glutamyl transferase (GGT) and any other RO7296682-related toxicity significant enough to be qualified as DLT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months) | DOR is defined as the time from first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1. or death from any cause, whichever occurs first. Objective response is defined as the percentage of participants having a CR or PR as determined by investigators' assessment of radiographic disease per RECIST v1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters in the absence of CR. |
| On-Treatment Progression Free Survival (PFS) | From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months) | The PFS on treatment was defined as the time from study treatment initiation (Cycle 1 Day 1, (1 cycle=21 days) ) to the first occurrence of documented disease progression based on RECIST Version 1.1 Investigator's assessment, or death from any cause, whichever occurred first. For participants who did not have documented progressive disease or death (within 30 days from last study treatment) during the study, PFS was censored at the day of the last tumor assessment. Participants without any post baseline assessments or with all post-baseline assessments having unknown result/response but known to be alive at the clinical cut off for the analysis would be censored at the date of study treatment initiation plus one day. |
| Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycles 1, and 3 or 4 (Cycle length = 21 days) | — |
| Minimum Serum Concentration (Cmin) of RO7296682 | Cycles 3 or 4 (Cycle length = 21 days) | — |
| Maximum Serum Concentration (Cmax) of RO7296682 | Cycles 1, and 3 or 4 (Cycle length = 21 days) | — |
| Total Clearance (CL) of RO7296682 | Cycles 1, and 3 or 4 (Cycle length = 21 days) | — |
| Objective Response Rate (ORR) | From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months ) | ORR is defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigators' assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \< 10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters in the absence of CR. |
| Terminal Half-Life (T1/2) of RO7296682 | Cycles 1, and 3 or 4 (Cycle length = 21 days) | — |
| Time of Maximum Concentration (Tmax) of RO7296682 | Cycles 1, and 3 or 4 (Cycle length = 21 days) | — |
| Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | Predose on Day 1 of each 21-day and subsequent cycles up to end of study (Up to approximately 2 years 7 months) | — |
| Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | Baseline and at Cycle 1 Day 4 (Cycle length = 21 days) | — |
| Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Baseline and at Cycle 1 Day 4 (Cycle length = 21 days) | — |
| Volume of Distribution at Steady State (Vss) of RO7296682 | Cycles 1, and 3 or 4 (Cycle length = 21 days) | — |
| Disease Control Rate (DCR) | From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months) | DCR defined as the percentage of participants with an overall response of either CR, PR, or stable disease (SD), based on Investigators' assessment using RECIST Version 1.1. CR is defined as disappearance of all target lesions. any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PD is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for (PD). PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline (nadir). |
Countries
Australia, Belgium, Canada, Denmark, Spain
Participant flow
Recruitment details
Participants took part in Part A of the study at 11 centers in Australia, Belgium, Canada, Denmark and Spain from 09 December 2019 to 21 July 2022. The study was terminated before Part B was initiated.
Pre-assignment details
A total of 76 participants with non-small cell lung cancer (NSCLC), melanoma (MEL), head and neck squamous cell carcinoma (HNSCC), ovarian cancer (OvC), triple-negative breast cancer (TNBC), and esophageal carcinoma (EsC) were enrolled in Part A. No Participants were enrolled in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 0.3 mg IV infusion on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 5 |
| Part A: Cohort 2 RO7296682 1 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 1 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 5 |
| Part A: Cohort 3 RO7296682 2 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 2 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 6 |
| Part A: Cohort 4 RO7296682 6 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 6 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 14 |
| Part A: Cohort 5 RO7296682 18 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 18 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 8 |
| Part A: Cohort 6 RO7296682 35 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 35 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 5 |
| Part A: Cohort 7 RO7296682 70 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 70 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 15 |
| Part A: Cohort 8 RO7296682 100 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 100 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 6 |
| Part A: Cohort 9 RO7296682 165 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 165 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 6 |
| Part A: Cohort 10 RO7296682 20 mg Q3W Participants with NSCLC, MEL, HNSCC, OvC, TNBC, and EsC received RO7296682 20 mg, IV infusion, on Day 1 of Cycle 1 (1 cycle=21 days), and at subsequent cycles, Q3W. Participants experiencing toxicities fulfilling the definition of a DLT (e.g: skin toxicities; Grade \>=4, IRR; Grade \>=4, immune-mediated adverse events; Grade \>=4) were discontinued from study treatment. | 6 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Clinical Deterioration | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Clinical Progression | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Clinical Progression Disease | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 3 | 4 | 2 | 2 | 4 | 3 | 5 | 2 | 0 | 1 |
| Overall Study | Due To Patient Status | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 1 | 0 | 3 | 5 | 0 | 1 | 6 | 2 | 1 | 2 |
| Overall Study | Study Terminated by Sponsor | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Part A: Cohort 10 RO7296682 20 mg Q3W | Part A: Cohort 9 RO7296682 165 mg Q3W | Part A: Cohort 8 RO7296682 100 mg Q3W | Part A: Cohort 7 RO7296682 70 mg Q3W | Part A: Cohort 6 RO7296682 35 mg Q3W | Part A: Cohort 5 RO7296682 18 mg Q3W | Part A: Cohort 4 RO7296682 6 mg Q3W | Part A: Cohort 3 RO7296682 2 mg Q3W | Part A: Cohort 2 RO7296682 1 mg Q3W | Part A: Cohort 1 RO7296682 0.3 mg Q3W |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 10.8 | 59.5 years STANDARD_DEVIATION 14.4 | 57.0 years STANDARD_DEVIATION 14.8 | 58.8 years STANDARD_DEVIATION 10.3 | 60.3 years STANDARD_DEVIATION 11 | 55.4 years STANDARD_DEVIATION 9.2 | 60.6 years STANDARD_DEVIATION 10 | 56.4 years STANDARD_DEVIATION 9.4 | 56.8 years STANDARD_DEVIATION 17 | 57.2 years STANDARD_DEVIATION 10.9 | 62.0 years STANDARD_DEVIATION 3.1 |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 70 Participants | 5 Participants | 6 Participants | 6 Participants | 14 Participants | 5 Participants | 7 Participants | 12 Participants | 6 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Ethnicity Not Stated | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 6 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 70 Participants | 5 Participants | 5 Participants | 5 Participants | 15 Participants | 5 Participants | 6 Participants | 13 Participants | 6 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Female | 43 Participants | 4 Participants | 4 Participants | 4 Participants | 8 Participants | 3 Participants | 5 Participants | 7 Participants | 2 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 33 Participants | 2 Participants | 2 Participants | 2 Participants | 7 Participants | 2 Participants | 3 Participants | 7 Participants | 4 Participants | 2 Participants | 2 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 | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 5 | 4 / 5 | 5 / 6 | 7 / 14 | 5 / 8 | 4 / 5 | 10 / 15 | 4 / 6 | 1 / 6 | 2 / 6 |
| other Total, other adverse events | 5 / 5 | 5 / 5 | 6 / 6 | 14 / 14 | 8 / 8 | 5 / 5 | 14 / 15 | 6 / 6 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 1 / 5 | 2 / 5 | 0 / 6 | 7 / 14 | 3 / 8 | 0 / 5 | 5 / 15 | 0 / 6 | 1 / 6 | 1 / 6 |
Outcome results
Primary
Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: From signing of informed consent form (ICF) until last follow-up visit (Up to approximately 2 years 7 months)
Population: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 5 Participants |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 5 Participants |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 6 Participants |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 14 Participants |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 8 Participants |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 5 Participants |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 14 Participants |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 6 Participants |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 6 Participants |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Number of Participants With Adverse Events (AE) Determined According to The National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0) | 6 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as occurrence of a clinically significant adverse event (AE) from first administration of RO7296682 up to 7 days after second administration of RO7296682. DLTs were defined as following: 1) Hematologic toxicities - Grade 4 neutropenia lasting \>=7 days, Grade \>=3 febrile neutropenia, Grade 4 thrombocytopenia lasting \>=48 hours, Grade 3 thrombocytopenia associated with bleeding episode and Grade 4 anemia 2) Nonhematologic toxicities - Grade 3 nausea, vomiting or diarrhea, Grade \>=3 fatigue, Grade 3 arthralgia, fever \>40 degree Celsius occurs within 48 hours, Grade \>+ laboratory abnormalities, Grade 3 autoimmune thyroiditis or other endocrine abnormalities, Grade 3 tumor flare, Grade 3 transient increase of bilirubin in participants with liver lesions, transaminases (aspartate aminotransferase \[AST\]/alanine aminotransferase \[ALT\]) and/or gamma-glutamyl transferase (GGT) and any other RO7296682-related toxicity significant enough to be qualified as DLT.
Time frame: Up to 28 days
Population: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 3 Participants |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
Secondary
Area Under the Serum Concentration Time Curve (AUC) of RO7296682
Time frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
Population: Pharmacokinetic 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 12.6 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 46 |
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 26.5 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 52.4 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 46.9 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 8.7 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 39.8 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 63.5 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 104 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 33.4 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 109 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 7.2 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 280 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 29.5 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 359 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 53.6 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 1140 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 26.3 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 980 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 41.1 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 2510 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 19 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 1750 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 23.2 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 5110 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 55.1 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 3940 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 29.6 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 5920 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 38.8 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 8070 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 49.6 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 10600 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 34.4 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 11900 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 37.7 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 1 | 1040 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 22.7 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Area Under the Serum Concentration Time Curve (AUC) of RO7296682 | Cycle 3/4 | 1460 hour*micrograms per milliliter(h*μg/mL) | Geometric Coefficient of Variation 45.2 |
Secondary
Disease Control Rate (DCR)
DCR defined as the percentage of participants with an overall response of either CR, PR, or stable disease (SD), based on Investigators' assessment using RECIST Version 1.1. CR is defined as disappearance of all target lesions. any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PD is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for (PD). PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline (nadir).
Time frame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
Population: ITT population included all participants who received at least one dose of RO7296682, and who had at least one baseline and one on-study tumor assessment. Participants who received at least one dose of study drug and discontinued the study because of progression before the first on-study tumor assessment were considered as response-evaluable were included in the efficacy analyses. Participants with missing or no response assessments were classified as not evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Disease Control Rate (DCR) | 40.0 percentage of participants |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Disease Control Rate (DCR) | 20.0 percentage of participants |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Disease Control Rate (DCR) | 33.3 percentage of participants |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Disease Control Rate (DCR) | 14.3 percentage of participants |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Disease Control Rate (DCR) | 37.5 percentage of participants |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Disease Control Rate (DCR) | 20.0 percentage of participants |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Disease Control Rate (DCR) | 33.3 percentage of participants |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Disease Control Rate (DCR) | 33.3 percentage of participants |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Disease Control Rate (DCR) | 66.7 percentage of participants |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Disease Control Rate (DCR) | 0 percentage of participants |
Secondary
Duration of Response (DOR)
DOR is defined as the time from first occurrence of a documented objective response to disease progression as determined by the investigator according to RECIST v1.1. or death from any cause, whichever occurs first. Objective response is defined as the percentage of participants having a CR or PR as determined by investigators' assessment of radiographic disease per RECIST v1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters in the absence of CR.
Time frame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
Population: Participants who received at least one dose of study drug and discontinued the study because of progression before the first on-study tumor assessment were considered as response-evaluable were included in the efficacy analyses. No participants had an objective response, Hence DOR could not be measured.
Secondary
Maximum Serum Concentration (Cmax) of RO7296682
Time frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
Population: Pharmacokinetic 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 0.0718 μg/mL | Geometric Coefficient of Variation 26.9 |
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 0.107 μg/mL | Geometric Coefficient of Variation 51.7 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 0.256 μg/mL | Geometric Coefficient of Variation 16.1 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 0.277 μg/mL | Geometric Coefficient of Variation 8.4 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 0.505 μg/mL | Geometric Coefficient of Variation 34.3 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 0.727 μg/mL | Geometric Coefficient of Variation 42.4 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 1.79 μg/mL | Geometric Coefficient of Variation 57.5 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 2.58 μg/mL | Geometric Coefficient of Variation 80.2 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 5.22 μg/mL | Geometric Coefficient of Variation 16.3 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 5.38 μg/mL | Geometric Coefficient of Variation 31.3 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 14.0 μg/mL | Geometric Coefficient of Variation 24.2 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 9.80 μg/mL | Geometric Coefficient of Variation 29.1 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 24.0 μg/mL | Geometric Coefficient of Variation 32.9 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 22.4 μg/mL | Geometric Coefficient of Variation 25.9 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 38.2 μg/mL | Geometric Coefficient of Variation 26.7 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 41.8 μg/mL | Geometric Coefficient of Variation 18.6 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 75.9 μg/mL | Geometric Coefficient of Variation 46.2 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 72.8 μg/mL | Geometric Coefficient of Variation 33.7 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 1 | 7.46 μg/mL | Geometric Coefficient of Variation 30.6 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Maximum Serum Concentration (Cmax) of RO7296682 | Cycle 3/4 | 7.24 μg/mL | Geometric Coefficient of Variation 58.3 |
Secondary
Minimum Serum Concentration (Cmin) of RO7296682
Time frame: Cycles 3 or 4 (Cycle length = 21 days)
Population: Pharmacokinetic 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | NA μg/mL | — |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | 0.0546 μg/mL | — |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | 0.0858 μg/mL | Geometric Coefficient of Variation 8.4 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | 0.265 μg/mL | Geometric Coefficient of Variation 0.0519 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | 1.02 μg/mL | Geometric Coefficient of Variation 32.6 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | 1.40 μg/mL | Geometric Coefficient of Variation 29.5 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | 4.77 μg/mL | Geometric Coefficient of Variation 72 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | 5.83 μg/mL | Geometric Coefficient of Variation 126.6 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | 11.4 μg/mL | Geometric Coefficient of Variation 47.3 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Minimum Serum Concentration (Cmin) of RO7296682 | 1.11 μg/mL | Geometric Coefficient of Variation 51.8 |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline
Time frame: Predose on Day 1 of each 21-day and subsequent cycles up to end of study (Up to approximately 2 years 7 months)
Population: Immunogenicity analyses population included all participants with at least one ADA assessment, irrespective of whether or not the participant received any treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Number of Participants With Anti-Drug Antibodies (ADA) During the Study Relative to the Prevalence of ADA at Baseline | 0 Participants |
Secondary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigators' assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR is the disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \< 10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters in the absence of CR.
Time frame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months )
Population: Intent-to Treat (ITT) population included all participants who received at least one dose of RO7296682, and who had at least one baseline and one on-study tumor assessment. Participants who received at least one dose of study drug and discontinued the study because of progression before the first on-study tumor assessment were considered as response-evaluable were included in the efficacy analyses. Participants with missing or no response assessments were classified as not evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Objective Response Rate (ORR) | 0 percentage of participants |
Secondary
On-Treatment Progression Free Survival (PFS)
The PFS on treatment was defined as the time from study treatment initiation (Cycle 1 Day 1, (1 cycle=21 days) ) to the first occurrence of documented disease progression based on RECIST Version 1.1 Investigator's assessment, or death from any cause, whichever occurred first. For participants who did not have documented progressive disease or death (within 30 days from last study treatment) during the study, PFS was censored at the day of the last tumor assessment. Participants without any post baseline assessments or with all post-baseline assessments having unknown result/response but known to be alive at the clinical cut off for the analysis would be censored at the date of study treatment initiation plus one day.
Time frame: From treatment initiation until last follow-up visit (Up to approximately 2 years 7 months)
Population: ITT population included all participants who received at least one dose of RO7296682, and who had at least one baseline and one on-study tumor assessment. Participants who received at least one dose of study drug and discontinued the study because of progression before the first on-study tumor assessment were considered as response-evaluable were included in the efficacy analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | On-Treatment Progression Free Survival (PFS) | 59.0 days |
| Part A: Cohort 2 RO7296682 1 mg Q3W | On-Treatment Progression Free Survival (PFS) | 59.0 days |
| Part A: Cohort 3 RO7296682 2 mg Q3W | On-Treatment Progression Free Survival (PFS) | 43.5 days |
| Part A: Cohort 4 RO7296682 6 mg Q3W | On-Treatment Progression Free Survival (PFS) | 55.5 days |
| Part A: Cohort 5 RO7296682 18 mg Q3W | On-Treatment Progression Free Survival (PFS) | 56.5 days |
| Part A: Cohort 6 RO7296682 35 mg Q3W | On-Treatment Progression Free Survival (PFS) | 55.0 days |
| Part A: Cohort 7 RO7296682 70 mg Q3W | On-Treatment Progression Free Survival (PFS) | 57.0 days |
| Part A: Cohort 8 RO7296682 100 mg Q3W | On-Treatment Progression Free Survival (PFS) | 58.0 days |
| Part A: Cohort 9 RO7296682 165 mg Q3W | On-Treatment Progression Free Survival (PFS) | 113.0 days |
| Part A: Cohort 10 RO7296682 20 mg Q3W | On-Treatment Progression Free Survival (PFS) | 54.0 days |
Secondary
Terminal Half-Life (T1/2) of RO7296682
Time frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
Population: Pharmacokinetic 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 286 hours |
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 244 hours |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 213 hours |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 170 hours |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 382 hours |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 206 hours |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 204 hours |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 215 hours |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 265 hours |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 241 hours |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 231 hours |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 264 hours |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 356 hours |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 232 hours |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 199 hours |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 265 hours |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 198 hours |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 267 hours |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 1 | 242 hours |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Terminal Half-Life (T1/2) of RO7296682 | Cycle 3/4 | 226 hours |
Secondary
Time of Maximum Concentration (Tmax) of RO7296682
Time frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
Population: Pharmacokinetic 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 1.00 hours |
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 6.5 hours |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.05 hours |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 2.31 hours |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 5.31 hours |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 3.52 hours |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 1.08 hours |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.08 hours |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 5.36 hours |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 1.14 hours |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.08 hours |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 3.83 hours |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.20 hours |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 1.05 hours |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.20 hours |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 2.38 hours |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 4.07 hours |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 1.02 hours |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 3/4 | 21.57 hours |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Time of Maximum Concentration (Tmax) of RO7296682 | Cycle 1 | 6.68 hours |
Secondary
Total Clearance (CL) of RO7296682
Time frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
Population: Pharmacokinetic 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 23.9 milliliter per hour (mL/h) | Geometric Coefficient of Variation 46 |
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 20.7 milliliter per hour (mL/h) | Geometric Coefficient of Variation 37.1 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 25.2 milliliter per hour (mL/h) | Geometric Coefficient of Variation 63.5 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 21.3 milliliter per hour (mL/h) | Geometric Coefficient of Variation 8.7 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 18.3 milliliter per hour (mL/h) | Geometric Coefficient of Variation 7.2 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 19.3 milliliter per hour (mL/h) | Geometric Coefficient of Variation 33.4 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 16.7 milliliter per hour (mL/h) | Geometric Coefficient of Variation 53.6 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 21.4 milliliter per hour (mL/h) | Geometric Coefficient of Variation 29.5 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 15.8 milliliter per hour (mL/h) | Geometric Coefficient of Variation 26.3 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 18.4 milliliter per hour (mL/h) | Geometric Coefficient of Variation 41.1 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 13.9 milliliter per hour (mL/h) | Geometric Coefficient of Variation 19 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 20.0 milliliter per hour (mL/h) | Geometric Coefficient of Variation 23.2 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 10.9 milliliter per hour (mL/h) | Geometric Coefficient of Variation 65.1 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 17.8 milliliter per hour (mL/h) | Geometric Coefficient of Variation 29.6 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 16.9 milliliter per hour (mL/h) | Geometric Coefficient of Variation 38.8 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 12.4 milliliter per hour (mL/h) | Geometric Coefficient of Variation 49.6 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 15.5 milliliter per hour (mL/h) | Geometric Coefficient of Variation 34.4 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 13.9 milliliter per hour (mL/h) | Geometric Coefficient of Variation 37.7 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 3/4 | 13.7 milliliter per hour (mL/h) | Geometric Coefficient of Variation 45.2 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Total Clearance (CL) of RO7296682 | Cycle 1 | 19.2 milliliter per hour (mL/h) | Geometric Coefficient of Variation 22.7 |
Secondary
Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline
Time frame: Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
Population: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 1.61 percent cells per microliter (cells/µL) | Standard Deviation 0.36 |
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | 0.18 percent cells per microliter (cells/µL) | Standard Deviation 2.15 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 2.77 percent cells per microliter (cells/µL) | Standard Deviation 1.31 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | -1.22 percent cells per microliter (cells/µL) | Standard Deviation 0.88 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 1.94 percent cells per microliter (cells/µL) | Standard Deviation 1.54 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | -1.17 percent cells per microliter (cells/µL) | Standard Deviation 1.33 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 2.39 percent cells per microliter (cells/µL) | Standard Deviation 2.2 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | -1.71 percent cells per microliter (cells/µL) | Standard Deviation 1.95 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | -0.79 percent cells per microliter (cells/µL) | Standard Deviation 2.29 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 1.65 percent cells per microliter (cells/µL) | Standard Deviation 1.17 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | -3.02 percent cells per microliter (cells/µL) | Standard Deviation 0.56 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 3.40 percent cells per microliter (cells/µL) | Standard Deviation 0.25 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | -2.62 percent cells per microliter (cells/µL) | Standard Deviation 1.38 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 2.65 percent cells per microliter (cells/µL) | Standard Deviation 1.48 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 1.84 percent cells per microliter (cells/µL) | Standard Deviation 0.64 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | -1.33 percent cells per microliter (cells/µL) | Standard Deviation 0.61 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 1.92 percent cells per microliter (cells/µL) | Standard Deviation 1.51 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | -1.98 percent cells per microliter (cells/µL) | Standard Deviation 1.04 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Baseline | 2.20 percent cells per microliter (cells/µL) | Standard Deviation 1.78 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Treatment-induced Changes in Treg Levels in Blood and/or Tumor as Compared to Baseline | %CD4 Treg: Change from Baseline at Cycle 1 Day 4 | -1.28 percent cells per microliter (cells/µL) | Standard Deviation 1.1 |
Secondary
Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline
Time frame: Baseline and at Cycle 1 Day 4 (Cycle length = 21 days)
Population: Safety population included all participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not. Number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.05 ratio | Standard Deviation 0.04 |
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | 12.50 ratio | Standard Deviation 51.9 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.06 ratio | Standard Deviation 0.04 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | 19.0 ratio | Standard Deviation 131.9 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.10 ratio | Standard Deviation 0.09 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | 30.0 ratio | Standard Deviation 53.35 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.06 ratio | Standard Deviation 0.05 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | 52.30 ratio | Standard Deviation 113.88 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | -9.17 ratio | Standard Deviation 98.55 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.05 ratio | Standard Deviation 0.04 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | -5.33 ratio | Standard Deviation 33.86 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.10 ratio | Standard Deviation 0.06 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | -14.64 ratio | Standard Deviation 67.96 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.11 ratio | Standard Deviation 0.1 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.07 ratio | Standard Deviation 0.07 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | -12.33 ratio | Standard Deviation 104.22 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.04 ratio | Standard Deviation 0.04 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | 26.00 ratio | Standard Deviation 79.05 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Baseline | 0.05 ratio | Standard Deviation 0.05 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Treatment-induced Changes in Treg/Teff (T-regulatory Cell; T-effector Cell) Ratio in Blood and/or Tumor as Compared to Baseline | Treg/Teff Ratio: Change from Baseline at Cycle 1 Day 4 | -121.00 ratio | Standard Deviation 108.75 |
Secondary
Volume of Distribution at Steady State (Vss) of RO7296682
Time frame: Cycles 1, and 3 or 4 (Cycle length = 21 days)
Population: Pharmacokinetic 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 7480 milliliter (mL) | Geometric Coefficient of Variation 61.4 |
| Part A: Cohort 1 RO7296682 0.3 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 7340 milliliter (mL) | Geometric Coefficient of Variation 24.6 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 5840 milliliter (mL) | Geometric Coefficient of Variation 20.1 |
| Part A: Cohort 2 RO7296682 1 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 5410 milliliter (mL) | Geometric Coefficient of Variation 14.5 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 7570 milliliter (mL) | Geometric Coefficient of Variation 60.8 |
| Part A: Cohort 3 RO7296682 2 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 5200 milliliter (mL) | Geometric Coefficient of Variation 37.6 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 6150 milliliter (mL) | Geometric Coefficient of Variation 23.8 |
| Part A: Cohort 4 RO7296682 6 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 4710 milliliter (mL) | Geometric Coefficient of Variation 34.1 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 5520 milliliter (mL) | Geometric Coefficient of Variation 25.5 |
| Part A: Cohort 5 RO7296682 18 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 5500 milliliter (mL) | Geometric Coefficient of Variation 34.9 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 4550 milliliter (mL) | Geometric Coefficient of Variation 40.6 |
| Part A: Cohort 6 RO7296682 35 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 6920 milliliter (mL) | Geometric Coefficient of Variation 38.3 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 5030 milliliter (mL) | Geometric Coefficient of Variation 18 |
| Part A: Cohort 7 RO7296682 70 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 6140 milliliter (mL) | Geometric Coefficient of Variation 29.2 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 5020 milliliter (mL) | Geometric Coefficient of Variation 29 |
| Part A: Cohort 8 RO7296682 100 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 3850 milliliter (mL) | Geometric Coefficient of Variation 20.6 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 4510 milliliter (mL) | Geometric Coefficient of Variation 23.5 |
| Part A: Cohort 9 RO7296682 165 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 4060 milliliter (mL) | Geometric Coefficient of Variation 48.6 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 1 | 5650 milliliter (mL) | Geometric Coefficient of Variation 16.8 |
| Part A: Cohort 10 RO7296682 20 mg Q3W | Volume of Distribution at Steady State (Vss) of RO7296682 | Cycle 3/4 | 5240 milliliter (mL) | Geometric Coefficient of Variation 18.5 |