Biliary Tract Cancer, Carcinoma, Hepatocellular, Liver Metastases, Secondary Liver Cancer
Conditions
Keywords
TLR7 Agonist
Brief summary
Phase I study of RO7119929 given orally to participants with unresectable advanced or metastatic primary liver cancers and other solid tumors with predominant liver involvement. The primary objective of the study is to explore the safety and to determine the maximum tolerated dose (MTD) and/or optimal biologic dose (OBD) of RO7119929 as single agent.
Interventions
DRUGRO7119929
RO7119929 will be administered orally as a capsule
DRUGTocilizumab
Tocilizumab will be administered in case of severe steroid-refractory cytokine release syndrome. Tocilizumab will be administered as concentrate for solution for IV infusion at a dose: for participants \> 30 kg: 8 mg/kg, for participants \< 30 kg: 12mg/kg IV
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label, multi-center, single-arm, multiple-ascending dose escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of one of the following: unresectable advanced or metastatic HCC (including fibrolamellar HCC) not amenable to a curative treatment approach, unresectable advanced or metastatic intrahepatic or perihilar (Klatskin) BTC not amenable to a curative treatment approach, extrahepatic BTC or gallbladder cancer infiltrating the liver or metastasized into the liver with predominant liver disease, not amenable to a curative treatment approach, metastasized colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), Gastric cancer (GC), renal cell carcinoma (RCC), triple negative breast cancer (TNBC), cutaneous melanoma, or ocular melanoma with predominant liver disease not amenable to a curative treatment approach. Participants with other solid tumors with predominant liver disease not amenable to a curative treatment approach might be enrolled after Sponsor approval * Measurable disease with at least one measurable locally untreated liver lesion, as defined by RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Adequate hematologic and major organ functions * Participants for which there is no available standard therapy likely to confer clinical benefit, or participants who are not candidates for such available therapy * Life expectancy of ≥12 weeks, approximated with Royal Marsden Hospital score 0-1 or Gustave Roussy Immune (GRIm) score 0-1. Participants with a Royal Marsden Hospital or GRIm score of ≥2 and a life expectancy of ≥12 weeks according to the investigator's clinical judgement may be enrolled after Medical Monitor approval has been obtained. * For participants with HCC: Child-Pugh score of A6 or better
Exclusion criteria
* History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days prior to Screening * Evidence of any extra-hepatic primary tumor or metastasis requiring prompt medical intervention * Receipt of prior therapy with a TLR7/8/9 agonist and/or IFN-alpha * Prior chemotherapy, antibody, or other registered or experimental cancer treatment within 3 weeks of study Cycle 1 Day 1. Specifically, no CPI antibody is allowed to be administered within 6 weeks of study Cycle 1 Day 1 * Receipt of investigational agent for any other indication within 3 weeks of dosing * Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment * Local therapy to liver (e.g. radiofrequency ablation, percutaneuous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, and transarterial embolization) within 3 weeks prior to initiation of study treatment, radioembolization within 3 months prior to initiation of study treatment, or non-recovery from side effects of such procedure * Treatment-related toxicities from prior cancer therapy that have not resolved to \</= Grade 1 CTC AE prior to study treatment with the exception of the following Grade 2 toxicities: alopecia, peripheral neuropathy, any laboratory changes that still lie within the inclusion criteria defined above * History of other malignancy within 2 years; exception for ductal carcinoma in situ not requiring chemotherapy, low grade cervical intraepithelial neoplasia (CIN), nonmelanoma skin cancer, low grade localized prostate cancer (Gleason score \< Grade 7), or optimally treated Stage 1 uterine cancer. * Active or history of immunologic-mediated disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren's syndrome or Guillain-Barré syndrome * Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection. * Ascites, pleural effusion, or pericardial effusion requiring medical intervention within 12 months prior to study entry. * History of human immunodeficiency virus (HIV) infection * Active hepatitis B virus (HBV) infection * Coinfection of HBV and hepatitis C virus (HCV).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLT) | Baseline up to approximately 14 months | A DLT is defined as a clinically significant AE (classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v.5.0) or significant laboratory abnormality 1) occurring during an assessment period of 21 days or 28 days after first dose of study treatment, respectively, and 2) is not attributed to disease progression, concomitant illness or another clearly identifiable cause. |
| Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Baseline up to approximately 14 months | An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days) | — |
| Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days) | — |
| Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days) | — |
| Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days) | — |
| Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days) | — |
| Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days) | — |
| Progression-Free Survival (PFS) According to RECIST v1.1 | Baseline up to approximately 14 months | Progression-free survival (PFS) is defined as the time from randomization to disease progression or death from any cause. |
| Objective Response Rate (ORR) According to RECIST v1.1 | Baseline up to approximately 14 months | ORR is defined as the number of patients who achieve a response, which can either be complete response (complete disappearance of lesions) or partial response (reduction in the sum of maximal tumor diameters by at least 30% or more). |
| Overall Survival (OS) | Baseline up to approximately 14 months | Overall survival (OS) is defined as the time from randomization to death |
| Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days) | — |
| Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days) | — |
Countries
Denmark, Hong Kong, South Korea, Spain, Taiwan, United States
Participant flow
Pre-assignment details
At Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15, the participant were pre-medicated with 500 mL of crystalloid fluid and 500-1000 mg paracetamol orally (PO) or intravenously (IV) at the time of RO7119929 administration (± 30 minutes), followed by 500-1000 mg paracetamol PO or IV 4-6 hours after first drug administration. If no cytokine release syndrome (CRS) is observed, no further premedication was foreseen beyond Cycle 1.
Participants by arm
| Arm | Count |
|---|---|
| Part A1-1 mg RO7119929 Participants received 1mg RO7119929 every week in 3-week cycles. | 4 |
| Part A1-3 mg RO7119929 Participants received 3 mg RO7119929 every week in 3-week cycles. | 6 |
| Part A1 -4 mg RO7119929 Participants received 4 mg RO7119929 every week in 3-week cycles | 3 |
| Part A1 - 6 mg RO7119929 Participants received 6 mg RO7119929 every week in 3-week cycles | 10 |
| Part A1 -9 mg RO7119929 Participants received 9 mg RO7119929 every week in 3-week cycles | 4 |
| Part B1-5 mg RO7119929 Participants with both available and evaluable tumor biopsy samples received 5 mg RO7119929 on Cycle 1 Day 1 to month 12 | 18 |
| Part A2- 2/5/5 mg RO7119929 Participants received RO7119929 QW with step-up dosing of 2/5/5 mg during Cycle 1. | 4 |
| Part A2- 2/5/6 mg RO7119929 Participants received RO7119929 QW with step-up dosing of 2/5/6 mg during Cycle 1. | 5 |
| Part A3-4 mg RO7119929 Participants received tocilizumab pre-treatment on Cycle 1 Day 1, approximately 2 hours prior to RO7119929 administration and 4 mg RO7119929 every week in 3-week cycles | 1 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 4 | 2 | 4 | 4 | 8 | 1 | 0 | 0 |
| Overall Study | Study terminated by Sponsor | 0 | 0 | 1 | 4 | 0 | 5 | 2 | 4 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 | 2 | 0 | 5 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A1 -9 mg RO7119929 | Part B1-5 mg RO7119929 | Part A2- 2/5/5 mg RO7119929 | Part A2- 2/5/6 mg RO7119929 | Part A3-4 mg RO7119929 | Total | Part A1-1 mg RO7119929 | Part A1-3 mg RO7119929 | Part A1 -4 mg RO7119929 | Part A1 - 6 mg RO7119929 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 14 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 14 Participants | 3 Participants | 5 Participants | 1 Participants | 41 Participants | 3 Participants | 6 Participants | 1 Participants | 7 Participants |
| Age, Continuous | 62.8 Years STANDARD_DEVIATION 16 | 57.6 Years STANDARD_DEVIATION 9.8 | 55.3 Years STANDARD_DEVIATION 10.7 | 53.0 Years STANDARD_DEVIATION 10.3 | 68.0 Years | 58.1 Years STANDARD_DEVIATION 10.5 | 61.0 Years STANDARD_DEVIATION 5 | 57.5 Years STANDARD_DEVIATION 5 | 69.3 Years STANDARD_DEVIATION 10.8 | 55.9 Years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 18 Participants | 4 Participants | 5 Participants | 1 Participants | 55 Participants | 4 Participants | 6 Participants | 3 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 2 Participants | 3 Participants | 0 Participants | 28 Participants | 3 Participants | 4 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 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 | 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 | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 11 Participants | 2 Participants | 2 Participants | 1 Participants | 27 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 14 Participants | 0 Participants | 1 Participants | 0 Participants | 23 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 1 Participants | 32 Participants | 3 Participants | 5 Participants | 2 Participants | 5 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 4 / 6 | 2 / 3 | 4 / 10 | 4 / 4 | 8 / 18 | 1 / 4 | 0 / 5 | 0 / 1 |
| other Total, other adverse events | 3 / 4 | 6 / 6 | 3 / 3 | 10 / 10 | 3 / 4 | 18 / 18 | 4 / 4 | 5 / 5 | 1 / 1 |
| serious Total, serious adverse events | 1 / 4 | 2 / 6 | 2 / 3 | 4 / 10 | 4 / 4 | 11 / 18 | 1 / 4 | 2 / 5 | 0 / 1 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0
An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Baseline up to approximately 14 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A1-1 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Adverse Events | 3 Participants |
| Part A1-1 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Serious Adverse Events | 1 Participants |
| Part A1-3 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Adverse Events | 6 Participants |
| Part A1-3 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Serious Adverse Events | 2 Participants |
| Part A1 -4 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Adverse Events | 3 Participants |
| Part A1 -4 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Serious Adverse Events | 2 Participants |
| Part A1 - 6 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Adverse Events | 10 Participants |
| Part A1 - 6 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Serious Adverse Events | 4 Participants |
| Part A1 -9 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Adverse Events | 3 Participants |
| Part A1 -9 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Serious Adverse Events | 4 Participants |
| Part B1-5 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Serious Adverse Events | 11 Participants |
| Part B1-5 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Adverse Events | 18 Participants |
| Part A2- 2/5/5 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Serious Adverse Events | 1 Participants |
| Part A2- 2/5/5 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Adverse Events | 4 Participants |
| Part A2- 2/5/6 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Adverse Events | 5 Participants |
| Part A2- 2/5/6 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Serious Adverse Events | 2 Participants |
| Part A3-4 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Adverse Events | 1 Participants |
| Part A3-4 mg RO7119929 | Number of Participants With Adverse Events (AEs) According To NCI CTCAE v5.0 | Participants with Serious Adverse Events | 0 Participants |
Primary
Number of Participants With Dose-Limiting Toxicities (DLT)
A DLT is defined as a clinically significant AE (classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v.5.0) or significant laboratory abnormality 1) occurring during an assessment period of 21 days or 28 days after first dose of study treatment, respectively, and 2) is not attributed to disease progression, concomitant illness or another clearly identifiable cause.
Time frame: Baseline up to approximately 14 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A1-1 mg RO7119929 | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Part A1-3 mg RO7119929 | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Part A1 -4 mg RO7119929 | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Part A1 - 6 mg RO7119929 | Number of Participants With Dose-Limiting Toxicities (DLT) | 2 Participants |
| Part A1 -9 mg RO7119929 | Number of Participants With Dose-Limiting Toxicities (DLT) | 2 Participants |
| Part B1-5 mg RO7119929 | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Part A2- 2/5/5 mg RO7119929 | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Part A2- 2/5/6 mg RO7119929 | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Part A3-4 mg RO7119929 | Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
Secondary
Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929
Time frame: Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
Population: Participants in 9 mg cohort were excluded from the Cycle 2 analysis (2 discontinued the study due to DLTs, the other 2 were re-dosed at 3 mg)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A1-1 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 31.4 ng*hr/mL | Geometric Coefficient of Variation 50.7 |
| Part A1-1 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 39.9 ng*hr/mL | Geometric Coefficient of Variation 57.4 |
| Part A1-1 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 7.91 ng*hr/mL | Geometric Coefficient of Variation 43.5 |
| Part A1-1 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 6.27 ng*hr/mL | Geometric Coefficient of Variation 46 |
| Part A1-3 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 130 ng*hr/mL | Geometric Coefficient of Variation 42.9 |
| Part A1-3 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 4.94 ng*hr/mL | Geometric Coefficient of Variation 52.6 |
| Part A1-3 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 123 ng*hr/mL | Geometric Coefficient of Variation 41.6 |
| Part A1-3 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 6.08 ng*hr/mL | Geometric Coefficient of Variation 18.8 |
| Part A1 -4 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 164 ng*hr/mL | Geometric Coefficient of Variation 4.51 |
| Part A1 -4 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 3.52 ng*hr/mL | Geometric Coefficient of Variation 41 |
| Part A1 -4 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 155 ng*hr/mL | Geometric Coefficient of Variation 6.28 |
| Part A1 -4 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 4.79 ng*hr/mL | Geometric Coefficient of Variation 127 |
| Part A1 - 6 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 202 ng*hr/mL | Geometric Coefficient of Variation 56 |
| Part A1 - 6 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 6.55 ng*hr/mL | Geometric Coefficient of Variation 71.6 |
| Part A1 - 6 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 251 ng*hr/mL | Geometric Coefficient of Variation 69.9 |
| Part A1 - 6 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 6.82 ng*hr/mL | Geometric Coefficient of Variation 46.3 |
| Part A1 -9 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 8.93 ng*hr/mL | Geometric Coefficient of Variation 141 |
| Part A1 -9 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 314 ng*hr/mL | Geometric Coefficient of Variation 28.3 |
| Part B1-5 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 242 ng*hr/mL | Geometric Coefficient of Variation 32.8 |
| Part B1-5 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.17 ng*hr/mL | Geometric Coefficient of Variation 71.6 |
| Part B1-5 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 265 ng*hr/mL | Geometric Coefficient of Variation 48.9 |
| Part B1-5 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 10.8 ng*hr/mL | Geometric Coefficient of Variation 261 |
Secondary
Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose
Time frame: Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A1-1 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 1 Day 15 | 5.38 ng*hr/mL | Geometric Coefficient of Variation 89.6 |
| Part A1-1 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 2 Day 1 | 5.01 ng*hr/mL | Geometric Coefficient of Variation 73.9 |
| Part A1-1 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 1 Day 15 | 213 ng*hr/mL | Geometric Coefficient of Variation 31.1 |
| Part A1-1 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 2 Day 1 | 178 ng*hr/mL | Geometric Coefficient of Variation 24.1 |
| Part A1-3 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 2 Day 1 | 214 ng*hr/mL | Geometric Coefficient of Variation 21.4 |
| Part A1-3 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 1 Day 15 | 4.79 ng*hr/mL | Geometric Coefficient of Variation 134 |
| Part A1-3 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 1 Day 15 | 170 ng*hr/mL | Geometric Coefficient of Variation 23.5 |
| Part A1-3 mg RO7119929 | Area Under the Curve (AUC) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 2 Day 1 | 8.04 ng*hr/mL | Geometric Coefficient of Variation 167 |
Secondary
Half-Life (T1/2) for RO7119929 Following Administration of RO7119929
Time frame: Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
Population: Participants in 9 mg cohort were excluded from the Cycle 2 analysis (2 discontinued the study due to DLTs, the other 2 were re-dosed at 3 mg)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A1-1 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 0.896 hours | Geometric Coefficient of Variation 3.77 |
| Part A1-1 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 3.74 hours | Geometric Coefficient of Variation 37.6 |
| Part A1-1 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.45 hours | Geometric Coefficient of Variation 30.3 |
| Part A1-1 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 3.23 hours | Geometric Coefficient of Variation 48.8 |
| Part A1-3 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 4.93 hours | Geometric Coefficient of Variation 14.9 |
| Part A1-3 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 4.74 hours | Geometric Coefficient of Variation 24.9 |
| Part A1-3 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.54 hours | Geometric Coefficient of Variation 31.1 |
| Part A1-3 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.33 hours | Geometric Coefficient of Variation 37.7 |
| Part A1 -4 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 6.3 hours | Geometric Coefficient of Variation 26.1 |
| Part A1 -4 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.02 hours | Geometric Coefficient of Variation 22.7 |
| Part A1 -4 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 5.12 hours | Geometric Coefficient of Variation 16.9 |
| Part A1 -4 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.38 hours | Geometric Coefficient of Variation 75 |
| Part A1 - 6 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 5.00 hours | Geometric Coefficient of Variation 16.4 |
| Part A1 - 6 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.84 hours | Geometric Coefficient of Variation 58.3 |
| Part A1 - 6 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.55 hours | Geometric Coefficient of Variation 55.5 |
| Part A1 - 6 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 5.35 hours | Geometric Coefficient of Variation 43.8 |
| Part A1 -9 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 4.85 hours | Geometric Coefficient of Variation 14.2 |
| Part A1 -9 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 2.46 hours | Geometric Coefficient of Variation 65 |
| Part B1-5 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 3.89 hours | Geometric Coefficient of Variation 19 |
| Part B1-5 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.70 hours | Geometric Coefficient of Variation 35.3 |
| Part B1-5 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 4.86 hours | Geometric Coefficient of Variation 35.5 |
| Part B1-5 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.45 hours | Geometric Coefficient of Variation 61.8 |
Secondary
Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose
Time frame: Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A1-1 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 1 Day 15 | 1.49 hours | Geometric Coefficient of Variation 42.4 |
| Part A1-1 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 2 Day 1 | 1.40 hours | Geometric Coefficient of Variation 27.8 |
| Part A1-1 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 1 Day 15 | 5.11 hours | Geometric Coefficient of Variation 24.6 |
| Part A1-1 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 2 Day 1 | 5.62 hours | Geometric Coefficient of Variation 20.8 |
| Part A1-3 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 2 Day 1 | 6.11 hours | Geometric Coefficient of Variation 28.9 |
| Part A1-3 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 1 Day 15 | 1.56 hours | Geometric Coefficient of Variation 57.4 |
| Part A1-3 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 1 Day 15 | 5.84 hours | Geometric Coefficient of Variation 14.5 |
| Part A1-3 mg RO7119929 | Half-Life (T1/2) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 2 Day 1 | 1.53 hours | Geometric Coefficient of Variation 74.5 |
Secondary
Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929
Time frame: Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
Population: Participants in 9 mg cohort were excluded from the Cycle 2 analysis (2 discontinued the study due to DLTs, the other 2 were re-dosed at 3 mg)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A1-1 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 7.35 ng/m | Geometric Coefficient of Variation 37.4 |
| Part A1-1 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 7.28 ng/m | Geometric Coefficient of Variation 40.5 |
| Part A1-1 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.46 ng/m | Geometric Coefficient of Variation 231 |
| Part A1-1 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.29 ng/m | Geometric Coefficient of Variation 146 |
| Part A1-3 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 26.3 ng/m | Geometric Coefficient of Variation 52.8 |
| Part A1-3 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.94 ng/m | Geometric Coefficient of Variation 46.8 |
| Part A1-3 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 25.1 ng/m | Geometric Coefficient of Variation 49 |
| Part A1-3 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 2.49 ng/m | Geometric Coefficient of Variation 21.4 |
| Part A1 -4 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 39.7 ng/m | Geometric Coefficient of Variation 7.89 |
| Part A1 -4 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.85 ng/m | Geometric Coefficient of Variation 62.1 |
| Part A1 -4 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 30.7 ng/m | Geometric Coefficient of Variation 26.8 |
| Part A1 -4 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 2.01 ng/m | Geometric Coefficient of Variation 34.6 |
| Part A1 - 6 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 44.7 ng/m | Geometric Coefficient of Variation 92.7 |
| Part A1 - 6 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 2.34 ng/m | Geometric Coefficient of Variation 90.6 |
| Part A1 - 6 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 48.4 ng/m | Geometric Coefficient of Variation 64 |
| Part A1 - 6 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 2.77 ng/m | Geometric Coefficient of Variation 54.9 |
| Part A1 -9 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 3.67 ng/m | Geometric Coefficient of Variation 178 |
| Part A1 -9 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 60.9 ng/m | Geometric Coefficient of Variation 16.3 |
| Part B1-5 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 50.2 ng/m | Geometric Coefficient of Variation 32.7 |
| Part B1-5 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 3.18 ng/m | Geometric Coefficient of Variation 204 |
| Part B1-5 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 49.9 ng/m | Geometric Coefficient of Variation 40.2 |
| Part B1-5 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 4.30 ng/m | Geometric Coefficient of Variation 299 |
Secondary
Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose
Time frame: Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A1-1 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 2 Day 1 | 35.9 ng/mL | Geometric Coefficient of Variation 52.3 |
| Part A1-1 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 2 Day 1 | 2.37 ng/mL | Geometric Coefficient of Variation 48.9 |
| Part A1-1 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 1 Day 15 | 3.49 ng/mL | Geometric Coefficient of Variation 116 |
| Part A1-1 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 1 Day 15 | 41.1 ng/mL | Geometric Coefficient of Variation 54.9 |
| Part A1-3 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 1 Day 15 | 1.97 ng/mL | Geometric Coefficient of Variation 181 |
| Part A1-3 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 2 Day 1 | 44.4 ng/mL | Geometric Coefficient of Variation 32.7 |
| Part A1-3 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 1 Day 15 | 39.6 ng/mL | Geometric Coefficient of Variation 16.3 |
| Part A1-3 mg RO7119929 | Maximum Concentration (Cmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 2 Day 1 | 3.58 ng/mL | Geometric Coefficient of Variation 156 |
Secondary
Objective Response Rate (ORR) According to RECIST v1.1
ORR is defined as the number of patients who achieve a response, which can either be complete response (complete disappearance of lesions) or partial response (reduction in the sum of maximal tumor diameters by at least 30% or more).
Time frame: Baseline up to approximately 14 months
Population: Participants with missing tumor assessments and were not included in the efficacy analysis population for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A1-1 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Partial Response | 0 Participants |
| Part A1-1 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Complete Response | 0 Participants |
| Part A1-3 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Partial Response | 0 Participants |
| Part A1-3 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Complete Response | 0 Participants |
| Part A1 -4 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Partial Response | 0 Participants |
| Part A1 -4 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Complete Response | 0 Participants |
| Part A1 - 6 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Partial Response | 0 Participants |
| Part A1 - 6 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Complete Response | 1 Participants |
| Part A1 -9 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Complete Response | 0 Participants |
| Part A1 -9 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Partial Response | 0 Participants |
| Part B1-5 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Complete Response | 0 Participants |
| Part B1-5 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Partial Response | 0 Participants |
| Part A2- 2/5/5 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Partial Response | 0 Participants |
| Part A2- 2/5/5 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Complete Response | 0 Participants |
| Part A2- 2/5/6 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Complete Response | 0 Participants |
| Part A2- 2/5/6 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Partial Response | 0 Participants |
| Part A3-4 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Partial Response | 0 Participants |
| Part A3-4 mg RO7119929 | Objective Response Rate (ORR) According to RECIST v1.1 | Complete Response | 0 Participants |
Secondary
Overall Survival (OS)
Overall survival (OS) is defined as the time from randomization to death
Time frame: Baseline up to approximately 14 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A1-1 mg RO7119929 | Overall Survival (OS) | 3.2 Months |
| Part A1-3 mg RO7119929 | Overall Survival (OS) | 5.1 Months |
| Part A1 -4 mg RO7119929 | Overall Survival (OS) | 7.9 Months |
| Part A1 - 6 mg RO7119929 | Overall Survival (OS) | NA Months |
| Part A1 -9 mg RO7119929 | Overall Survival (OS) | 2.9 Months |
| Part B1-5 mg RO7119929 | Overall Survival (OS) | 8.0 Months |
| Part A2- 2/5/5 mg RO7119929 | Overall Survival (OS) | NA Months |
| Part A2- 2/5/6 mg RO7119929 | Overall Survival (OS) | NA Months |
| Part A3-4 mg RO7119929 | Overall Survival (OS) | NA Months |
Secondary
Progression-Free Survival (PFS) According to RECIST v1.1
Progression-free survival (PFS) is defined as the time from randomization to disease progression or death from any cause.
Time frame: Baseline up to approximately 14 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A1-1 mg RO7119929 | Progression-Free Survival (PFS) According to RECIST v1.1 | 1.2 Months |
| Part A1-3 mg RO7119929 | Progression-Free Survival (PFS) According to RECIST v1.1 | 1.4 Months |
| Part A1 -4 mg RO7119929 | Progression-Free Survival (PFS) According to RECIST v1.1 | 2.8 Months |
| Part A1 - 6 mg RO7119929 | Progression-Free Survival (PFS) According to RECIST v1.1 | 1.4 Months |
| Part A1 -9 mg RO7119929 | Progression-Free Survival (PFS) According to RECIST v1.1 | 1.2 Months |
| Part B1-5 mg RO7119929 | Progression-Free Survival (PFS) According to RECIST v1.1 | 1.6 Months |
| Part A2- 2/5/5 mg RO7119929 | Progression-Free Survival (PFS) According to RECIST v1.1 | 2.7 Months |
| Part A2- 2/5/6 mg RO7119929 | Progression-Free Survival (PFS) According to RECIST v1.1 | 2.8 Months |
| Part A3-4 mg RO7119929 | Progression-Free Survival (PFS) According to RECIST v1.1 | 3.9 Months |
Secondary
Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929
Time frame: Cycle 1, after 1st dose, Cycle 2, after 4th dose (Each cycle is 21 days)
Population: Participants in 9 mg cohort were excluded from the Cycle 2 analysis (2 discontinued the study due to DLTs, the other 2 were re-dosed at 3 mg)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A1-1 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 2.14 hour |
| Part A1-1 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 2.28 hour |
| Part A1-1 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.03 hour |
| Part A1-1 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.02 hour |
| Part A1-3 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 1.74 hour |
| Part A1-3 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.50 hour |
| Part A1-3 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 2.07 hour |
| Part A1-3 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 0.79 hour |
| Part A1 -4 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 1.52 hour |
| Part A1 -4 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.02 hour |
| Part A1 -4 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 1.53 hour |
| Part A1 -4 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.53 hour |
| Part A1 - 6 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 1.55 hour |
| Part A1 - 6 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.53 hour |
| Part A1 - 6 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 2.00 hour |
| Part A1 - 6 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.08 hour |
| Part A1 -9 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.28 hour |
| Part A1 -9 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 1.83 hour |
| Part B1-5 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Active Drug) | 2.17 hour |
| Part B1-5 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Prodrug) | 1.54 hour |
| Part B1-5 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 1, after 1st dose (Active Drug) | 3.01 hour |
| Part B1-5 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929 | Cycle 2, after 4th dose (Prodrug) | 1.17 hour |
Secondary
Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose
Time frame: Cycle 1 Day 15, Cycle 2 Day 1 (Cycle duration is 21 days)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A1-1 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 1 Day 15 | 0.51 hours |
| Part A1-1 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 2 Day 1 | 0.78 hours |
| Part A1-1 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 1 Day 15 | 1.03 hours |
| Part A1-1 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 2 Day 1 | 1.43 hours |
| Part A1-3 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 2 Day 1 | 2.35 hours |
| Part A1-3 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 1 Day 15 | 1.02 hours |
| Part A1-3 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Active Drug: Cycle 1 Day 15 | 1.98 hours |
| Part A1-3 mg RO7119929 | Time of Maximum Concentration Observed (Tmax) for RO7119929 Following Administration of RO7119929, Oral Step-Up Dose | Prodrug: Cycle 2 Day 1 | 2.35 hours |