Solid Tumors
Conditions
Brief summary
This study was to determine the maximum-tolerated dose (MTD) and/or the optimal biological dose (OBD) as well as the optimal schedule for intravenous (IV) and subcutaneous (SC) administrations of RO7172508 as monotherapy, with or without obinutuzumab pre-treatment, in participants with locally advanced and/or metastatic carcinoembryonic antigen (CEA)-positive solid tumors who have progressed on standard of care (SOC) treatment, are intolerant to SOC, and/or are non-amenable to SOC. This study was conducted in two parts. Part I of the study consisted of an IV single participant cohort/multiple-ascending dose-escalation to evaluate the safety of RO7172508. Part II was a multiple participant cohort/multiple-ascending dose-escalation to define the MTD and/or OBD of RO7172508 administered as single agent, IV and/or SC, in participants with tumors that are expressing high as well as moderate/low-CEA. The study switched from Part I to Part II when the maximum planned dose for Part I was reached or the occurrence of a RO7172508-related Grade \>= 2 adverse event (AE) or dose-limiting toxicity (DLT) was observed, whichever comes first. The Sponsor may decide to switch from Part I to Part II in the absence of an observed RO7172508-related Grade \>= 2 toxicity or prior to maximum planned dose for Part I.
Interventions
DRUGRO7172508
RO7172508 was administered at a dose and as per the schedule specified in the respective arms.
DRUGObinutuzumab
In the event obinutuzumab treatment is implemented, obinutuzumab will be administered either on Day-7 or on Day-7 and Day-6. If obinutuzumab is given only on one day, then the schedule for Day-7 should be followed including an end of infusion sample.
DRUGTocilizumab
Tocilizumab was administered if required, for the management of severe CRS (cytokine release syndrome)
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For Part I: participants with locally advanced and/or metastatic solid tumor with confirmed cytoplasmic and/or membranous high CEA expression in tumor tissue is required. Participants must have progressed on a SOC therapy, be intolerant to SOC, and/or are non-amenable to SOC. * For \<12 mg dose cohorts, serum CEA levels below a certain threshold is required as follows: * For dose cohorts 65-159 microgram, a sCEA level of \< 22 ng/mL * For dose cohorts 160-399 microgram, a sCEA level of \< 28 ng/mL * For dose cohorts 400-799 microgram, a sCEA level of \< 44 ng/mL * For dose cohorts 800-1599 microgram, a sCEA level of \< 70 ng/mL * For the dose cohort of 1.6-3.1 milligram, a sCEA level of \< 123 ng/mL * For the dose cohort of 3.2-6.3 milligram, an sCEA level of \< 229 ng/mL. * For the dose cohort of 6.4-11.9 milligram, an sCEA level of \< 440 ng/mL. If dose fractionation is implemented, the sCEA threshold for inclusion should correspond to the dose range of the first dose administered. * For Part II, participants with locally advanced and/or metastatic solid tumor expressing cytoplasmic and/or membranous high-CEA or moderate/low-CEA on archival material, who have progressed on a SOC therapy, are intolerant to SOC, and/or are non-amenable to SOC. Participants must have a lesion amenable to biopsy (except participants with NSCLC, which may be enrolled with archival tissue available only). For participants with colorectal cancer (CRC) only, the CEA assessment by immunohistochemistry should be performed but the result is not required to enroll the participant. * Radiologically measurable disease according to RECIST v1.1. * Life expectancy of \>= 12 weeks * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1. * All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade \<= 1 or returned to baseline except alopecia (any grade) and Grade 2 peripheral neuropathy. * Adequate hematological, liver, renal, and lung function * For women: agree to remain abstinent or use two contraceptive methods that result in a failure rate of \<1% per year from screening until 2 months after the last dose of RO7172508 and have a negative pregnancy test within one week prior to the first study treatment administration * For men: remain abstinent or use contraceptive measures such as a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year, with partners who are woman of childbearing potential and refrain from donating sperm during the study
Exclusion criteria
* History or clinical evidence of central nervous system (CNS) primary tumors or 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 before screening. * Non-irradiated lesions \> 2 cm at critical sites where tumor swelling induced by RO7172508 is expected to lead to significant complications. * Another invasive malignancy in the last 2 years * Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or contraindicate the use of an investigational drug. * Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia that requires treatment with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia, and history of myocardial infarction within 6 months of enrollment. * Active or uncontrolled infections. * Known hepatitis B or C * Major surgery or significant traumatic injury \< 28 days prior to the first RO7172508 administration or anticipation of the need for major surgery during study treatment. Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Up to approximately 12 months | Number of participants with DLTs. |
| Percentage of Participants With Adverse Events | 60 days after last dose of study treatment (up to approximately 12 months) | Percentage of participants with adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clearance or Apparent Clearance of RO7172508 | Cycle 1 following single dose administration of RO7172508 | — |
| Volume of Distribution at Steady State of RO7172508 | Cycle 1 following single dose administration of RO7172508 | — |
| Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Cycle 1 following single dose administration of RO7172508 | — |
| Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Cycle 1 following single dose administration of RO7172508 | — |
| Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Cycle 1 following single dose administration of RO7172508 | — |
| Half-Life of RO7172508 | Cycle 1 following single dose administration of RO7172508 | — |
| Presence or Absence and Titer of ADAs | Up to approximately 12 months | — |
| Maximum Concentration of RO7172508 | Cycle 1 following single dose administration of RO7172508 | — |
| Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days) | — |
| Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days) | — |
| Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days) | Spatial distribution of TIL's analyzed by performing IHC assay, which measures the density and intra-tumoral location of CD8+ T cells and reports CD8 T cell immune phenotypes. These are classified as desert, excluded and inflamed. |
| Objective Response Rate (ORR) | Up to approximately 12 months | Objective response was defined as a Complete Response (CR) or Parital Response (PR), as determined by the Investigator's assessment using RECIST v1.1 and confirmed by repeat assessments \>= 4 weeks after initial documentation. To classify a response as SD, measurements are classified as stable (according to RECIST v1.1) at least once after study entry at a minimum of 6 weeks after study entry. |
| Disease Control Rate (DCR) | Up to approximately 12 months | DCR is determined as the rate of participants with an observed tumor response of CR or PR (ORR) or CR, PR or SD (DCR). DCR is to be derived for RECIST v1.1. |
| Duration of Response (DOR) | Up to approximately 12 month | Among participants with an objective response (responders), DOR will be defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death within 30 days from last study treatment from any cause during treatment, whichever occurs first. This will be calculated for participants who have a best overall response of CR or PR as defined per RECIST v1.1 and per iRECIST. |
| Progression Free Survival (PFS) | Up to approxmately 12 months | PFS (on-treatment) will be defined as the time from study treatment initiation (Cycle 1 Day 1) to the first occurrence of documented disease progression or death from any cause during treatment (death within 30 days from last study treatment), whichever occurs first. |
| Changes in Frequency of Tumor Infiltrating Lymphocytes | Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days) | — |
| Time of Maximum Concentration of RO7172508 | Cycle 1 following single dose administration of RO7172508 | — |
Countries
Belgium, Canada, Denmark, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PART1 - RO7172508 - Q3W - 65 mcg Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 65 microgram (mcg). | 1 |
| PART1 - RO7172508 - Q3W - 160 mcg Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 160 microgram (mcg). | 1 |
| PART1 - RO7172508 - Q3W - 400 mcg Part I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W) at a dose of 400 microgram (mcg). | 1 |
| PART2 - RO7172508 - Q3W - 400 mcg Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Starting dose of RO7172508 was 400 mcg. | 3 |
| PART2 - RO7172508 - Q3W - 800 mcg Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 800 mcg. | 13 |
| PART2 - RO7172508 - Q3W - 1200 mcg Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1200 mcg. | 5 |
| PART2 - RO7172508 - Q3W - 1800 mcg Part II was a multiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts. RO7172508 was administered intravenously at a dose of 1800 mcg. | 2 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 | 2 | 8 | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Study Terminated by Sponsor | 0 | 0 | 1 | 1 | 2 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | PART1 - RO7172508 - Q3W - 65 mcg | PART1 - RO7172508 - Q3W - 160 mcg | PART1 - RO7172508 - Q3W - 400 mcg | PART2 - RO7172508 - Q3W - 400 mcg | PART2 - RO7172508 - Q3W - 800 mcg | PART2 - RO7172508 - Q3W - 1200 mcg | PART2 - RO7172508 - Q3W - 1800 mcg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.0 Years | 60.0 Years | 60.0 Years | 53.7 Years STANDARD_DEVIATION 9.6 | 62.2 Years STANDARD_DEVIATION 9 | 58.8 Years STANDARD_DEVIATION 13.5 | 55.5 Years STANDARD_DEVIATION 16.3 | 59.5 Years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 13 Participants | 5 Participants | 2 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 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 |
| 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 13 Participants | 5 Participants | 2 Participants | 26 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 7 Participants | 4 Participants | 2 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 6 Participants | 1 Participants | 0 Participants | 12 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 0 / 1 | 0 / 1 | 2 / 3 | 8 / 13 | 3 / 5 | 0 / 2 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 3 / 3 | 13 / 13 | 5 / 5 | 2 / 2 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 | 1 / 1 | 0 / 3 | 8 / 13 | 3 / 5 | 2 / 2 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
Number of participants with DLTs.
Time frame: Up to approximately 12 months
Population: DLT evaluble population included participants who completed the DLT window without a DLT, or participants who reported with a DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part II: Multiple Participant Cohorts IV 400 mcg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part II: Multiple Participant Cohorts IV 800 mcg | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part II: Multiple Participant Cohorts IV 1800 mcg | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
95% CI: [2.1, 26.5]Regression, Logistic
Primary
Percentage of Participants With Adverse Events
Percentage of participants with adverse events.
Time frame: 60 days after last dose of study treatment (up to approximately 12 months)
Population: Safety population included all participants enrolled in the study who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Percentage of Participants With Adverse Events | 100 Percentage of participants |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Percentage of Participants With Adverse Events | 100 Percentage of participants |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Percentage of Participants With Adverse Events | 100 Percentage of participants |
| Part II: Multiple Participant Cohorts IV 400 mcg | Percentage of Participants With Adverse Events | 100 Percentage of participants |
| Part II: Multiple Participant Cohorts IV 800 mcg | Percentage of Participants With Adverse Events | 100 Percentage of participants |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Percentage of Participants With Adverse Events | 100 Percentage of participants |
| Part II: Multiple Participant Cohorts IV 1800 mcg | Percentage of Participants With Adverse Events | 100 Percentage of participants |
Secondary
Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA <=20 ng/mL | 6.93 day*ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA <=20 ng/mL | 1.91 day*ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA >20 ng/mL | 45.4 day*ng/mL | Geometric Coefficient of Variation 34.4 |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA <=20 ng/mL | 143 day*ng/mL | Geometric Coefficient of Variation 38.4 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA >20 ng/mL | 83.5 day*ng/mL | Geometric Coefficient of Variation 178 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA <=20 ng/mL | 411 day*ng/mL | Geometric Coefficient of Variation 137 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA <=20 ng/mL | 740 day*ng/mL | Geometric Coefficient of Variation 49.4 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA >20 ng/mL | 370 day*ng/mL | Geometric Coefficient of Variation 121 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA >20 ng/mL | 1910 day*ng/mL | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508 | Baseline sCEA <=20 ng/mL | 2140 day*ng/mL | — |
Secondary
Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA <=20 ng/mL | 8.15 day*ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA <=20 ng/mL | NA day*ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA >20 ng/mL | 36.8 day*ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA <=20 ng/mL | 150 day*ng/mL | Geometric Coefficient of Variation 34.7 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA >20 ng/mL | 98.1 day*ng/mL | Geometric Coefficient of Variation 527 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA <=20 ng/mL | 602 day*ng/mL | Geometric Coefficient of Variation 61.7 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA <=20 ng/mL | 740 day*ng/mL | Geometric Coefficient of Variation 49.2 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA >20 ng/mL | 727 day*ng/mL | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA >20 ng/mL | 1910 day*ng/mL | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508 | Baseline sCEA <=20 ng/mL | 2160 day*ng/mL | — |
Secondary
Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4)
Time frame: Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)
Population: Biopsies were not mandatory in part 1. Results from 2 participants are excluded as measured using a different assay.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD279+ Pre-treatment (Cycle 1 Day 1) | 16.50 % of CD4 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD279+ On-treatment (Cycle 2 Day 8) | 27.40 % of CD4 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD25+ Pre-treatment (Cycle 1 Day 1) | 51.9 % of CD4 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD25+ On-treatment (Cycle 2 Day 8) | 47.35 % of CD4 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD279+ Pre-treatment (Cycle 1 Day 1) | 10.90 % of CD4 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD25+ On-treatment (Cycle 2 Day 8) | 47.65 % of CD4 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD279+ On-treatment (Cycle 2 Day 8) | 24.30 % of CD4 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD25+ Pre-treatment (Cycle 1 Day 1) | 41.20 % of CD4 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD279+ On-treatment (Cycle 2 Day 8) | 22.40 % of CD4 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD25+ Pre-treatment (Cycle 1 Day 1) | 26.90 % of CD4 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD25+ On-treatment (Cycle 2 Day 8) | 30.75 % of CD4 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4) | CD4+CD279+ Pre-treatment (Cycle 1 Day 1) | 16.80 % of CD4 |
Secondary
Changes in Frequency of Tumor Infiltrating Lymphocytes
Time frame: Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)
Population: Biopsies were not mandatory in part 1. Results from 2 participants are excluded as measured using a different assay.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD8 TIL Pre-treatment (Cycle 1 Day 1) | 48.2 % of CD3 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD8 TIL On-treatment (Cycle 2 Day 8) | 54.15 % of CD3 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD4 TIL Pre-treatment (Cycle 1 Day 1) | 39.7 % of CD3 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD4 TIL On-treatment (Cycle 2 Day 8) | 35.00 % of CD3 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD4 TIL On-treatment (Cycle 2 Day 8) | 33.80 % of CD3 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD8 TIL Pre-treatment (Cycle 1 Day 1) | 41.40 % of CD3 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD4 TIL Pre-treatment (Cycle 1 Day 1) | 35.70 % of CD3 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD8 TIL On-treatment (Cycle 2 Day 8) | 54.7 % of CD3 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD4 TIL On-treatment (Cycle 2 Day 8) | 42.65 % of CD3 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD8 TIL On-treatment (Cycle 2 Day 8) | 52.75 % of CD3 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD4 TIL Pre-treatment (Cycle 1 Day 1) | 22.90 % of CD3 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Frequency of Tumor Infiltrating Lymphocytes | CD8 TIL Pre-treatment (Cycle 1 Day 1) | 64.4 % of CD3 |
Secondary
Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes
Spatial distribution of TIL's analyzed by performing IHC assay, which measures the density and intra-tumoral location of CD8+ T cells and reports CD8 T cell immune phenotypes. These are classified as desert, excluded and inflamed.
Time frame: Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)
Population: Paired included participant's with different dose and actual exposure levels. Data were pooled across all dose levels because the number of biopsy evaluable participants was overall small, and no dose/response relationship was found.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | On-treatment (Cycle 2 Day 8) Desert | 2 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Excluded | 0 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | On-treatment (Cycle 2 Day 8) Excluded | 0 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Inflamed | 0 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Desert | 1 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 400 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | On-treatment (Cycle 2 Day 8) Inflamed | 0 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Desert | 5 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | On-treatment (Cycle 2 Day 8) Desert | 6 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | On-treatment (Cycle 2 Day 8) Inflamed | 2 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Inflamed | 2 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | On-treatment (Cycle 2 Day 8) Excluded | 1 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 800 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Excluded | 0 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | On-treatment (Cycle 2 Day 8) Inflamed | 1 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Desert | 0 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Excluded | 1 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Inflamed | 1 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | On-treatment (Cycle 2 Day 8) Desert | 1 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | On-treatment (Cycle 2 Day 8) Excluded | 2 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 1800 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Inflamed | 1 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 1800 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Excluded | 1 CD8 immune phenotype |
| Part II: Multiple Participant Cohorts IV 1800 mcg | Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes | Pre-treatment (Cycle 1 Day 1) Desert | 0 CD8 immune phenotype |
Secondary
Clearance or Apparent Clearance of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA <=20 ng/mL | 332 mL/hr | — |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA <=20 ng/mL | NA mL/hr | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA >20 ng/mL | 453 mL/hr | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA <=20 ng/mL | 111 mL/hr | Geometric Coefficient of Variation 34.4 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA >20 ng/mL | 340 mL/hr | Geometric Coefficient of Variation 527 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA <=20 ng/mL | 55.4 mL/hr | Geometric Coefficient of Variation 61.5 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA <=20 ng/mL | 67.4 mL/hr | Geometric Coefficient of Variation 49.2 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA >20 ng/mL | 68.8 mL/hr | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA >20 ng/mL | 39.3 mL/hr | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Clearance or Apparent Clearance of RO7172508 | Baseline sCEA <=20 ng/mL | 34.8 mL/hr | — |
Secondary
Disease Control Rate (DCR)
DCR is determined as the rate of participants with an observed tumor response of CR or PR (ORR) or CR, PR or SD (DCR). DCR is to be derived for RECIST v1.1.
Time frame: Up to approximately 12 months
Population: Efficacy population included all participants who received at least one dose of RO7172508.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Disease Control Rate (DCR) | 0 Participants |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Disease Control Rate (DCR) | 0 Participants |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Disease Control Rate (DCR) | 0 Participants |
| Part II: Multiple Participant Cohorts IV 400 mcg | Disease Control Rate (DCR) | 1 Participants |
| Part II: Multiple Participant Cohorts IV 800 mcg | Disease Control Rate (DCR) | 3 Participants |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Disease Control Rate (DCR) | 1 Participants |
| Part II: Multiple Participant Cohorts IV 1800 mcg | Disease Control Rate (DCR) | 0 Participants |
Secondary
Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA <=20 ng/mL | 125 day*ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA <=20 ng/mL | NA day*ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA >20 ng/mL | 92.0 day*ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA <=20 ng/mL | 375 day*ng/mL | Geometric Coefficient of Variation 34.2 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA >20 ng/mL | 122 day*ng/mL | Geometric Coefficient of Variation 526 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA <=20 ng/mL | 753 day*ng/mL | Geometric Coefficient of Variation 61.6 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA <=20 ng/mL | 618 day*ng/mL | Geometric Coefficient of Variation 49.3 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA >20 ng/mL | 606 day*ng/mL | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA >20 ng/mL | 1060 day*ng/mL | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508 | Baseline sCEA <=20 ng/mL | 1200 day*ng/mL | — |
Secondary
Duration of Response (DOR)
Among participants with an objective response (responders), DOR will be defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death within 30 days from last study treatment from any cause during treatment, whichever occurs first. This will be calculated for participants who have a best overall response of CR or PR as defined per RECIST v1.1 and per iRECIST.
Time frame: Up to approximately 12 month
Population: Efficacy population included all participants who received at least one dose of RO7172508. DOR was not calculated because none of the participants had a response (complete or partial).
Secondary
Half-Life of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Half-Life of RO7172508 | Baseline sCEA <=20 ng/mL | 17.1 Hour | — |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Half-Life of RO7172508 | Baseline sCEA <=20 ng/mL | NA Hour | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Half-Life of RO7172508 | Baseline sCEA >20 ng/mL | 9.27 Hour | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Half-Life of RO7172508 | Baseline sCEA <=20 ng/mL | 54.0 Hour | Geometric Coefficient of Variation 112 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Half-Life of RO7172508 | Baseline sCEA >20 ng/mL | 22.0 Hour | Geometric Coefficient of Variation 43.9 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Half-Life of RO7172508 | Baseline sCEA <=20 ng/mL | 62.1 Hour | Geometric Coefficient of Variation 42.4 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Half-Life of RO7172508 | Baseline sCEA <=20 ng/mL | 40.9 Hour | Geometric Coefficient of Variation 68.9 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Half-Life of RO7172508 | Baseline sCEA >20 ng/mL | 23.3 Hour | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Half-Life of RO7172508 | Baseline sCEA >20 ng/mL | 18.4 Hour | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Half-Life of RO7172508 | Baseline sCEA <=20 ng/mL | 48.7 Hour | — |
Secondary
Maximum Concentration of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 9.19 ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 21.5 ng/mL | — |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Maximum Concentration of RO7172508 | Baseline sCEA >20 ng/mL | 85.0 ng/mL | Geometric Coefficient of Variation 17.3 |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 73.3 ng/mL | Geometric Coefficient of Variation 54.4 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Maximum Concentration of RO7172508 | Baseline sCEA >20 ng/mL | 184 ng/mL | Geometric Coefficient of Variation 167 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 252 ng/mL | Geometric Coefficient of Variation 138 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 370 ng/mL | Geometric Coefficient of Variation 29.2 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Maximum Concentration of RO7172508 | Baseline sCEA >20 ng/mL | 290 ng/mL | Geometric Coefficient of Variation 2.9 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Maximum Concentration of RO7172508 | Baseline sCEA >20 ng/mL | 1180 ng/mL | — |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 937 ng/mL | — |
Secondary
Objective Response Rate (ORR)
Objective response was defined as a Complete Response (CR) or Parital Response (PR), as determined by the Investigator's assessment using RECIST v1.1 and confirmed by repeat assessments \>= 4 weeks after initial documentation. To classify a response as SD, measurements are classified as stable (according to RECIST v1.1) at least once after study entry at a minimum of 6 weeks after study entry.
Time frame: Up to approximately 12 months
Population: Efficacy population included all participants who received at least one dose of RO7172508.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Objective Response Rate (ORR) | 0 Participants |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Objective Response Rate (ORR) | 0 Participants |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Objective Response Rate (ORR) | 0 Participants |
| Part II: Multiple Participant Cohorts IV 400 mcg | Objective Response Rate (ORR) | 0 Participants |
| Part II: Multiple Participant Cohorts IV 800 mcg | Objective Response Rate (ORR) | 0 Participants |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Objective Response Rate (ORR) | 0 Participants |
| Part II: Multiple Participant Cohorts IV 1800 mcg | Objective Response Rate (ORR) | 0 Participants |
Secondary
Presence or Absence and Titer of ADAs
Time frame: Up to approximately 12 months
Population: Participants were considered as evaluable for immunogenicity analysis if they had at least 3 cycles of treatment to allow for development of potential ADAs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Presence or Absence and Titer of ADAs | Presence of ADAs | 0 Participants |
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Presence or Absence and Titer of ADAs | Positive Titer | 0 Participants |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Presence or Absence and Titer of ADAs | Presence of ADAs | 0 Participants |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Presence or Absence and Titer of ADAs | Positive Titer | 0 Participants |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Presence or Absence and Titer of ADAs | Presence of ADAs | 1 Participants |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Presence or Absence and Titer of ADAs | Positive Titer | 1 Participants |
| Part II: Multiple Participant Cohorts IV 400 mcg | Presence or Absence and Titer of ADAs | Presence of ADAs | 3 Participants |
| Part II: Multiple Participant Cohorts IV 400 mcg | Presence or Absence and Titer of ADAs | Positive Titer | 3 Participants |
| Part II: Multiple Participant Cohorts IV 800 mcg | Presence or Absence and Titer of ADAs | Presence of ADAs | 5 Participants |
| Part II: Multiple Participant Cohorts IV 800 mcg | Presence or Absence and Titer of ADAs | Positive Titer | 5 Participants |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Presence or Absence and Titer of ADAs | Presence of ADAs | 2 Participants |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Presence or Absence and Titer of ADAs | Positive Titer | 2 Participants |
| Part II: Multiple Participant Cohorts IV 1800 mcg | Presence or Absence and Titer of ADAs | Presence of ADAs | 0 Participants |
| Part II: Multiple Participant Cohorts IV 1800 mcg | Presence or Absence and Titer of ADAs | Positive Titer | 0 Participants |
Secondary
Progression Free Survival (PFS)
PFS (on-treatment) will be defined as the time from study treatment initiation (Cycle 1 Day 1) to the first occurrence of documented disease progression or death from any cause during treatment (death within 30 days from last study treatment), whichever occurs first.
Time frame: Up to approxmately 12 months
Population: Efficacy population included all participants who received at least one dose of RO7172508. PFS was not calculated because number of evaluable participants in each cohort respectively was too small to obtain reliable estimates for this endpoint.
Secondary
Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8)
Time frame: Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)
Population: Biopsies were not mandatory in part 1. Results from 2 participants are excluded as measured using a different assay.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part II: Multiple Participant Cohorts IV 400 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD25+ Pre-treatment (Cycle 1 Day 1) | 22.00 % of CD8 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD25+ On-treatment (Cycle 2 Day 8) | 25.80 % of CD8 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD279+ Pre-treatment (Cycle 1 Day 1) | 11.90 % of CD8 |
| Part II: Multiple Participant Cohorts IV 400 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD279+ On-treatment (Cycle 2 Day 8) | 16.80 % of CD8 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD279+ On-treatment (Cycle 2 Day 8) | 23.20 % of CD8 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD25+ Pre-treatment (Cycle 1 Day 1) | 17.60 % of CD8 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD279+ Pre-treatment (Cycle 1 Day 1) | 8.70 % of CD8 |
| Part II: Multiple Participant Cohorts IV 800 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD25+ On-treatment (Cycle 2 Day 8) | 35.30 % of CD8 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD279+ On-treatment (Cycle 2 Day 8) | 7.90 % of CD8 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD25+ On-treatment (Cycle 2 Day 8) | 19.60 % of CD8 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD279+ Pre-treatment (Cycle 1 Day 1) | 11.40 % of CD8 |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8) | CD8+CD25+ Pre-treatment (Cycle 1 Day 1) | 9.70 % of CD8 |
Secondary
Time of Maximum Concentration of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part I: Single Participant Cohort IV RO7172508 65 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 2.58 Hour |
| Part I: Single Participant Cohort IV RO7172508 160 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 2.07 Hour |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA >20 ng/mL | 2.16 Hour |
| Part I: Single Participant Cohort IV RO7172508 400 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 3.30 Hour |
| Part II: Multiple Participant Cohorts IV 400 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA >20 ng/mL | 2.18 Hour |
| Part II: Multiple Participant Cohorts IV 400 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 3.79 Hour |
| Part II: Multiple Participant Cohorts IV 800 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 2.13 Hour |
| Part II: Multiple Participant Cohorts IV 800 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA >20 ng/mL | 3.09 Hour |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA >20 ng/mL | 1.95 Hour |
| Part II: Multiple Participant Cohorts IV 1200 mcg | Time of Maximum Concentration of RO7172508 | Baseline sCEA <=20 ng/mL | 4.48 Hour |
Secondary
Volume of Distribution at Steady State of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
Population: Analysis not conducted due to participants not reaching steady state due to early withdrawal or loss of exposure due to immunogenicity.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Volume of Distribution at Steady State of RO7172508 | Baseline sCEA <=20 ng/mL | — |
| Unknown | Volume of Distribution at Steady State of RO7172508 | Baseline sCEA >20 ng/mL | — |