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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
RO7172508 was administered at a dose and as per the schedule specified in the respective arms.
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.
Tocilizumab was administered if required, for the management of severe CRS (cytokine release syndrome)
Cliniques Universitaires St-Luc
Brussels, Belgium
Princess Margaret Cancer Center
Toronto, Ontario, Canada
Rigshospitalet; Onkologisk Klinik
København Ø, Denmark
Clinica Universitaria de Navarra
Pamplona, Navarre, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Spain
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Madrid, Spain
Number of Participants With Dose Limiting Toxicities (DLTs)
Number of participants with DLTs.
Time frame: Up to approximately 12 months
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)
Maximum Concentration of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
Time of Maximum Concentration of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
Clearance or Apparent Clearance of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
Volume of Distribution at Steady State of RO7172508
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Cycle 1 following single dose administration of RO7172508
Half-Life of RO7172508
Time frame: Cycle 1 following single dose administration of RO7172508
Presence or Absence and Titer of ADAs
Time frame: Up to approximately 12 months
Changes in Frequency of Tumor Infiltrating Lymphocytes
Time frame: Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)
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)
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)
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)
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
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
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
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
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