Neoplasms

All Conditions

Digestive System Diseases

Adenocarcinoma

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Obinutuzumab

Antineoplastic Agents, Immunological

The dose-escalation of RO7122290 will use a QW dosing schedule of RO7122290 in combination with a Q3W dosing interval for cibisatamab with obinutuzumab pre-treatment. The starting dose for RO7122290 will be 35 mg, which represents the human equivalent dose for the minimal pharmacologically active dose (1 mg/kg) in mice.

Part II of this study will evaluate selected dose levels of RO7122290 from Part I (a QW RO712290 administration in combination with a Q3W cibisatamab administration with obinutuzumab pre-treatment) in a Q3W regimen in combination with a Q3W cibisatamab administration with obinutuzumab pre-treatment.

RO7122290 will be administered using a QW (Part I) or Q3W (Part I or Part II) schedule in combination with 100 mg cibisatamab Q3W with obinutuzumab pre-treatment. The maximum dose of RO7122290 to be explored in combination with cibisatamab with obinutuzumab pre-treatment in this study is 500 mg for the QW dosing interval (Part I) or 1500 mg for the Q3W dosing interval (Part I or Part II).

RO7122290

Cibisatamab will be administered to participants at a fixed dose of 100 mg Q3W (100 mg on Day 1 of each 21-day cycle).

Cibisatamab

Obinutuzumab will be administered (IV) as pre-treatment on Day - 8/- 7 (split dose) or

- 8 (single dose) prior to C1D1 of cibisatamab and as re-treatment every 6 months if the participant is still receiving cibisatamab

Clinical Trials

This is an open-label, multicenter, Phase Ib study to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) in the weekly (QW) and/or every 3 weeks (Q3W) regimens, safety, tolerability, PK, immunogenicity, PD profile and to evaluate preliminary anti-tumor activity of RO7122290 in combination with cibisatamab Q3W after pretreatment with obinutuzumab, in participants with previously treated metastatic, microsatellite-stable colorectal adenocarcinoma with high CEACAM5 expression

Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290 In Combination With Cibisatamab With Obinutuzumab Pre-Treatment

An Open-Label, Multicenter, Phase Ib Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290, A Fibroblast Activation Protein-A (FAP) Targeted 4-1BB Ligand (CD137L), In Combination With Cibisatamab With Obinutuzumab Pre-Treatment, In Participants With Previously Treated, Metastatic, Microsatellite-stable Colorectal Adenocarcinoma With High CEACAM5 Expression

The DLT observation period is defined as a period of 21 days after the first administration of RO7122290 combined with cibisatamab. Additional days (maximum 3 days per dosing) are allowed in case of treatment delays for non-safety reasons.

Participants are evaluable for DLT assessment, if they have received one dose of cibisatamab and at least two doses of RO7122290 during the DLT period.

Incidence, nature, and severity of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 with the exception of cytokine release syndrome (CRS), which is graded according to the ASTCT grading scale for CRS (with individual signs and symptoms of CRS graded separately using the CTCAE v5.0 grading scale)

Part I:

Cycle 1: Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); Day 4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose), D9 (24h postdose); D12 (96h postdose); D15 (Predose, 15 minutes, 4h postdose); D16 (24h postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); D2 (24h postdose), D8 (Predose, 15 minutes, 4h postdose); D9 (24h postdose); D15 (Predose, 15 minutes postdose); Subsequent Cycles D1 (Predose, 15 minutes postdose); D8 (Predose, 15 minutes postdose); D15 ((Predose, 15 minutes postdose); Discontinuation visit; 28 Day Safety Follow Up Visit, 90 (±7 days) post last dose after last dose of RO7122290.

Part II:

Cycle 1 Day 1 (Predose, 15minutes 4h, 8h, postdose); Day 2; D4; D8; D9; D12 ; D15; Cycle 2, Day 1 (Predose, 15 minutes postdose); Day 2; D8; D9; D12; Subsequent Cycles Day 1 (Predose, 15 minutes postdose) D8; D16; Discontinuation visit; 28 Day Follow Up; Safety FU Visit. Each cycle is 21 days

Part I:

Cycle 1 Day 1 (Predose, 15 minutes, 4h, 8h postdose); Day 2 (24h postdose); D4 (72h postdose); D8 (Predose, 15 minutes, 4h postdose); D15 (Predose); Cycle 2 Day 1 (Predose), Discontinuation visit

Part II:

Cycle 1 Day 1 (Predose, 15 minutes, 4h postdose); Day 2 (24h postdose); D8 (Predose, 15 minutes, 4h postdose); Cycle 2 Day 1 (Predose, 15 min, 4h postdose,); Day 2 (24h postdose); D8 (168h postdose); C3-16 D1, then every 4th cycle (Predose); Discontinuation visit. Each cycle is 21 days

Obinutuzumab pretreatment: D -13 (Predose, 15 minutes postdose); D -12 (only in case of split dosing, done on D-13 and D-12: (Predose, 15 minutes postdose); D8 (Predose); Subsequent Cycles (Predose); Discontinuation visit. Each cycle is 21 days

Cycle 1: Day 1, 8, 15; Cycles 3, 4, 6, 8: Day 1; Discontinuation visit. Each cycle is 21 days

Cycle 1 Day 1 (Predose, 15 minutes postdose); Cycle 2 Day 1 (Predose, 15 minutes postdose); Day 8 (Predose); C3-16 D1, then every 4th cycle; Discontinuation visit. Each cycle is 21 days

Obinutuzumab pretreatment: Day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); C3, 4, 6, 8 Day 1; Discontinuation visit. Each cycle is 21 days

Obinutuzumab pretreatment: day -13, Day -12 (only in case of split dosing, done on D-13 and D-12); Cycle 1, Day 1;4, 8, 9, 12, 15, 16; Cycle 2, Day 1, 2, 8, 9, 12, 15; C3-12 D1, then every 4th cycle; Discontinuation visit; 28 Day Safety Follow Up; 90 (±7 days) post last dose after last dose of RO7122290 or cibisatamab 180 (+30) days after last dose. Each cycle is 21 days

Objective response rate (ORR) is determined as the rate of participants with an objective tumor response of CR or PR. ORR will be derived for RECIST Version 1.1 and will be based on Investigators' assessment.

Disease control rate (DCR) is determined as the rate of participants with an objective tumor response of CR, PR or SD. DCR will be derived for RECIST Version 1.1 and will be based on Investigators' assessment.

DoR will be calculated for participants who have a best overall response of CR or PR and will be defined as the time from first occurrence of a documented OR until the time of documented disease progression or death (death within 30 days from last study treatment) from any cause, whichever occurs first. Censoring

PFS will be defined as the time from first dose of cibisatamab or RO7122290 (C1D1) to the first occurrence of documented disease progression (based on RECIST Version 1.1 Investigator's assessment) or death from any cause, whichever occurs first. For participants who do not have documented progressive disease or death (within 30 days from last study treatment) during the study, PFS will be censored at the day of the last tumor assessment. Participants without any post-baseline assessments or with all post-baseline assessments having unknown result/response but known to be alive at the clinical cut off for the analysis will be censored at the date of study treatment initiation plus one day.

Mandatory for the 4th-12th participant of each dose level

Spots Global Cancer Trial Database for Study To Evaluate Safety, Pharmacokinetics, Pharmacodynamics, And Preliminary Anti-Tumor Activity Of RO7122290 In Combination With Cibisatamab With Obinutuzumab Pre-Treatment

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial