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

NCT04826003 | Completed Phase 1

• 1 other identifier: BP42675
• Study Type: interventional
• Target: 54
• Locations: 5 countries
• Sites: 13

Brief Summary

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

Conditions

Metastatic Colorectal Cancer

Keywords

Microsatellite stable;; Metastatic colorectal cancer

Outcome Measures

Primary Outcomes (2)

• Part I: Occurrence of dose-limiting toxicities

  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.

  Baseline up to 21 days

• Percentage of Participants with Adverse Events

  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)

  Baseline up to 28 months

Secondary Outcomes (44)

• Serum concentration of RO7122290 over time

  Baseline up to 28 months (detailed time frame provided in description)

• Plasma concentration of RO7122290 over time

  Baseline up to 28 months (detailed time frame provided in description)

• Maximum concentration (Cmax) of RO7122290

  Baseline up to 28 months (detailed time frame provided in description)

• Time of maximum concentration (Tmax) of RO7122290

  Baseline up to 28 months (detailed time frame provided in description)

• Clearance (CL) of RO7122290

  Baseline up to 28 months (detailed time frame provided in description)

Study Arms (2)

Part I: Dose-escalation of RO7122290

EXPERIMENTAL

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.

Drug: RO7122290; Drug: Cibisatamab; Drug: Obinutuzumab

Part II: Dose-expansion of RO7122290

EXPERIMENTAL

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.

Drug: RO7122290; Drug: Cibisatamab; Drug: Obinutuzumab

Interventions

RO7122290 DRUG

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).

Part I: Dose-escalation of RO7122290; Part II: Dose-expansion of RO7122290

Cibisatamab DRUG

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

Part I: Dose-escalation of RO7122290; Part II: Dose-expansion of RO7122290

Obinutuzumab DRUG

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

Part I: Dose-escalation of RO7122290; Part II: Dose-expansion of RO7122290

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma originating from the colon or rectum.
• Metastatic disease (Stage IV American Joint Committee on Cancer, Version 7) not amenable to local treatment.
• Tumors that are MSS (microsatellite-stable) or MSI-low (microsatellite instable low), as determined by a certified laboratory
• Participants with tumors that have high CEACAM5 expression as determined by qRT-PCR in an archival tumor sample or if not available, in a fresh tumor biopsy and documented through central testing of a representative tumor tissue specimen performed at baseline
• Experienced disease progression during or within 3 months following the last administration of approved standard therapies.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1.
• Life expectancy of ≥12 weeks
• Adequate organ functions.
• Serum creatinine within normal limits or a calculated glomerular filtration rate of ≥ 60 mL/min/1.73 m2 for participants with serum creatinine levels above or below the institutional normal value.
• Serum albumin ≥30 g/L (3.0 g/dL).
• Lactate dehydrogenase ≤ 2.5 x ULN.
• Adequate contraception

You may not qualify if:

• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• History of leptomeningeal disease
• Non-irradiated tumor lesions \> 2 cm at critical sites (e.g., paraspinal, paratracheal, mediastinal, precarnial, sub-glottal) where tumor swelling induced by cibisatamab is expected to lead to significant complications. Irradiation must be completed at least 14 days prior to initiation of study treatment.
• Dyspnea or peripheral capillary oxygen saturation \< 92% at rest at baseline for patients with bilateral lung lesions or metastases in the remaining lung following lobectomy or pneumonectomy
• Pleural effusion requiring drainage procedures.
• Pleural effusion and/or pleural lesions involving both lungs
• Active interstitial lung disease (ILD), pneumonitis, or a history of ILD/pneumonitis requiring treatment with steroids or history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
• Patients with \> 10 bilateral pulmonary lesions
• Patients with pulmonary miliary metastatic pattern (innumerable small lesions) or pulmonary lymphangitic carcinomatosis.
• Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of study drug administration
• Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥ 2 weeks prior to initiation of study treatment.
• History of progressive multifocal leukoencephalopathy
• Uncontrolled tumor-related pain.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (13)

Rigshospitalet

København Ø, 2100, Denmark

Location

NKI/AvL

Amsterdam, 1066 CX, Netherlands

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra Madrid

Madrid, 28027, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LJ, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

cibisatamab; obinutuzumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: April 1, 2021
• Study Start: July 14, 2021
• Primary Completion: November 11, 2024
• Study Completion: November 11, 2024
• Last Updated: July 14, 2025

Record last verified: 2025-07

Locations

KR (2); DK (1); ES (7); GB (2); NL (1)