A Phase Ib Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Cibisatamab in Combination With Atezolizumab After Pretreatment With Obinutuzumab in Participants With Previously Treated Metastatic Colorectal Adenocarcinoma

NCT03866239 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CO409392018-003198-93
• Study Type: interventional
• Target: 47
• Locations: 4 countries
• Sites: 13

Brief Summary

CO40939 is a Phase Ib, open-label, multicenter, single-arm study designed to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of cibisatamab in combination with atezolizumab administered after pretreatment with obinutuzumab in patients with Stage IV microsatellite stable (MSS) metastatic colorectal cancer (mCRC) whose tumors have high carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression and who have progressed on two or more chemotherapy regimens. The study is composed of a safety run-in and an exploratory part.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Adverse Events (AEs)

  Up to 5 years

• Confirmed Objective Response Rate (ORR)

  Baseline up to 5 years

Secondary Outcomes (20)

• Confirmed ORR, as Determined by an Independent Review Facility (IRF) According to Response Evaluation in Solid Tumors version 1.1 (RECIST v1.1)

  Up to 5 years

• Duration of Response (DOR)

  From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 5 years)

• Disease Control Rate (DCR)

  Up to 5 years

• Progression Free Survival (PFS)

  From enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 5 years)

• Overall Survival (OS)

  From enrollment to death from any cause (up to 5 years)

Study Arms (1)

Obinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab

EXPERIMENTAL

Participants will receive obinutuzumab approximately 2 weeks before receiving atezolizumab and cibisatamab on Day 1 of each treatment cycle (cycle = 21 days).

Drug: Obinutuzumab; Drug: Atezolizumab; Drug: Cibisatamab; Drug: Tocilizumab

Interventions

Obinutuzumab DRUG

Obinutuzumab will be administered by intravenous (IV) infusion as either a split or single dose approximately 2 weeks before Cycle 1, Day 1 (cycle = 21 days).

Also known as: Gazyva/Gazyvaro

Obinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab

Atezolizumab DRUG

Atezolizumab will be administered at a fixed dose of 1200 mg by IV infusion on Day 1 of each 21-day cycle until radiographic progression, unacceptable toxicity, or loss of clinical benefit.

Also known as: Tecentriq

Obinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab

Cibisatamab DRUG

Cibisatamab will be administered at a fixed dose of 100 mg by IV infusion on Day 1 of each 21-day cycle until radiographic progression, unacceptable toxicity, or loss of clinical benefit.

Obinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab

Tocilizumab DRUG

Tocilizumab will be administered by IV infusion as necessary to manage adverse events (AEs)

Obinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab

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 not amenable to local treatment
• Tumors that are microsatellite stable or microsatellite instability low, as determined by a local, certified laboratory
• Tumors that have high carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression as determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in an archival tumor sample or 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 hematologic and end-organ function
• Negative HIV test at screening
• Negative hepatitis B surface antigen test and total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
• Negative human T-cell lymphotropic virus type 1 test for participants from endemic countries (Japan, countries in the Caribbean basin, South America, Central America, sub-Saharan Africa, and Malaysia)
• For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, agreement to regular pregnancy testing, and agreement to refrain from donating eggs, women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the final dose of atezolizumab, for 4 months after the final dose of cibisatamab, for 18 months after the final dose of obinutuzumab, and for 3 months after the final dose of tocilizumab
• For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, with a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 3 months after the final dose of cibisatamab, for 3 months after the final dose of obinutuzumab, and for 2 months after the final dose of tocilizumab to avoid exposing the embryo
• Lactic acid dehydrogenase (LDH) \</= 2.5 x upper limit of normal (ULN)

You may not qualify if:

• Symptomatic, untreated, or actively progressing central nervous system metastases
• Non-irradiated tumor lesions \> 2 cm at critical sites where tumor swelling induced by cibisatamab is expected to lead to significant complications
• 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
• 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 leptomeningeal disease and progressive multifocal leukoencephalopathy
• Uncontrolled tumor-related pain and pleural effusion or ascites requiring recurrent drainage procedures
• Participants with pericardial effusion
• Uncontrolled or symptomatic hypercalcemia
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
• Active tuberculosis that has required treatment within 3 years prior initiation of study treatment or latent tuberculosis that has not been appropriately treated
• Uncontrolled hypertension, unstable angina, congestive heart failure of any New York Heart Association Class II or greater, serious cardiac arrhythmia requiring treatment and history of myocardial infarction within 6 months prior to initiation of study treatment
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• History of malignancy other than CRC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
• Known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens, or any major episode of infection requiring hospitalization or treatment with IV antibiotics

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (13)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UCLA Cancer Center

Santa Monica, California, 90404, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Rigshospitalet; Fase 1 Enhed - Onkologi

København Ø, 2100, Denmark

Location

Centre Leon Berard; Departement Oncologie Medicale

Lyon, 69373, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Sant Andreu de la Barca, Barcelona, 08740, Spain

Location

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, 31008, Spain

Location

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

obinutuzumab; atezolizumab; cibisatamab; tocilizumab

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: March 7, 2019
• Study Start: May 7, 2019
• Primary Completion: March 13, 2024
• Study Completion: March 13, 2024
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

US (7); FR (2); ES (3); DK (1)