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

• ClinicalTrials.gov Identifier: NCT03866239
• Recruitment Status: Recruiting
• First Posted: March 7, 2019
• Last Update Posted: November 28, 2019
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Drug: Obinutuzumab; Drug: Atezolizumab; Drug: Cibisatamab; Drug: Tocilizumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 46 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib, Multicenter, Open-Label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Cibisatamab in Combination With Atezolizumab After Pretreatment With Obinutuzumab in Patients With Previously Treated Metastatic, Microsatellite-Stable Colorectal Adenocarcinoma With High CEACAM5 Expression
• Actual Study Start Date: May 7, 2019
• Estimated Primary Completion Date: February 11, 2022
• Estimated Study Completion Date: February 11, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: Obinutuzumab Pretreatment (OpT) + Cibisatamab + Atezolizumab; Participants will receive obinutuzumab approximately 2 weeks before receiving atezolizumab and cibisatamab on Day 1 of each treatment cycle (cycle = 21 days).

Drug: Obinutuzumab; 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).; Other Name: Gazyva/Gazyvaro; Drug: Atezolizumab; Atezolizumab will be administered at a fixed of 1200 mg dose by IV infusion on Day 1 of each 21-day cycle until radiographic progression, unacceptable toxicity, or loss of clinical benefit.; Other Name: Tecentriq; Drug: Cibisatamab; 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.; Drug: Tocilizumab; Tocilizumab will be administered by IV infusion as necessary to manage adverse events (AEs)

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 5 years ]
2. Confirmed Objective Response Rate (ORR) [ Time Frame: Baseline up to 5 years ]

Secondary Outcome Measures :

1. Confirmed ORR, as Determined by an Independent Review Facility (IRF) According to Response Evaluation in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Up to 5 years ]
2. Duration of Response (DOR) [ Time Frame: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 5 years) ]
3. Disease Control Rate (DCR) [ Time Frame: Up to 5 years ]
4. Progression Free Survival (PFS) [ Time Frame: From enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 5 years) ]
5. Overall Survival (OS) [ Time Frame: From enrollment to death from any cause (up to 5 years) ]
6. Total Clearance (CL) for Cibisatamab [ Time Frame: At pre-defined intervals from Day 1 to progressive disease and/or treatment discontinuation (up to 5 years) ]
7. Volume of Distribution at Steady State (Vss) of Cibisatamab [ Time Frame: At pre-defined intervals from Day 1 to progressive disease and/or treatment discontinuation (up to 5 years) ]
8. Area Under the Concentration-Time Curve (AUC0-t) for Cibisatamab [ Time Frame: At pre-defined intervals from Day 1 to progressive disease and/or treatment discontinuation (up to 5 years) ]
9. Maximum Serum Concentration (Cmax) of Cibisatamab [ Time Frame: At pre-defined intervals from Day 1 to progressive disease and/or treatment discontinuation (up to 5 years) ]
10. CL of Atezolizumab [ Time Frame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days) ]
11. Vss of Atezolizumab [ Time Frame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days) ]
12. AUC0-t of Atezolizumab [ Time Frame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days) ]
13. Cmax of Atezolizumab [ Time Frame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days) ]
14. CL of Obinutuzumab [ Time Frame: At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days) ]
15. Vss of Obinutuzumab [ Time Frame: At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days) ]
16. AUC0-t of Obinutuzumab [ Time Frame: At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days) ]
17. Cmax of Obinutuzumab [ Time Frame: At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days) ]
18. Incidence of Anti-Drug Antibodies (ADAs) to Cibisatamab [ Time Frame: Baseline up to 5 years ]
19. Incidence of ADAs to Atezolizumab [ Time Frame: Baseline up to 5 years ]
20. Incidence of ADAs to Obinutuzumab [ Time Frame: Baseline up to 5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria

• 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 in a fresh tumor biopsy (for the safety run-in, CEACAM5 expression can be determined on the archival tumor tissue) 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

Additional Inclusion Criteria for patient enrollment into Part 2 of the study:

- No prior treatment with regorafenib or Trifluridine/Tipiracil (TAS-102)

Exclusion criteria

• 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
• Patients 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
• Prior allogeneic stem cell or solid organ transplantation
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of atezolizumab
• Current treatment with anti-viral therapy for HBV
• Treatment with any systemic anti-cancer therapy, including chemotherapy or hormonal therapy, within 28 days prior to initiation of study treatment
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Prior treatment with any of the protocol-specified study treatments
• Prior treatment with T-cell bispecifics (TCBs), including CEACAM5-TCB, CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
• Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better with the exception of alopecia of any grade and Grade <= 2 peripheral neuropathy
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products
• Known allergy or hypersensitivity to any of the study drugs or any of their excipients
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab, within 4 months after the final dose of cibisatamab, within 18 months after the final dose of obinutuzumab, and within 3 months after the final dose of tocilizumab

Contacts and Locations

Contacts

Contact: Reference Study ID Number: CO40939 www.roche.com/about_roche/roche_worldwide.htm; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

Locations

United States, California

Cedars Sinai Medical Center; Not yet recruiting

Los Angeles, California, United States, 90048

UCLA Cancer Center; Not yet recruiting

Santa Monica, California, United States, 90404

Stanford Comprehensive Cancer Center; Not yet recruiting

Stanford, California, United States, 94305

United States, Connecticut

Yale University; Not yet recruiting

New Haven, Connecticut, United States, 06510

United States, Massachusetts

Dana Farber Cancer Institute; Not yet recruiting

Boston, Massachusetts, United States, 02215

United States, New York

New York University Medical Center PRIME; NYU Langone Medical Center; Not yet recruiting

New York, New York, United States, 10016

Columbia University Medical Center; Suspended

New York, New York, United States, 10032

Memorial Sloan-Kettering Cancer Center; Suspended

New York, New York, United States, 10065

United States, North Carolina

Duke Cancer Center; Not yet recruiting

Durham, North Carolina, United States, 27710

United States, Tennessee

Sarah Cannon Research Institute; Not yet recruiting

Nashville, Tennessee, United States, 37203

Vanderbilt Univ Medical Ctr; Not yet recruiting

Nashville, Tennessee, United States, 37203

United States, Texas

MD Anderson Cancer Center; Not yet recruiting

Houston, Texas, United States, 77030

Denmark

Rigshospitalet; Fase 1 Enhed - Onkologi; Recruiting

København Ø, Denmark, 2100

France

Centre Leon Berard; Departement Oncologie Medicale; Not yet recruiting

Lyon, France, 69373

Institut Gustave Roussy; Not yet recruiting

Villejuif, France, 94805

Spain

Clinica Universitaria de Navarra; Servicio de Oncologia; Recruiting

Pamplona, Navarra, Spain, 31008

Hospital Univ Vall d'Hebron; Servicio de Oncologia; Recruiting

Barcelona, Spain, 08035

START Madrid-FJD, Hospital Fundacion Jimenez Diaz; Recruiting

Madrid, Spain, 28040

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03866239 History of Changes
• Other Study ID Numbers: CO40939; 2018-003198-93 ( EudraCT Number )
• First Posted: March 7, 2019
• Last Update Posted: November 28, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com).

Further details on Roche's criteria for eligible studies are available here: https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Adenocarcinoma; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Atezolizumab; Obinutuzumab; Antibodies, Monoclonal; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Immunological