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Colorectal CancerPhase 1NCT03866239

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

A Phase 1 study testing Obinutuzumab, Atezolizumab and Cibisatamab in people with Colorectal Cancer, run by Hoffmann-La Roche at 13 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
Obinutuzumab, Atezolizumab and Cibisatamab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
13 sitesin 4 countries
Study dates
7 May 2019to 13 Mar 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Additional Inclusion Criteria for patient enrollment into Part 2 of the study:
  • No prior treatment with regorafenib or Trifluridine/Tipiracil (TAS-102)

Who cannot join

  • 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
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  • 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
  • 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
  • Participants with pleural effusion requiring drainage procedures
  • Participants with pleural effusion and/or pleural lesions involving both lungs (i.e. bilateral pleural effusions; unliateral pleural effusion with pleural lesion in the contralateral lung)
  • Participants with >10 bilateral pulmonary lesions (i.e. at least one lesion in each lung and more than 10 lung lesions in total)
  • Participants with pulmonary miliary metastatic pattern (innumerable small lesions) or pulmonary lymphangitic carcinomatosis

Trial locations and contacts

13 sites in 4 countries.

13 sites in 4 countries

United States7 sites

  • Duke Cancer Center

    Durham, North Carolina, 27710

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Yale University

    New Haven, Connecticut, 06510

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • UCLA Cancer Center

    Santa Monica, California, 90404

  • Stanford Comprehensive Cancer Center

    Stanford, California, 94305

Other trials in United States

Spain3 sites

  • START Madrid-FJD, Hospital Fundacion Jimenez Diaz

    Madrid, 28040

  • Clinica Universitaria de Navarra; Servicio de Oncologia

    Pamplona, Navarre, 31008

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Sant Andreu de la Barca, Barcelona, 08740

Other trials in Spain

France2 sites

  • Centre Leon Berard; Departement Oncologie Medicale

    Lyon, 69373

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Denmark1 site

  • Rigshospitalet; Fase 1 Enhed - Onkologi

    København Ø, 2100

Other trials in Denmark

About this study

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

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.

Being tested
Obinutuzumab, Atezolizumab, Cibisatamab, Tocilizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ObinutuzumabDrug

    Also called Gazyva/Gazyvaro

    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).

  • AtezolizumabDrug

    Also called Tecentriq

    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.

  • CibisatamabDrug

    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.

  • TocilizumabDrug

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

Study groups in NCT03866239
Study groupRoleWhat they receive
Obinutuzumab Pretreatment (OpT) + Cibisatamab + AtezolizumabExperimentalParticipants will receive obinutuzumab approximately 2 weeks before receiving atezolizumab and cibisatamab on Day 1 of each treatment cycle (cycle = 21 days).
Receives: Drug: Obinutuzumab; Drug: Atezolizumab; Drug: Cibisatamab; Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Adverse Events (AEs)

    Measured: Up to 5 years

  2. Confirmed Objective Response Rate (ORR)

    Measured: Baseline up to 5 years

Secondary outcomes (20)

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

    Measured: Up to 5 years

  2. Duration of Response (DOR)

    Measured: 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)

    Measured: Up to 5 years

  4. Progression Free Survival (PFS)

    Measured: 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)

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

  6. Total Clearance (CL) for Cibisatamab

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: At pre-defined intervals from Day 1 to progressive disease and/or treatment discontinuation (up to 5 years)

  10. CL of Atezolizumab

    Measured: At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days)

  11. Vss of Atezolizumab

    Measured: At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days)

  12. AUC0-t of Atezolizumab

    Measured: At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days)

  13. Cmax of Atezolizumab

    Measured: At pre-defined intervals from Day 1, Cycle 1 through Cycle 8 (cycle = 21 days)

  14. CL of Obinutuzumab

    Measured: At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days)

  15. Vss of Obinutuzumab

    Measured: At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days)

  16. AUC0-t of Obinutuzumab

    Measured: At pre-defined intervals from the start of obinutuzumab pretreatment through Cycle 8 (cycle = 21 days)

  17. Cmax of Obinutuzumab

    Measured: 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

    Measured: Baseline up to 5 years

  19. Incidence of ADAs to Atezolizumab

    Measured: Baseline up to 5 years

  20. Incidence of ADAs to Obinutuzumab

    Measured: Baseline up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2019
  2. Study start7 May 2019
  3. Primary completion13 Mar 2024
  4. Study completion13 Mar 2024

Why it stopped: The Sponsor terminated the study because development of cibisatamab has been discontinued.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03866239
Sponsor's protocol ID
CO40939
Other IDs
2018-003198-93, 2018
Status last verified
Aug 2024
First submitted
6 Mar 2019
Last updated
9 Aug 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). 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).

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Obinutuzumab, Atezolizumab and Cibisatamab in people with Colorectal Cancer, run by Hoffmann-La Roche at 13 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Spain, France, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The Sponsor terminated the study because development of cibisatamab has been discontinued.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with Adverse Events (AEs) (time frame: Up to 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03866239.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.

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