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Solid TumorsPhase 1NCT03539484

A Study of RO7172508 in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors

A Phase 1 study testing RO7172508, Obinutuzumab and Tocilizumab in people with Solid Tumors, run by Hoffmann-La Roche at 6 sites in 4 countries.

Terminated

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

Official record
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Trial summary

This study was to determine the maximum-tolerated dose (MTD) and/or the optimal biological dose (OBD) as well as the optimal schedule for intravenous (IV) and subcutaneous (SC) administrations of RO7172508 as monotherapy, with or without obinutuzumab pre-treatment, in participants with locally advanced and/or… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
RO7172508, Obinutuzumab and Tocilizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
6 sitesin 4 countries
Study dates
4 Jul 2018to 22 Jul 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • For Part I: participants with locally advanced and/or metastatic solid tumor with confirmed cytoplasmic and/or membranous high CEA expression in tumor tissue is required. Participants must have progressed on a SOC therapy, be intolerant to SOC, and/or are non-amenable to SOC.
  • For <12 mg dose cohorts, serum CEA levels below a certain threshold is required as follows:
  • For dose cohorts 65-159 microgram, a sCEA level of < 22 ng/mL
  • For dose cohorts 160-399 microgram, a sCEA level of < 28 ng/mL
  • For dose cohorts 400-799 microgram, a sCEA level of < 44 ng/mL
  • For dose cohorts 800-1599 microgram, a sCEA level of < 70 ng/mL
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  • For the dose cohort of 1.6-3.1 milligram, a sCEA level of < 123 ng/mL
  • For the dose cohort of 3.2-6.3 milligram, an sCEA level of < 229 ng/mL.
  • For the dose cohort of 6.4-11.9 milligram, an sCEA level of < 440 ng/mL. If dose fractionation is implemented, the sCEA threshold for inclusion should correspond to the dose range of the first dose administered.
  • For Part II, participants with locally advanced and/or metastatic solid tumor expressing cytoplasmic and/or membranous high-CEA or moderate/low-CEA on archival material, who have progressed on a SOC therapy, are intolerant to SOC, and/or are non-amenable to SOC. Participants must have a lesion amenable to biopsy (except participants with NSCLC, which may be enrolled with archival tissue available only). For participants with colorectal cancer (CRC) only, the CEA assessment by immunohistochemistry should be performed but the result is not required to enroll the participant.
  • Radiologically measurable disease according to RECIST v1.1.
  • Life expectancy of >= 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
  • All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade <= 1 or returned to baseline except alopecia (any grade) and Grade 2 peripheral neuropathy.
  • Adequate hematological, liver, renal, and lung function
  • For women: agree to remain abstinent or use two contraceptive methods that result in a failure rate of <1% per year from screening until 2 months after the last dose of RO7172508 and have a negative pregnancy test within one week prior to the first study treatment administration
  • For men: remain abstinent or use contraceptive measures such as a condom plus an additional contraceptive method that together result in a failure rate of <1% per year, with partners who are woman of childbearing potential and refrain from donating sperm during the study

Who cannot join

  • History or clinical evidence of central nervous system (CNS) primary tumors or metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days before screening.
  • Non-irradiated lesions > 2 cm at critical sites where tumor swelling induced by RO7172508 is expected to lead to significant complications.
  • Another invasive malignancy in the last 2 years
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or contraindicate the use of an investigational drug.
  • Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia that requires treatment with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia, and history of myocardial infarction within 6 months of enrollment.
  • Active or uncontrolled infections.
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  • Known hepatitis B or C
  • Major surgery or significant traumatic injury < 28 days prior to the first RO7172508 administration or anticipation of the need for major surgery during study treatment.
  • Specific Exclusion Criteria if Pre-treatment with Obinutuzumab is Implemented:
  • Known HIV
  • Positive test results for HBV infection, HBcAb indicating an active viral infection and positive test results for HCV.
  • Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
  • History of progressive multifocal leukoencephalopathy.
  • Active TB requiring treatment within 3 years prior to baseline.
  • Latent TB diagnosed during Screening.
  • Positive test results for human T-lymphotropic virus 1

Trial locations and contacts

6 sites in 4 countries.

6 sites in 4 countries

Spain3 sites
  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, 08035

  • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

    Madrid, 28050

  • Clinica Universitaria de Navarra

    Pamplona, Navarre, 31008

Other trials in Spain

Belgium1 site
  • Cliniques Universitaires St-Luc

    Brussels, 1200

Other trials in Belgium

Canada1 site
  • Princess Margaret Cancer Center

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

Denmark1 site
  • Rigshospitalet; Onkologisk Klinik

    København Ø, 2100

Other trials in Denmark

About this study

Official title: A First-in-Human, Open-Label, Multicenter, Dose-Escalation Phase I Clinical Study of Single-Agent RO7172508 in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors

This study was to determine the maximum-tolerated dose (MTD) and/or the optimal biological dose (OBD) as well as the optimal schedule for intravenous (IV) and subcutaneous (SC) administrations of RO7172508 as monotherapy, with or without obinutuzumab pre-treatment, in participants with locally advanced and/or metastatic carcinoembryonic antigen (CEA)-positive solid tumors who have progressed on standard of care (SOC) treatment, are intolerant to SOC, and/or are non-amenable to SOC. This study was conducted in two parts. Part I of the study consisted of an IV single participant cohort/multiple-ascending dose-escalation to evaluate the safety of RO7172508. Part II was a multiple participant cohort/multiple-ascending dose-escalation to define the MTD and/or OBD of RO7172508 administered as single agent, IV and/or SC, in participants with tumors that are expressing high as well as moderate/low-CEA. The study switched from Part I to Part II when the maximum planned dose for Part I was reached or the occurrence of a RO7172508-related Grade >= 2 adverse event (AE) or dose-limiting toxicity (DLT) was observed, whichever comes first. The Sponsor may decide to switch from Part I to Part II in the absence of an observed RO7172508-related Grade >= 2 toxicity or prior to maximum planned dose for Part I.

Conditions
Solid Tumors
Being tested
RO7172508, Obinutuzumab, Tocilizumab

What participants receive

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

  • RO7172508Drug

    RO7172508 was administered at a dose and as per the schedule specified in the respective arms.

  • ObinutuzumabDrug

    In the event obinutuzumab treatment is implemented, obinutuzumab will be administered either on Day-7 or on Day-7 and Day-6. If obinutuzumab is given only on one day, then the schedule for Day-7 should be followed including an end of infusion sample.

  • TocilizumabDrug

    Tocilizumab was administered if required, for the management of severe CRS (cytokine release syndrome)

Study groups in NCT03539484
Study groupRoleWhat they receive
Part I: Single Participant Cohorts IV/MAD-EscalationExperimentalPart I was a multiple-ascending dose-escalation in single participant cohorts. RO7172508 was administered intravenously once every 3 weeks (Q3W). The starting dose of RO7172508 was 65 microgram (mcg) and the maximum dose explored was 1.6 milligram (mg).
Receives: Drug: RO7172508; Drug: Tocilizumab
Part II: Multiple Participant Cohorts IV/MAD-EscalationExperimentalMultiple ascending dose-escalation of IV-administered RO7172508 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation was determined by Part I and RO7172508 was initially given Q3W. Dose-escalation was undertaken based on safety until determination of the MTD or the highest safe dose if MTD is not reached. If on-target toxicity was reported in the first cycle of treatment, fractionated dosing may be implemented for the first cycle to improve tolerability.
Receives: Drug: RO7172508; Drug: Obinutuzumab; Drug: Tocilizumab
Part II: Multiple Participant Cohorts SC/MAD-Escalation (QW)ExperimentalMultiple ascending dose-escalation of SC-administered RO7172508 in multiple participant cohorts. These will be initiated once the IV schedule has shown RO7172508 preliminary clinical activity or the MTD has been established and is equal to or above 2 mg. The starting-dose and regimen once a week or once every 3 weeks (QW or Q3W) for SC administration will be proposed based on the evaluation of the safety and PK data observed following IV administration but will not exceed the highest safe dose tested in the IV Q3W dose escalation; a minimum dose of 2 mg is defined for a single SC administration. In addition, the QW SC starting-dose will not exceed one third of the IV MTD or of the highest safe IV dose tested. Dose escalation will continue based on safety until determination of the MTD or the planned maximum dose of 400 mg. If on-target toxicity is reported in the first cycle of treatment, fractionated dosing may be implemented for the first cycle to improve tolerability.
Receives: Drug: RO7172508; Drug: Obinutuzumab; Drug: Tocilizumab

What is being measured

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

  1. Number of Participants With Dose Limiting Toxicities (DLTs)

    Number of participants with DLTs.

    Measured: Up to approximately 12 months

  2. Percentage of Participants With Adverse Events

    Percentage of participants with adverse events.

    Measured: 60 days after last dose of study treatment (up to approximately 12 months)

Secondary outcomes (17)
  1. Maximum Concentration of RO7172508

    Measured: Cycle 1 following single dose administration of RO7172508

  2. Time of Maximum Concentration of RO7172508

    Measured: Cycle 1 following single dose administration of RO7172508

  3. Clearance or Apparent Clearance of RO7172508

    Measured: Cycle 1 following single dose administration of RO7172508

  4. Volume of Distribution at Steady State of RO7172508

    Measured: Cycle 1 following single dose administration of RO7172508

  5. Area Under the Plasma Concentration Time-Curve From Zero to the Last Measured Concentration (AUClast) of RO7172508

    Measured: Cycle 1 following single dose administration of RO7172508

  6. Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf) of RO7172508

    Measured: Cycle 1 following single dose administration of RO7172508

  7. Dose Normalized Area Under the Serum Concentration Versus Time Curve Computed From Time of Dosing to Infinity (AUCinf/Dose) of RO7172508

    Measured: Cycle 1 following single dose administration of RO7172508

  8. Half-Life of RO7172508

    Measured: Cycle 1 following single dose administration of RO7172508

  9. Presence or Absence and Titer of ADAs

    Measured: Up to approximately 12 months

  10. Changes in Frequency of Tumor Infiltrating Lymphocytes

    Measured: Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)

  11. Secondary: Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD8)

    Measured: Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)

  12. Changes in Activation Status of Tumor Infiltrating Lymphocytes (% of CD4)

    Measured: Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)

  13. Changes in Spatial Distribution of Tumor Infiltrating Lymphocytes

    Spatial distribution of TIL's analyzed by performing IHC assay, which measures the density and intra-tumoral location of CD8+ T cells and reports "CD8 T cell immune phenotypes". These are classified as "desert", "excluded" and "inflamed".

    Measured: Cycle 1 Day 1 (Pre-treatment), Cycle 2 Day 8 (Cycle is 21 days)

  14. Objective Response Rate (ORR)

    Objective response was defined as a Complete Response (CR) or Parital Response (PR), as determined by the Investigator's assessment using RECIST v1.1 and confirmed by repeat assessments >= 4 weeks after initial documentation. To classify a response as SD, measurements are classified as stable (according to RECIST v1.1) at least once after study entry at a minimum of 6 weeks after study entry.

    Measured: Up to approximately 12 months

  15. Disease Control Rate (DCR)

    DCR is determined as the rate of participants with an observed tumor response of CR or PR (ORR) or CR, PR or SD (DCR). DCR is to be derived for RECIST v1.1.

    Measured: Up to approximately 12 months

  16. Duration of Response (DOR)

    Among participants with an objective response (responders), DOR will be defined as the time from first occurrence of a documented objective response until the time of documented disease progression or death within 30 days from last study treatment from any cause during treatment, whichever occurs first. This will be calculated for participants who have a best overall response of CR or PR as defined per RECIST v1.1 and per iRECIST.

    Measured: Up to approximately 12 month

  17. Progression Free Survival (PFS)

    PFS (on-treatment) will be defined as the time from study treatment initiation (Cycle 1 Day 1) to the first occurrence of documented disease progression or death from any cause during treatment (death within 30 days from last study treatment), whichever occurs first.

    Measured: Up to approxmately 12 months

Timeline

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

  1. First posted29 May 2018
  2. Study start4 Jul 2018
  3. Primary completion22 Jul 2019
  4. Study completion22 Jul 2019

Why it stopped: Study terminated due to change in benefit-risk ratio, driven by high incidence GI toxicity in absence of clinically significant anti-tumor efficacy.

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03539484
Sponsor's protocol ID
BP40092
Status last verified
Aug 2020
First submitted
19 Apr 2018
Last updated
3 Sep 2020
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RO7172508, Obinutuzumab and Tocilizumab in people with Solid Tumors, run by Hoffmann-La Roche at 6 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 16 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 3 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Spain, Belgium, Canada, 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?

Yes. Results are posted in the registry (first posted 3 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Up to approximately 12 months). 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?
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 3 Sep 2020.

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