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Solid TumorsPhase 1NCT02650713

A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors

A Phase 1 study testing Atezolizumab and RO6958688 in people with Solid Tumors, run by Hoffmann-La Roche at 24 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab. Part I of the study is subdivided into parts IA and IB. 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?
Atezolizumab and RO6958688
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
228 participants
Where
24 sitesin 7 countries
Study dates
7 Jan 2016to 13 Jan 2020
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

  • Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor lesion of accessible non-critical location to biopsy, in participants who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy
  • Radiologically measurable and clinically evaluable disease (as per RECIST v1.1)
  • Life expectancy (in the opinion of the investigator) of at least 12 weeks and lactate dehydrogenase (LDH) levels </= 2.5 ULN (upper limit of normal)
  • 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, and renal function
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  • Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women </= 2 years after start of menopause (menopause is defined as amenorrhea for more than 2 years)
  • Participants must agree to remain abstinent or be willing to use effective methods of contraception as defined in the protocol
  • Participants with non-colorectal cancer should have confirmed CEA expression in tumor tissue. For colorectal cancer (CRC), the CEA assessment should be performed but the result is not required for participant selection

Who cannot join

  • Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
  • 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 at least 2 weeks prior to enrollment
  • Leptomeningeal disease
  • Participants with paraspinal, paratracheal, and mediastinal pathological lesions larger than 2 cm unless they are previously irradiated
  • Malignancies within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
  • Significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results
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  • Uncontrolled hypertension, unstable angina, congestive heart failure (CHF), serious cardiac arrhythmia requiring treatment history of myocardial infarction within 6 months of enrollment
  • Administration of a live, attenuated vaccine within 28 days before Cycle 1 Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  • Human Inmmunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C (HCV)
  • Severe infections within 28 days prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia or active tuberculosis
  • Received oral or intravenous (IV) antibiotics within 14 days prior to Day 1
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
  • Major surgery or significant traumatic injury less than 28 days prior to Cycle 1 Day 1 (excluding biopsies) or anticipation of the need for major surgery during study treatment
  • Known history of autoimmune disease as defined in the protocol
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis (including drug induced) on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Participants with bilateral lung lesions and dyspnea and/or oxygen saturation level (SaO2) less than 92% (at rest, room air and exertion) or participants with lobectomy or pneumonectomy with lung metastases in the remaining lung and either dyspnea or SaO2 less than 92% (at rest, room air and exertion) at baseline
  • Pregnant or breast-feeding
  • Known hypersensitivity to any of the components of RO6958688 and atezolizumab; hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Investigational therapy (defined as treatment for which there is no regulatory authority approved indication) or last dose of prior immunotherapies within 28 days prior to Cycle 1 Day 1. Participants previously treated with anti-programmed death-ligand 1 (PD-L1), or anti-PD-1 are excluded
  • Last dose of any approved anti-cancer therapy within 28 days prior to the first RO6958688 infusion
  • Prior systemic corticosteroids greater than 10mg prednisone (or equivalent) within 14 days of Cycle 1 Day 1. Inhaled and/or topical steroids are permitted
  • Expected need for regular immunosuppressive therapy
  • Radiotherapy within the last 28 days before Cycle 1 Day 1 with the exception of limited-field palliative radiotherapy

Trial locations and contacts

24 sites in 7 countries.

24 sites in 7 countries

United States11 sites

  • University Of Colorado

    Aurora, Colorado, 80045

  • Dana Farber Can Ins

    Boston, Massachusetts, 02215

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Duke Cancer Center

    Durham, North Carolina, 27710

  • Sarah Cannon Cancer Center

    Germantown, Tennessee, 38138

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Smilow Cancer Hospital at Yale- New Haven Oncology Investigational Drug Pharmacy

    New Haven, Connecticut, 06510

  • Columbia Univ Med Ctr

    New York, New York, 10032

  • 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

Spain6 sites

  • Hospital del Mar; Servicio de Oncologia

    Barcelona, 08003

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, 08035

  • START Madrid-FJD, Hospital Fundacion Jimenez Diaz

    Madrid, 28040

  • Hospital Universitario 12 de Octubre; Servicio de Oncologia

    Madrid, 28041

  • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

    Madrid, 28050

  • Clinica Universitaria de Navarra; Servicio de Oncologia

    Pamplona, Navarre, 31008

Other trials in Spain

France2 sites

  • Centre Leon Berard; Departement Oncologie Medicale

    Lyon, 69373

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Italy2 sites

  • IRCCS IST. Tumori Fondaz. Pascale; S.C. Oncologia Medica,Melanoma,Immunoterapia E Terapie Innovative

    Naples, Campania, 80131

  • Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica

    Siena, Tuscany, 53100

Other trials in Italy

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

Netherlands1 site

  • Antoni Van Leeuwenhoek Ziekenhuis; Gastro-Enterologie

    Amsterdam, 1066 CX

Other trials in Netherlands

About this study

Official title: An Open-Label, Multicenter, Dose Escalation and Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors

This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab. Part I of the study is subdivided into parts IA and IB. Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab. Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.

Conditions
Solid Tumors
Being tested
Atezolizumab, RO6958688

What participants receive

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

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.

  • RO6958688Drug

    RO6958688 is administered by IV infusion

    In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle.

    In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W.

    Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower.

Study groups in NCT02650713
Study groupRoleWhat they receive
Dose-Escalation (Part IA): RO6958688 + AtezolizumabExperimentalParticipants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W). RO6958688 dosage will not exceed the MTD if defined in the BP29541 study.
Receives: Drug: Atezolizumab; Drug: RO6958688
Dose/Schedule Finding (Part IB): RO6958688 + AtezolizumabExperimentalPart IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of: Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688. Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first.
Receives: Drug: Atezolizumab; Drug: RO6958688

What is being measured

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

  1. Number of Participants with Adverse Events (AEs)

    Measured: Baseline up to 60 months

  2. Percentage of Participants with Dose-Limiting Toxicities (DLTs)

    Measured: Day 1 up to Day 21

  3. Maximum-Tolerated Dose (MTD) of RO6958688

    Measured: Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation

  4. Recommended Phase II Dose (RP2D) of RO6958688

    Measured: Day 1 up to 60 months

Secondary outcomes (16)

  1. Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688

    Measured: Baseline up to 60 months

  2. PK: Volume of Distribution at Steady State (Vss) of RO6958688

    Measured: Baseline up to 60 months

  3. PK: Maximum Serum Concentration (Cmax) of RO6958688

    Measured: Baseline up to 60 months

  4. PK: Clearance (CL) of RO6958688

    Measured: Baseline up to 60 months

  5. PK: AUC of Atezolizumab

    Measured: Baseline up to 60 months

  6. PK: Vss of Atezolizumab

    Measured: Baseline up to 60 months

  7. PK: Cmax of Atezolizumab

    Measured: Baseline up to 60 months

  8. PK: CL of Atezolizumab

    Measured: Baseline up to 60 months

  9. Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry

    Measured: Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days)

  10. Percentage of Participants with Objective Response (Partial Response [PR] or Complete Response [CR] as Assessed Using Response Evaluation Criteria in Solid Tumors [RECIST])

    Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.

    Measured: Baseline up to 60 months

  11. Percentage of Participants with Disease Control (PR, CR, or Stable Disease [SD]) as Assessed Using RECIST

    Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.

    Measured: Baseline up to 60 months

  12. Percentage of Participants with Stable Disease (SD) as Assessed Using RECIST

    Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.

    Measured: Baseline up to 60 months

  13. Duration of Response (DOR) as Assessed Using RECIST

    Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.

    Measured: From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)

  14. Progression-Free Survival (PFS) according to RECIST V1.1

    Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.

    Measured: From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)

  15. Overall Survival (OS)

    Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.

    Measured: From first study treatment to death from any cause (up to 60 months)

  16. Best Overall Response (BOR)

    Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.

    Measured: Baseline up to 60 months

Timeline

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

  1. First posted8 Jan 2016 (estimated)
  2. Study start7 Jan 2016
  3. Primary completion13 Jan 2020
  4. Study completion13 Jan 2020

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
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
228 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02650713
Sponsor's protocol ID
WP29945
Other IDs
RG7802, 2015-003771-30, 2015
Status last verified
Feb 2020
First submitted
6 Jan 2016
Last updated
12 Feb 2020
Results posted
No
Data monitoring committee
No

Publications

  • Martinez-Sabadell A, Morancho B, Rius Ruiz I, Roman Alonso M, Ovejero Romero P, Escorihuela M, Chicote I, Palmer HG, Nonell L, Alemany-Chavarria M, Klein C, Bacac M, Arribas J, Arenas EJ. The target antigen determines the mechanism of acquired resistance to T cell-based therapies. Cell Rep. 2022 Oct 18;41(3):111430. doi: 10.1016/j.celrep.2022.111430.

    PubMed 36261015

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab and RO6958688 in people with Solid Tumors, run by Hoffmann-La Roche at 24 sites in 7 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 9 inclusion and 23 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: finished, as of the sponsor's last update on 12 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Spain, France, Italy, Canada and 2 more countries. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 Adverse Events (AEs) (time frame: Baseline up to 60 months). The study lists 4 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 NCT02650713, which also lists 1 linked publication.

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 12 Feb 2020.

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