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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

NCT02650713

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: WP29945
  • SECONDARY ID: RG7802
  • SECONDARY ID: 2015-003771-30
  • NCT ID: NCT02650713

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
AtezolizumabTecentriqDose-Escalation (Part IA): RO6958688 + Atezolizumab
RO6958688Dose-Escalation (Part IA): RO6958688 + Atezolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
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.
  • Atezolizumab
  • 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.
  • Atezolizumab
  • RO6958688

Eligibility Criteria

        Inclusion Criteria

          -  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

          -  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

        Exclusion Criteria

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Adverse Events (AEs)
Time Frame:Baseline up to 60 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688
Time Frame:Baseline up to 60 months
Safety Issue:
Description:
Measure:PK: Volume of Distribution at Steady State (Vss) of RO6958688
Time Frame:Baseline up to 60 months
Safety Issue:
Description:
Measure:PK: Maximum Serum Concentration (Cmax) of RO6958688
Time Frame:Baseline up to 60 months
Safety Issue:
Description:
Measure:PK: Clearance (CL) of RO6958688
Time Frame:Baseline up to 60 months
Safety Issue:
Description:
Measure:PK: AUC of Atezolizumab
Time Frame:Baseline up to 60 months
Safety Issue:
Description:
Measure:PK: Vss of Atezolizumab
Time Frame:Baseline up to 60 months
Safety Issue:
Description:
Measure:PK: Cmax of Atezolizumab
Time Frame:Baseline up to 60 months
Safety Issue:
Description:
Measure:PK: CL of Atezolizumab
Time Frame:Baseline up to 60 months
Safety Issue:
Description:
Measure:Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry
Time Frame: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)
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response (Partial Response [PR] or Complete Response [CR] as Assessed Using Response Evaluation Criteria in Solid Tumors [RECIST])
Time Frame:Baseline up to 60 months
Safety Issue:
Description: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.
Measure:Percentage of Participants with Disease Control (PR, CR, or Stable Disease [SD]) as Assessed Using RECIST
Time Frame:Baseline up to 60 months
Safety Issue:
Description: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.
Measure:Percentage of Participants with Stable Disease (SD) as Assessed Using RECIST
Time Frame:Baseline up to 60 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR) as Assessed Using RECIST
Time Frame:From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
Safety Issue:
Description: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.
Measure:Progression-Free Survival (PFS) according to RECIST V1.1
Time Frame:From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:From first study treatment to death from any cause (up to 60 months)
Safety Issue:
Description: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.
Measure:Best Overall Response (BOR)
Time Frame:Baseline up to 60 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Hoffmann-La Roche

Last Updated

February 12, 2020