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A Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (PD-L1 Antibody) in Participants With Advanced Ovarian Cancer or Triple Negative Breast Cancer

NCT03292172

Description:

This is Phase IB, open label, non-randomized study designed to investigate the dose, safety, pharmacokinetics and anti-tumor activity of RO6870810 in combination with a fixed dose of atezolizumab. The study consists of four groups, Group 1 (Dose Escalation Group) and Group 2 (Sequential Dose Group), and Groups 3 and 4 (Expansion Groups), which will further evaluate the safety, pharmacokinetic, pharmacodynamic and preliminary clinical activity in patients with triple negaive breast cancer and/or ovarian cancer.

Related Conditions:
  • Breast Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (PD-L1 Antibody) in Participants With Advanced Ovarian Cancer or Triple Negative Breast Cancer
  • Official Title: Open Label, Dose Finding Phase IB Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of RO6870810 and Atezolizumab (Pd L1 Antibody) in Pateints With Advanced Ovarian Cancer or Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: NP39487
  • SECONDARY ID: 2017-001147-13
  • NCT ID: NCT03292172

Conditions

  • Advanced Ovarian Cancer
  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
AtezolizumabEscalation Dose: RO6870810 + Atezolizumab
RO6870810Escalation Dose: RO6870810 + Atezolizumab

Purpose

This is Phase IB, open label, non-randomized study designed to investigate the dose, safety, pharmacokinetics and anti-tumor activity of RO6870810 in combination with a fixed dose of atezolizumab. The study consists of two groups, Group 1 (Dose Escalation Group) and Group 2 (Sequential Dose Group).

Trial Arms

NameTypeDescriptionInterventions
Escalation Dose: RO6870810 + AtezolizumabExperimentalParticipants will be administered escalating doses of RO6870810 (0.3 milligram per kilogram [mg/kg], 0.45 mg/kg, and 0.65 mg/kg) subcutaneously (SC) once daily (QD) along with fixed dose of atezolizumab 1200 mg intravenously (IV) on Day 1 of each cycle (21 day cycles), every 3 weeks. RO6870810 will be given during the first 14 days.
  • Atezolizumab
  • RO6870810
Sequential Dose: RO6870810 + AtezolizumabExperimentalParticipants will be administered RO6870810 monotherapy (starting dose 0.30 mg/kg) during the first 14 days of 21-day Run-in period. Following the Run-in period, participants will continue to receive RO6870810 at the same dose in combination with fixed dose of atezolizumab 1200 mg IV every 3 weeks in 21-day cycles.
  • Atezolizumab
  • RO6870810

Eligibility Criteria

        Inclusion Criteria:-

          -  Participants with histologically confirmed advanced ovarian cancer or triple negative
             breast cancer who in the opinion of the Investigator are appropriate for this study

          -  Measurable disease by RECIST criteria version 1.1 prior to study drug administration

          -  Performance status of 0 or 1 on the eastern Cooperative Oncology Group (ECOG) scale

          -  Life expectancy, in the opinion of the Investigator, of at least 3 months

          -  Disease-free of active second/secondary or prior malignancies for => 2 years with the
             exception of squamous cell carcinoma of the skin, or carcinoma in situ of the cervix
             or breast

          -  Willing to provide the protocol specified tumor biopsies

          -  Acceptable hematologic status, liver and renal function

          -  Participants who have received prior treatment with CD137 agonists or immune
             checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1
             therapeutic antibodies, may be enrolled, provided the following requirements are met:

               -  Minimum of 5 months from the last dose of anti-PD-1, anti-CTLA-4, anti-PD- L1 or
                  CD137 agonist treatment

               -  No history of severe immune-related adverse effects from CD137 agonist,
                  anti−CTLA-4, anti-PD-1 or anti-PD-L1 (NCI CTCAE Grade 3 and 4). Any toxicity
                  related to the therapy must have resolved completely, no residual toxicity as
                  assessed by NCI CTCAE (v4.03)

          -  Agree to use protocol defined methods of contraception

        Exclusion Criteria:

          -  Participants with history of prior malignancy except solid tumor treated curatively
             more than 3 years ago without evidence of recurrence

          -  Asymptomatic or symptomatic, untreated, or actively progressing central nervous system
             (CNS) metastases

          -  History of leptomeningeal disease

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures. Participants with indwelling catheters are allowed.

          -  Uncontrolled or symptomatic hypercalcemia

          -  New York Heart Association Class III or IV cardiac disease, pericarditis, myocardial
             infarction within the past 6 months, unstable arrhythmia

          -  Fredericia-corrected QT interval (QTcF) > 470 milli seconds (msec) (female) or > 450
             msec (male), or history of congenital long QT syndrome. Any electrocardiogram (ECG)
             abnormality, including pericarditis, which in the opinion of the Investigator would
             preclude safe participation in the study.

          -  Active, uncontrolled bacterial, viral, or fungal infections within 7 days of study
             entry requiring systemic therapy

          -  Known clinically important respiratory impairment

          -  History of major organ transplant

          -  History of an autologous or allogeneic bone marrow transplant

          -  Serious non-malignant disease that could compromise protocol objectives in the opinion
             of the Investigator and/or the Sponsor

          -  Pregnant or nursing women

          -  Any systemic anticancer therapy within 3 weeks prior to Cycle 1 Day 1

          -  Any radiation treatment to metastatic site within <= 14 days of Cycle 1 Day 1

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 30 days
             prior to Cycle 1 Day 1 or anticipation of need for major surgical procedure during the
             course of the study

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
             ovary cells or any component of the atezolizumab formulation

          -  Active or history of autoimmune disease

          -  History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
             pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
             organizing pneumonia), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan. History of radiation pneumonitis in the radiation field
             (fibrosis) is permitted

          -  Positive test for Human immunodeficiency virus (HIV)

          -  Active hepatitis B or hepatitis C

          -  Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or
             anticipation that such a live, attenuated vaccine will be required during the study

          -  Treatment with investigational therapy within 28 days prior to initiation of study
             treatment

          -  Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
             of study treatment

          -  Consumption of agents which strongly inhibit CYP3A4 enzyme, within 7 days prior to the
             first dose of study treatment and during the study

          -  Consumption of agents which strongly induce CYP3A4 enzyme, within 14 days prior to the
             first dose of study treatment and during the study

          -  Treatment with systemic immuno-stimulatory agents within 4 weeks or five half-lives of
             the drug (whichever is shorter) prior to the first dose of study treatment

          -  Treatment with systemic corticosteroids or other systemic immunosuppressive
             medications within 2 weeks prior to the first dose of study treatment, or, anticipated
             requirement for systemic immunosuppressive medications during the trial

          -  History of allergic reactions attributed to components of the formulated product(s)

          -  Unwillingness or inability to comply with procedures required in this protocol
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Dose Limiting Toxicities (DLT)
Time Frame:Cycle 1 (Day 21)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maximum concentration (Cmax) of RO6870810 (RO) and Atezolizumab (Ate)
Time Frame:RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Safety Issue:
Description:
Measure:Time of maximum concentration (tmax) of RO6870810 and Atezolizumab
Time Frame:RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Safety Issue:
Description:
Measure:Clearance (CL) or Apparent Clearance (CL/F) of RO6870810 and Atezolizumab
Time Frame:RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Safety Issue:
Description:
Measure:Volume of Distribution (Vd) or Apparent Volume of Distribution (Vd/F) of RO6870810 and Atezolizumab
Time Frame:RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Safety Issue:
Description:
Measure:Area Under the Plasma Concentration-Time Curve From Time Zero to End of the Dosing Interval (AUC0-tau) of RO6870810 and Atezolizumab
Time Frame:RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Safety Issue:
Description:
Measure:Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of RO6870810 and Atezolizumab
Time Frame:RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Safety Issue:
Description:
Measure:Half life (t1/2) of RO6870810 and Atezolizumab
Time Frame:RO: Pre-dose Day 1,14,21;0.25,0.5,1,2,4,6,8,10hour (h) post-dose Day 14;24,28h post-dose Day 15 Run-in, Cycle 1, even cycles till end of treatment; Ate: pre-dose, end of infusion Day 1 Cycle 1; pre-dose Day 1 of even cycles; follow-up (Up to 22 months)
Safety Issue:
Description:
Measure:Trough concentration (Ctrough) of RO6870810 and Atezolizumab
Time Frame:Pre-dose at Cycle 2 and at the beginning of every subsequent even-number cycles (Up to 22 months)
Safety Issue:
Description:
Measure:Objective Response (OR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time Frame:From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Safety Issue:
Description:
Measure:Objective Response (OR) as per Immune-Modified RECIST
Time Frame:From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Safety Issue:
Description:
Measure:Duration of Response (DoR) as per RECIST v1.1 and Immune-Modified RECIST
Time Frame:From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS) per RECIST v1.1 and Immune-Modified RECIST
Time Frame:From first occurrence of objective response until disease progression or death from any cause (Up to 22 months)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:From the time of first dose of study treatment to the time of death from any cause (Up to 22 months)
Safety Issue:
Description:
Measure:Tumor Marker Assessments (CA-125, According to Modified Gynecologic Cancer InterGroup [GCIG] Guidelines,CEA, CA15-3 Changes)
Time Frame:Day 1 of each cycle till end of treatment or disease progression or death from any cause (Up to 22 months)
Safety Issue:
Description:
Measure:Changes in CD11b Expression Levels Measurement in CD14+ Monocytes From Blood Association with Steady-State RO6870810 PK Drug Exposure
Time Frame:Day 1, 8, 15, 21 of Run-in period , Cycle 1
Safety Issue:
Description:
Measure:Changes in T-cell Markers (e.g., PD-L1, CD8/Ki 67) in Tissue Biopsy Specimens by Immunohistochemistry (IHC)
Time Frame:Day 1, 15, 21 of Run-in period, Cycle 1
Safety Issue:
Description:
Measure:Percentage of Participants With Transcript Profiling Assessment Receiving Combination Study Treatment
Time Frame:Pre-dose Day 1, 21 Run-in period, Cycle 1; 6h post-dose Day 1 Run-in period, Cycle 1
Safety Issue:
Description:

Details

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

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