Clinical Trials /

A Study of RO7198457 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors

NCT03289962

Description:

This is a Phase 1a/1b, open-label, multicenter, global, dose-escalation study designed to evaluate the safety, tolerability, immune response, and pharmacokinetics of RO7198457 as a single agent and in combination with atezolizumab (MPDL3280A, an engineered anti-programmed death-ligand 1 [anti-PD-L1] antibody).

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Merkel Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of RO7198457 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Tumors
  • Official Title: A Phase 1a/1b Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of RO7198457 as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Tumors

Clinical Trial IDs

  • ORG STUDY ID: GO39733
  • SECONDARY ID: 2017-001475-23
  • NCT ID: NCT03289962

Conditions

  • Melanoma
  • Non-Small Cell Lung Cancer
  • Bladder Cancer
  • Colorectal Cancer
  • Triple Negative Breast Cancer
  • Renal Cancer
  • Head and Neck Cancer
  • Other Solid Cancers

Interventions

DrugSynonymsArms
RO7198457Phase 1a Dose-Escalation: RO7198457
AtezolizumabTecentriq, RO5541267, MPDL3280A, An engineered anti-PDL1 antibodyPhase 1b Dose-Escalation: RO7198457 + Atezolizumab

Purpose

This is a Phase 1a/1b, open-label, multicenter, global, dose-escalation study designed to evaluate the safety, tolerability, immune response, and pharmacokinetics of RO7198457 as a single agent and in combination with atezolizumab (MPDL3280A, an engineered anti-programmed death-ligand 1 [anti-PD-L1] antibody).

Trial Arms

NameTypeDescriptionInterventions
Phase 1a Dose-Escalation: RO7198457ExperimentalParticipants will receive RO7198457 at escalated dosages.
  • RO7198457
Phase 1b Dose-Escalation: RO7198457 + AtezolizumabExperimentalParticipants will receive RO7198457 at escalated dosages along with atezolizumab at a fixed dose of 1200 milligrams (mg).
  • RO7198457
  • Atezolizumab
Phase 1b Exploration: RO7198457 + AtezolizumabExperimentalNon-small cell lung cancer (NSCLC) or Melanoma cancer immunotherapy (CIT)-treated participants will receive RO7198457 (at dosage lower than maximum tolerated dose [MTD] based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.
  • RO7198457
  • Atezolizumab
Phase 1b Expansion: RO7198457 + AtezolizumabExperimentalParticipants with different indications as per inclusion criteria, will receive RO7198457 (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.
  • RO7198457
  • Atezolizumab
Phase 1b Expansion: RO7198457 + Atezolizumab (Serial Biopsy)ExperimentalCIT-naive participants with selected tumor types who consent to optional serial biopsies will receive RO7198457 (at multiple dose levels below MTD based on available safety data) along with atezolizumab at a fixed dose of 1200 mg.
  • RO7198457
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Life expectancy greater than or equal to (>=12 weeks)

          -  Adequate hematologic and end-organ function

          -  Measured or calculated creatinine clearance >=50 milliliters per minute (mL/min) on
             the basis of the Cockcroft-Gault glomerular filtration rate estimation

        Cancer-Specific Inclusion Criteria:

          -  Participants with histologic documentation of locally advanced, recurrent, or
             metastatic incurable malignancy that has progressed after at least one available
             standard therapy; or for whom standard therapy has proven to be ineffective or
             intolerable, or is considered inappropriate; or for whom a clinical trial of an
             investigational agent is a recognized standard of care

          -  Participants with confirmed availability of representative tumor specimens in
             formalin-fixed, paraffin-embedded (FFPE) blocks (preferred), or sectioned tissue

          -  Participants with measurable disease per RECIST v1.1

        Additional Inclusion Criteria for Participants in Each Indication-Specific
        Exploration/Expansion Cohort of Phase 1b:

          -  NSCLC Cohorts (CIT-Naïve): Participants with histologically confirmed incurable,
             advanced NSCLC not previously treated with anti-PD−L1/PD-1 and/or with anti-CTLA−4
             (investigational or approved), for whom a clinical trial of an investigational agent
             in combination with an anti-PD−L1/PD-1 antibody is considered an acceptable treatment
             option (if CIT [including anti-PD−L1/PD-1 agents] is approved as treatment for NSCLC
             by local regulatory authorities).

          -  NSCLC Cohort (CIT-Treated): Participants with histologically confirmed incurable,
             advanced NSCLC previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4
             (investigational or approved)

          -  Triple negative breast cancer (TNBC) Cohort (CIT-Naïve): Participants with
             histologically confirmed incurable, advanced estrogen receptor (ER)-negative,
             progesterone receptor-negative, and human epidermal growth factor receptor 2
             (HER2)-negative adenocarcinoma of the breast (triple-negative) not previously treated
             with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)

          -  Colorectal cancer (CRC) Cohort (CIT-Naïve): Participants with histologically confirmed
             incurable, advanced adenocarcinoma of the colon or rectum not previously treated with
             anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)

          -  Head and neck squamous cell carcinoma (HNSCC) Cohort (CIT-Naïve): Participants with
             histologically confirmed inoperable, locally advanced or metastatic, recurrent, or
             persistent HNSCC (oral cavity, oropharynx, hypopharnyx, or larynx) not amenable to
             curative therapy not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4
             (investigational or approved)

          -  Urothelial carcinoma (UC) Cohort (CIT-Naïve): Participants with histologically
             confirmed incurable, advanced transitional cell carcinoma of the urothelium including
             renal pelvis, ureters, urinary bladder, and urethra, not previously treated with
             anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved), for whom a
             clinical trial of an investigational agent in combination with an anti-PD−L1 antibody
             is considered an acceptable treatment option, if CIT (including anti-PD−L1/PD-1
             agents) is approved as treatment for UC by local regulatory authorities

          -  UC Cohort (CIT-Treated): Participants with histologically confirmed incurable advanced
             transitional cell carcinoma of the urothelium (including renal pelvis, ureters,
             urinary bladder, and urethra) previously treated with anti-PD-L1/PD-1 with or without
             anti-CTLA-4 (investigational or approved)

          -  Renal cell carcinoma (RCC) Cohort (CIT-Naïve): Participants with histologically
             confirmed incurable, advanced RCC with component of clear cell histology and/or
             component of sarcomatoid histology not previously treated with anti-PD-L1/PD-1 and/or
             anti-CTLA-4 (investigational or approved)

          -  Melanoma Cohort (CIT-Naïve in metastatic setting): Participants with histologically
             confirmed incurable, advanced melanoma not previously treated with anti-PD-L1/PD-1
             and/or anti-CTLA-4 (investigational or approved) in the metastatic setting

          -  Melanoma Cohort (CIT-Treated): Participants with histologically confirmed incurable,
             advanced melanoma previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4
             (investigational or approved)

        Additional Inclusion Criteria for Participants in the Serial-Biopsy Expansion Cohort of
        Phase 1b:

          -  Participants must have one of the locally advanced or metastatic solid tumor types
             specified in the protocol.

          -  Participants must have accessible lesion(s) that permit a total of two to three
             biopsies (pretreatment and on-treatment) or one biopsy (on-treatment, if archival
             tissue can be submitted in place of a pre-treatment biopsy) without unacceptable risk
             of a significant procedural complication. RECIST lesions should not be biopsied.

        Exclusion Criteria:

          -  Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse

          -  Major surgical procedure within 28 days prior to Cycle 1, Day 1, or anticipation of
             need for a major surgical procedure during the course of the study

          -  Any other diseases, metabolic dysfunction, physical examination finding, and/or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or may render the participant at high risk from
             treatment complications

          -  Previous splenectomy

          -  Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative
             severe combined immunodeficiency [SCID]) or combined T- and B-cell immunodeficiencies
             (e.g., T- and B-negative SCID, Wiskott Aldrich syndrome, ataxia telangiectasia, common
             variable immunodeficiency)

          -  Any medical condition or abnormality in clinical laboratory tests that, in the
             investigator's judgment, precludes the participant's safe participation in and
             completion of the study Cancer-Specific Exclusion Criteria

          -  Any anti-cancer therapy, whether investigational or approved, including chemotherapy,
             hormonal therapy, and/or radiotherapy, within 3 weeks prior to initiation of study
             treatment, with the exceptions as mentioned in the protocol

          -  Eligibility based on prior treatment with CIT depends on the mechanistic class of the
             drug and the cohort for which the participant is being considered, as described below.
             In addition, all criteria pertaining to adverse events attributed to prior cancer
             therapies must be met

        All Cohorts (Dose-Escalation in Phase 1a and Dose-Escalation, Backfill, and Expansion in
        Phase 1b):

          -  Prior neoantigen-specific or whole-tumor cancer vaccines are not allowed, with the
             exception as specified in protocol

          -  Prior treatment with cytokines is allowed provided that at least 6 weeks or 5
             half-lives of the drug, whichever is shorter, have elapsed between the last dose and
             the proposed Cycle 1, Day 1

          -  Prior treatment with immune checkpoint inhibitors, immunomodulatory monoclonal
             antibody (mAbs), and/or mAb-derived therapies is allowed provided that at least 6
             weeks (Phase 1a) or 3 weeks (Phase 1b) have elapsed between the last dose and the
             proposed Cycle 1, Day 1, with the exceptions as specified in protocol Phase Ib
             Dose-Exploration/Expansion Group Only Cohorts

          -  In the CIT-Naïve expansion cohort in Phase Ib, prior treatment with anti-PD-L1/PD-1
             and/or anti-CTLA-4 (investigational or approved), is not allowed.

          -  In the melanoma CIT-naïve expansion cohort in Phase Ib, prior treatment with anti-PD-
             L1/PD-1 and/or anti-CTLA-4 (investigational or approved) in the metastatic, is not
             allowed.

          -  Prior treatment with immunomodulators, including toll-like receptor (TLR) agonists,
             inhibitors of indoleamine 2,3-dioxygenase (IDO)/ tryptophan-2,3-dioxygenase (TDO), or
             agonists of OX40, is allowed provided that at least 5 half-lives of the drug or a
             minimum of 3 weeks have elapsed between the last dose of the prior treatment and the
             proposed Cycle 1, Day 1, with the exception as specified in protocol

          -  Any history of an immune-related Grade 4 adverse event attributed to prior CIT (other
             than endocrinopathy managed with replacement therapy or asymptomatic elevation of
             serum amylase or lipase)

          -  Any history of an immune-related Grade 3 adverse event attributed to prior CIT (other
             than hypothyroidism managed with replacement therapy) that resulted in permanent
             discontinuation of the prior immunotherapeutic agent and/or occurred less than or
             equal to (<=) 6 months prior to Cycle 1 Day 1

          -  Adverse events from prior anti-cancer therapy that have not resolved to Grade <=1
             except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy

          -  All immune-related adverse events related to prior CIT (other than endocrinopathy
             managed with replacement therapy or stable vitiligo) must have resolved completely to
             baseline

          -  Primary central nervous system (CNS) malignancy, untreated CNS metastases, or active
             CNS metastases (progressing or requiring corticosteroids for symptomatic control)

          -  Leptomeningeal disease

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures

          -  Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1,
             with the exception of those with a negligible risk of metastasis or death

          -  Uncontrolled hypercalcemia

          -  Participant has 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 screening

        Treatment-Specific Exclusion Criteria:

          -  History of autoimmune disease with caveats as specified in protocol

          -  Treatment with monoamine oxidase inhibitors (MAOIs) within 3 weeks prior to Cycle 1,
             Day 1

          -  Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1,
             Day 1

          -  History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or
             evidence of active pneumonitis on screening chest computed tomography (CT) scan

          -  Positive test for human immunodeficiency virus (HIV) infection

          -  Active hepatitis B, hepatitis C

          -  Known active or latent tuberculosis infection

          -  Severe infections within 4 weeks prior to Cycle 1, Day 1

          -  Recent infections not meeting the criteria for severe infections within 2 weeks prior
             to Cycle 1, Day 1

          -  Prior allogeneic bone marrow transplantation or prior solid organ transplantation

          -  Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
             anticipation that such a live attenuated vaccine will be required during the study

          -  Known hypersensitivity to the active substance or to any of the excipients in the
             vaccine

          -  Phase 1b and crossover only: History of severe allergic, anaphylactic, or other
             hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins;
             Known hypersensitivity to Chinese Hamster Ovary (CHO)-cell products; Allergy or
             hypersensitivity to components of the atezolizumab formulation
      
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 (DLTs)
Time Frame:Phase 1a: Days 1 to 14 / Phase 1b: Days 1 to 21
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Plasma Concentration of (R)-N,N,N-Trimethyl-2,3-Dioleyloxy-1-Propanaminium Chloride (DOTMA)
Time Frame:Pre-infusion (0 hour [hr]) until treatment discontinuation (up to approximately 3 years)
Safety Issue:
Description:
Measure:Plasma Concentration of Ribonucleic Acid (RNA)
Time Frame:Pre-infusion (0 hr) until treatment discontinuation (up to approximately 3 years)
Safety Issue:
Description:
Measure:Serum Concentration of Atezolizumab
Time Frame:Pre-infusion (0 hr) until 2 months post treatment discontinuation (up to approximately 3 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Induction of Antigen-Specific T-Cell Responses in Peripheral Blood
Time Frame:Pre-infusion (0 hr) until treatment discontinuation (up to approximately 3 years)
Safety Issue:
Description:
Measure:Immune-Related Cytokine Levels
Time Frame:Pre-infusion (0 hr) until treatment discontinuation (up to approximately 3 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria for Solid Tumors Version 1.1 (RECIST v1.1)
Time Frame:Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years)
Safety Issue:
Description:
Measure:Duration of Response (DoR) According to RECIST v1.1
Time Frame:From first occurrence of a documented objective response (CR or PR) until disease progression or death due to any cause, whichever occurs first (up to approximately 3 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response of CR or PR According to Immune-Modified RECIST
Time Frame:Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years)
Safety Issue:
Description:
Measure:DoR According to Immune-Modified RECIST
Time Frame:From first occurrence of a documented objective response (CR or PR) until disease progression or death due to any cause, whichever occurs first (up to approximately 3 years)
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS) According to RECIST v1.1
Time Frame:Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years)
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to approximately 3 years)
Safety Issue:
Description:
Measure:Percentage of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab
Time Frame:Pre-infusion (0 hr) until 2 months post treatment discontinuation (up to approximately 3 years)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genentech, Inc.

Trial Keywords

  • Cancer vaccine
  • Neoantigen
  • Personalized
  • Atezolizumab
  • Vaccine
  • Immunotherapy
  • Anti-PDL1
  • Checkpoint Inhibitor
  • Personalized vaccine

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