Clinical Trials /

A Study to Evaluate Safety and Anti-Tumor Activity of RO7284755 Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors

NCT04303858

Description:

This is an entry-into-human study and will assess the effects of RO7284755 as a single agent and in combination with atezolizumab in adult participants with solid tumors considered responsive to checkpoint inhibition blockade. The maximum duration in the study for each participant will be up to 28 months.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Safety and Anti-Tumor Activity of RO7284755 Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors
  • Official Title: An Open-Label, Multicenter, Randomized, Dose-Escalation and Extension, Phase IA/IB Study to Evaluate Safety and Anti-Tumor Activity of RO7284755, A PD-1 Targeted IL-2 Variant (IL-2V) Immunocytokine, Alone or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BP41628
  • SECONDARY ID: 2019-004022-25
  • NCT ID: NCT04303858

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
RO7284755RO7284755 as a Single Agent
AtezolizumabTecentriqRO7284755 as a Single Agent and/or with Atezolizumab

Purpose

This is an entry-into-human study and will assess the effects of RO7284755 as a single agent and in combination with atezolizumab in adult participants with solid tumors considered responsive to checkpoint inhibition blockade. The maximum duration in the study for each participant will be up to 28 months.

Detailed Description

      The study consists of three parts: dose-escalation of RO7284755 as a single agent (Part 1),
      dose-escalation of RO7284755 in combination with atezolizumab (Part 2), and extension of
      RO7284755 as a single agent and/or in combination with atezolizumab (Part 3).
    

Trial Arms

NameTypeDescriptionInterventions
RO7284755 as a Single AgentExperimentalPart 1: Dose-escalation of RO7284755 as a single agent. RO7284755 will be either an intravenous administration (IV) or subcutaneous administration (SC) in multiple-ascending doses.
  • RO7284755
RO7284755 in Combination with AtezolizumabExperimentalPart 2: Dose-escalation of RO7284755 in combination with atezolizumab.
  • RO7284755
  • Atezolizumab
RO7284755 as a Single Agent and/or with AtezolizumabExperimentalPart 3: Extension of RO7284755 as a single agent and/or in combination with atezolizumab.
  • RO7284755
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Locally advanced/unresectable or metastatic disease

          -  Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version
             1.1 (RECIST v1.1)

          -  Eastern Cooperative Oncology Group Performance Status 0 to 1

          -  Life expectancy of >=12 weeks

          -  Consent to provide an archival tumor tissue sample

          -  Adequate cardiovascular, hematological, coagulative, hepatic and renal function

        Exclusion Criteria:

          -  Rapid disease progression or suspected hyperprogression or threat to vital organs or
             critical anatomical sites requiring urgent alternative medical intervention

          -  Known active central nervous system (CNS) metastases

          -  History of treated asymptomatic CNS metastases

          -  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 before Cycle1 Day 1 (C1D1)

          -  Active or history of carcinomatous meningitis/leptomeningeal disease

          -  Uncontrolled tumor-related pain or symptomatic hypercalcemia

          -  Concurrent second malignancy

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results

          -  Episode of significant cardiovascular/cerebrovascular acute disease within 28 days
             before study treatment administration

          -  Active or uncontrolled infections

          -  Known HIV infection

          -  Hepatitis B virus (HBV) or hepatitis C virus infection

          -  Adverse events related to any prior radiotherapy, chemotherapy, targeted therapy, CPI
             therapy or surgical procedure must have resolved to Grade <=1, except alopecia Grade 2
             peripheral neuropathy, and hypothyroidism and/or hypopituitarism on a stable dosage of
             hormone replacement therapy

          -  Participants with bilateral pleural effusion

          -  Major surgery or significant traumatic injury < 28 days before study treatment
             administration or anticipation of the need for major surgery during study treatment

          -  Known allergy or hypersensitivity to any component of the formulations of the IMPs to
             be administered, including but not limited to hypersensitivity to Chinese hamster
             ovary cell products or other recombinant or humanized antibodies

          -  History of severe allergic anaphylactic reactions to chimeric, human or humanized
             antibodies, or fusion proteins
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Adverse Events in Part 1 and Part 2
Time Frame:From randomization until end of Part 1 and Part 2 (up to approximately 1.5 months)
Safety Issue:
Description:An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Secondary Outcome Measures

Measure:Investigator Assessed Objective Response Rate according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Parts 1 and 2
Time Frame:From randomization until end of Part 1 and Part 2 (up to approximately 1.5 months)
Safety Issue:
Description:ORR was defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).
Measure:Percentage of Participants with Adverse Events in Part 3
Time Frame:From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measure:Disease Control Rate in Part 3
Time Frame:From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
Safety Issue:
Description:The disease control rate was defined as proportion of participants being either responder or in 'stable disease' (SD). To classify a response as SD, measurements will have to be classified as stable (according to RECIST v1.1) at least once at a minimum of 4 weeks after study entry.
Measure:Duration of Response in Part 3
Time Frame:From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
Safety Issue:
Description:Duration of response will be calculated for 'responder' participants (i.e. best [confirmed] overall response of CR or PR) and will be defined as the time from first occurrence of a documented response until the time of documented disease progression or death (death within 30 days from last study treatment) from any cause, whichever occurs first.
Measure:Progression-free survival (PFS) in Part 3
Time Frame:From start of extension phase until disease progression, drug discontinuation, withdrawal or death (up to approximately 26 months)
Safety Issue:
Description:Progression-free survival was defined as the time from first dose of study treatment to the first occurrence of documented disease progression (based on RECIST 1.1 Investigator's assessment) or death from any cause, whichever occurs first.
Measure:Change from Baseline in Antidrug Antibody (ADA) to RO7284755
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Percentage of Partcipants with ADAs to RO7284755
Time Frame:Up to 28 months
Safety Issue:
Description:
Measure:Area Under the Curve (AUC) for RO7284755
Time Frame:Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Safety Issue:
Description:
Measure:Minimum Concentration (Cmin) for RO7284755
Time Frame:Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Safety Issue:
Description:
Measure:Maximum Concentration (Cmax) for RO7284755
Time Frame:Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Safety Issue:
Description:
Measure:Clearance (CL) for RO7284755
Time Frame:Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Safety Issue:
Description:
Measure:Volume of Distribution at Steady-State Conditions (Vss) for RO7284755
Time Frame:Predose, C1 Days 1, 2, 3, 5, 8, 9, 10, 12, 15, 16, 17, and 19; C2 Days 1, 2, 8, 9, 10, 12, 15, and 16; C3 Days 1, 2, 3, and 8; C4 Days 1 and 2; C5 Days1, 2, and 8; and days 1 and 2 for any subsequent cycles (Up to 28 months)
Safety Issue:
Description:
Measure:Percentage of Immune and Tumor Cells with Positive Programmed Cell Death-1 (PD-1) and Programmed Cell Death-Ligand 1 (PD-L1) Expression in the Tumor Microenvironment (TME)
Time Frame:Baseline
Safety Issue:
Description:
Measure:Percentage of Immune Cells with CD8+ PD1+ and CD8+ PD1+ TCF7+ Expression
Time Frame:Baseline
Safety Issue:
Description:
Measure:Blood Tumor Mutational Burden
Time Frame:Baseline
Safety Issue:
Description:Blood tumor mutational burden is defined as the number of genetic mutations per megabase (1,000,000 bases).
Measure:Change from Baseline in Percentage of Immune Cell Subsets
Time Frame:Baseline to End of Treatment (up to approximately 28 months)
Safety Issue:
Description:Immune cells include NK, CD8, and Treg cells
Measure:Change from Baseline in Percentage of Immune Markers
Time Frame:Baseline to End of Treatment (up to approximately 28 months)
Safety Issue:
Description:Immune markers include PD-1, PD-L1, sCD25, cytokines, etc...

Details

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

Last Updated

June 3, 2020