Clinical Trials /

A Study of RO7121661 and RO7247669 Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus

NCT04785820

Description:

This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of RO7121661 and RO7247669, compared with nivolumab, in patients with advanced or metastatic esophageal squamous-cell carcinoma (ESCC) refractory or intolerant to fluoropyrimidine- or taxane- and platinum-based regimen.

Related Conditions:
  • Esophageal Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of RO7121661 and RO7247669 Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus
  • Official Title: A 3-Arm, Randomized, Blinded, Active-Controlled, Phase II Study of RO7121661, a PD1-TIM3 Bispecific Antibody and RO7247669, a PD1-LAG3 Bispecific Antibody, Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus

Clinical Trial IDs

  • ORG STUDY ID: BP42772
  • SECONDARY ID: 2020-004606-60
  • NCT ID: NCT04785820

Conditions

  • Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
RO7121661RG7769, PD1-TIM3 BsAbRO7121661
RO7247669RG6139, PD1-LAG3 BsAbRO7247669
NivolumabOpdivo®Nivolumab

Purpose

This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of RO7121661 and RO7247669, compared with nivolumab, in patients with advanced or metastatic esophageal squamous-cell carcinoma (ESCC) refractory or intolerant to fluoropyrimidine- or taxane- and platinum-based regimen.

Trial Arms

NameTypeDescriptionInterventions
RO7121661Experimental
  • RO7121661
RO7247669Experimental
  • RO7247669
NivolumabActive Comparator
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Major lesion was histologically confirmed esophageal squamous-cell carcinoma (ESCC)

          -  Patients who have previously received 1 line of treatment with either a
             fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen in
             non-curative intention prior to randomization; or patients who received treatment with
             a fluoropyrimidine-/taxane- and platinum-based regimen in curative intention and had
             recurrence within 24 weeks after the last dose of the treatment

          -  Radiologically measurable disease according to RECIST v1.1. Previously irradiated
             lesions should not be counted as target lesions unless clearly progressed after the
             radiotherapy

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  A life expectancy of at least (≥)12 weeks

          -  Tissue samples must be provided for analysis of anti-programmed death ligand-1 (PD-L1)
             tumor positivity

          -  Adverse events from any prior radiotherapy, chemotherapy, or surgical procedure must
             have resolved to Grade ≤1, except alopecia (any grade), vitiligo, endocrinopathy
             managed with replacement therapy, and Grade 2 peripheral neuropathy

          -  Adequate cardiovascular, hematological, liver, and renal function

          -  Serum albumin ≥25 grams per liter (g/L),

          -  For participants not receiving therapeutic anticoagulation: prothrombin time (PT) and
             activated partial thromboplastin time ≤1.5 times (×) the upper limit of normal (ULN);
             for participants receiving therapeutic anticoagulation: stable anticoagulant regimen

          -  A female participant is eligible to participate if she is not pregnant, not
             breastfeeding, not a woman of childbearing potential (WOCBP), or a WOCBP who agrees to
             remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
             during the treatment period and for at least 5 months after the final dose of study
             drug and have a negative pregnancy test (blood) within the 7 days prior to
             randomization.

          -  A male participant must remain abstinent (refrain from heterosexual intercourse) or
             use contraceptive measures such as a condom plus an additional contraceptive method
             and refrain from donating sperm during the treatment period and for at least 5 months
             after the final dose of study drug

        Exclusion Criteria:

          -  Pregnancy, lactation, or breastfeeding

          -  Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab,
             including but not limited to, hypersensitivity to Chinese hamster ovary cell products
             or other recombinant human or humanized antibodies

          -  Patients with significant malnutrition. Patients whose nutrition has been well
             controlled for ≥28 days prior to randomization may be enrolled

          -  Evidence of complete esophageal obstruction not amenable to treatment

          -  Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent
             organs (aorta or tracheobronchial tree)

          -  Symptomatic central nervous system (CNS) metastases

          -  Spinal cord compression not definitively treated with surgery and/or radiation or
             without evidence that disease has been clinically stable for ≥14 days prior to
             randomization

          -  Active or history of carcinomatous meningitis/leptomeningeal disease

          -  Asymptomatic CNS primary tumors or metastases if they have requirement for steroids or
             enzyme inducing anticonvulsants in the last 28 days prior to randomization

          -  Uncontrolled tumor-related pain. Participants requiring pain medication must be on a
             stable regimen at study entry

          -  Active second malignancy (with some exceptions)

          -  Evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results, including diabetes
             mellitus, history of relevant pulmonary disorders, known autoimmune diseases or immune
             deficiency, or other diseases with ongoing fibrosis (such as scleroderma, pulmonary
             fibrosis, emphysema, neurofibromatosis, palmar/plantar fibromatosis, etc.).

          -  Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed
             consent

          -  Significant cardiovascular/cerebrovascular disease within 6 months prior to
             randomization

          -  Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but
             not limited to tuberculosis [TB] and typical mycobacterial disease), parasitic, or
             other infection (excluding fungal infections of nail beds) or any major episode of
             infection requiring treatment with intravenous (IV) antibiotics or hospitalization
             (relating to the completion of the course of antibiotics, except if for tumor fever)
             within 28 days prior to randomization

          -  Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis,
             and inherited liver disease.

          -  Major surgical procedure or significant traumatic injury (excluding biopsies) within
             28 days prior to randomization, or anticipation of the need for major surgery during
             the course of the study

          -  Any other diseases, metabolic dysfunction, physical examination finding, 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 render the participant at high risk from treatment
             complications

          -  Dementia or altered mental status that would prohibit informed consent

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (expected to occur once monthly or more frequently)

          -  Active or history of autoimmune disease or immune deficiency

          -  Positive human immunodeficiency virus (HIV) test at screening

          -  Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core
             antibody (HBcAb) test at screening

          -  Positive hepatitis C virus (HCV) antibody test at screening

          -  Prior cancer therapy with any immunomodulatory agents including checkpoint inhibitors
             (CPIs; such as anti-PDL1/PD1, anti-CTLA-4, anti-LAG3, anti-TIM3)

          -  Vaccination with live vaccines within 28 days prior to randomization, or anticipation
             that a live attenuated vaccine will be required during the study

          -  Treatment with therapeutic oral or IV antibiotics within 14 days prior to
             randomization

          -  Concurrent therapy with any other investigational drug (defined as treatment for which
             there is currently no regulatory authority approved indication) 28 days or 5
             half-lives of the drug (whichever is shorter) prior to randomization

          -  Treatment with immune-modulating and immune suppressive agents/medication 5 half-lives
             or 28 days (whichever is shorter) prior to randomization

          -  Regular immunosuppressive therapy (i.e., for organ transplantation, chronic
             rheumatologic disease)

          -  Radiotherapy within the last 28 days before start of study drug treatment is not
             allowed, with the exception of limited palliative radiotherapy

          -  Prior treatment with adoptive cell therapies, such as chimeric antigen receptor T
             cells (CAR-T) therapies
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival, Defined as the Time from Randomization to Death from Any Cause
Time Frame:Up to 3 years, 4 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of Participants with Adverse Events, Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0)
Time Frame:Up to 3 years, 4 months
Safety Issue:
Description:
Measure:Objective Response Rate (ORR), Defined as the Percentage of Participants with a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
Time Frame:Up to 3 years, 4 months
Safety Issue:
Description:
Measure:Disease Control Rate (DCR), Defined as the Percentage of Participants with an Objective Response or Stable Disease According to RECIST v1.1
Time Frame:Up to 3 years, 4 months
Safety Issue:
Description:
Measure:Duration of Response for Participants with ORR, Defined as the Time from the First Occurrence of a Documented Objective Response to Disease Progression According to RECIST v1.1 or Death from any Cause, Whichever Occurs First
Time Frame:Up to 3 years, 4 months
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS), Defined as the Time from Randomization to the First Occurrence of Progression as Determined According to RECIST v1.1 or Death from any Cause, Whichever Occurs First
Time Frame:Up to 3 years, 4 months
Safety Issue:
Description:
Measure:Percentage of Participants Reporting Clinically Meaningful Improvement in Global Health Status/Quality of Life (GHS/QoL), and Emotional and Social Functioning, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC QLQ-C30
Time Frame:Baseline (Day 1 of Cycle 1) and Day 1 of Cycles 4, 7, and 10 (each cycle is 14 days); then every 3 months until treatment discontinuation; and every 3 months during the first year of post-treatment follow-up (up to 3 years)
Safety Issue:
Description:EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30
Measure:Percentage of Participants Reporting a Clinically Meaningful Improvement in GHS/QoL, and Emotional and Social Functioning, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC IL97 Questionnaire
Time Frame:Baseline (Cycle 1 Day 1) and Day 1 of Cycles 2, 3, 5, 6, 8, and 9 (each cycle is 14 days)
Safety Issue:
Description:EORTC IL97 = European Organisation for Research and Treatment of Cancer - Item Library 97
Measure:Percentage of Participants Reporting a Clinically Meaningful Improvement in Dysphagia, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC QLQ-OES18
Time Frame:Baseline (Cycle 1 Day 1) and Day 1 of each subsequent treatment cycle (each cycle is 14 days) until treatment discontinuation; and every 3 months during the first year of post-treatment follow-up (up to 3 years)
Safety Issue:
Description:EORTC QLQ-OES18 = European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire for Esophageal Cancer
Measure:Serum Concentrations of RO7121661, RO7247669, and Nivolumab
Time Frame:Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)
Safety Issue:
Description:
Measure:Area Under the Time-Serum Concentration Curve (AUC) of RO7121661, RO7247669, and Nivolumab
Time Frame:Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)
Safety Issue:
Description:
Measure:Maximum Serum Concentrations of RO7121661, RO7247669, and Nivolumab
Time Frame:Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)
Safety Issue:
Description:
Measure:Total Clearance of RO7121661, RO7247669, and Nivolumab
Time Frame:Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)
Safety Issue:
Description:
Measure:Volume of Distribution at Steady State of RO7121661, RO7247669, and Nivolumab
Time Frame:Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)
Safety Issue:
Description:
Measure:Terminal Half-Life of RO7121661, RO7247669, and Nivolumab
Time Frame:Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years)
Safety Issue:
Description:
Measure:Number of Participants with Anti-Drug Antibodies (ADAs) to RO7121661, RO7247669, or Nivolumab at Baseline and During the Study
Time Frame:Predose at Baseline (Day 1 of Cycle 1) and on Day 1 of Cycles 2, 3, 4, 5, and 7, and then every 3 cycles thereafter (each cycle is 14 days); and at treatment discontinuation (up to 2 years)
Safety Issue:
Description:
Measure:Change from Baseline in the Number of T-cell Subsets by Phenotype and Activation Status (CD4/CD8 HLA-DR+Ki67+) in the Peripheral Blood
Time Frame:Predose at Baseline (Day 1 of Cycle 1) and on Day 1 of Cycles 2, 3, 5, and 7, and then every 3 cycles thereafter (each cycle is 14 days); and at treatment discontinuation (up to 2 years)
Safety Issue:
Description:
Measure:Change from Baseline in the Number of CD8+ T-cells Infiltrating the Tumor Microenvironment
Time Frame:Baseline and Day 1 of Cycle 3 (each cycle is 14 days)
Safety Issue:
Description:
Measure:Change from Baseline in the Number of CD8+ T-cells Proliferating (CD8+Ki67+) in the Tumor Microenvironment
Time Frame:Baseline and Day 1 of Cycle 3 (each cycle is 14 days)
Safety Issue:
Description:
Measure:Baseline PDL1, CD8+PD1+, CD8+TIM3+, and CD8+LAG3+ Expression in the Tumor Microenvironment
Time Frame:At Baseline
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

March 8, 2021