Clinical Trials /

iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer

NCT03867799

Description:

This is a single-arm, single centre open-label, phase II interventional clinical trial of combination immunotherapy with Nivolumab and Relatlimab in mCRC.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer
  • Official Title: Immunotherapy Sequencing in COlon and REctal Cancer

Clinical Trial IDs

  • ORG STUDY ID: CCR4938
  • NCT ID: NCT03867799

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
NivolumabRelatlimabNivolumab and Relatlimab

Purpose

This is a single-arm, single centre open-label, phase II interventional clinical trial of combination immunotherapy with Nivolumab and Relatlimab in mCRC.

Detailed Description

      This is a single-arm, single centre open-label, phase II interventional clinical trial of
      combination immunotherapy with Nivolumab and Relatlimab in mCRC.

      Participants with metastatic RAS/RAF WT colorectal cancer who have previously had a
      radiological response to standard first line therapy with FOLFIRI and Cetuximab but
      subsequently experienced progression of their disease will be eligible for the study. They
      will consent to the study within 4 weeks of having progressed/ become refractory to FOLFIRI
      and Cetuximab and undergo a mandatory baseline biopsy within this time period.

      Participants will receive Nivolumab and Relatlimab every 4 weeks. After starting on the study
      drugs, there will be a mandatory 'on-treatment' biopsy at day 21 ± 3 days. Response
      assessments in the form of either CT or MRI scans will take place every 8 weeks throughout
      the study for the 12 months and every 12 weeks from 12 months onwards. Participants will
      continue on the study until progressive disease (PD) is confirmed by RECIST 1.1 or when
      maximum duration of treatment of 24 months has been reached.

      There will be the possibility of 'treating beyond progression' if participants are deriving
      clinical benefit from treatment to encompass the possibility of pseudoprogression. At PD
      participants will undergo a further biopsy. The investigators envisage enrolling a total of
      25 participants and the investigators anticipate 30 months as a feasible time frame for
      accrual.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab and RelatlimabExperimentalNivolumab 480mg and Relatlimab 160mg will be administered intravenously every 4 weeks
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female patients aged ≥18 years

          -  Patients with histologically confirmed advanced/metastatic RAS/RAF wild type colon or
             rectal adenocarcinoma who had a prior radiological response to first line treatment
             with FOLFIRI and Cetuximab but have subsequently progressed/ become refractory to this
             treatment based on physician judgment

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

          -  Estimated life expectancy of at least 3 months at the time of informed consent per
             Investigator assessment

          -  Adequate organ functioning including haematological, renal, liver and cardiac function

          -  Negative serum or urine pregnancy test at screening for women of childbearing
             potential and use of highly effective contraception for both male and female patients
             throughout the study

          -  Patient must consent and be eligible to undergo mandatory baseline and sequential
             biopsies

          -  Presence of measurable disease as defined by RECIST v 1.1 criteria for response
             assessment

        Exclusion Criteria:

          -  Systemic therapy within 4 weeks prior to the planned administration of the first study
             treatment dose

          -  Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry.
             Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has
             been completed 48 hours prior to study entry and there is at least one measurable
             lesion that has not been irradiated.

          -  Previous exposure to immune checkpoint inhibitors or immune co-stimulatory drugs

          -  Uncontrolled or significant cardiovascular disease including including patients with a
             history of myocarditis, regardless of aetiology

          -  Known severe hypersensitivity reactions (Grade ≥ 3 NCI CTCAE v 5.0) to monoclonal
             antibodies or related compounds or any of their components

          -  Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal,
             inhaled, topical steroids, or local steroid injection (e.g., intra-articular
             injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone
             or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT
             scan premedication)

          -  Known history of testing positive test for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS)

          -  Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV
             antibody tested positive)

          -  Active, known or suspected autoimmune disease that might deteriorate when receiving an
             immuno-stimulatory agent. Patients with type I diabetes mellitis, hypothyroidism only
             requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or
             alopecia) not requiring systemic treatment, or conditions not expected to recur in the
             absence of an external trigger are permitted to enroll

          -  Patients with a history of interstitial lung disease or radiological evidence of
             pulmonary fibrosis

          -  Pregnancy or lactation

          -  Vaccination within 4 weeks of the first dose of study drugs and while on trial is
             prohibited except for administration of inactivated vaccines
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease Control Rate (DCR)
Time Frame:6 months from treatment initiation
Safety Issue:
Description:

Secondary Outcome Measures

Measure:NCI CTCAE version 5.0 toxicity
Time Frame:within 30 days of the last dose of study treatment
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:12 and 24 months
Safety Issue:
Description:
Measure:Duration of disease control
Time Frame:6, 12 and 24 months
Safety Issue:
Description:
Measure:Best Objective Response Rate
Time Frame:6, 12 and 24 months
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:Time from registration to progression (radiological or clinical) or death at 6 months, 12 months and 24 months
Safety Issue:
Description:
Measure:Overall survival
Time Frame:time from registration to death from any cause at 6 months, 12 months and 24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Royal Marsden NHS Foundation Trust

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