iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer

NCT03867799 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: CCR4938
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate (DCR)

  6 months from treatment initiation

Secondary Outcomes (6)

• NCI CTCAE version 5.0 toxicity

  within 30 days of the last dose of study treatment

• Disease Control Rate (DCR)

  12 and 24 months

• Duration of disease control

  6, 12 and 24 months

• Best Objective Response Rate

  6, 12 and 24 months

• Progression Free Survival

  Time from registration to progression (radiological or clinical) or death at 6 months, 12 months and 24 months

Study Arms (1)

Nivolumab and Relatlimab

EXPERIMENTAL

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

Drug: Nivolumab

Interventions

Nivolumab DRUG

Immunotherapy

Also known as: Relatlimab

Nivolumab and Relatlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 EGFR blockade as a single agent or in combination with chemotherapy but have subsequently progressed/ become refractory to this treatment based on physician judgment. Patients should not have received any other systemic anti-cancer therapy between the end of treatment with EGFR inhibitors as a single agents or in combination with chemotherapy and screening for the iSCORE study
• 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 as defined by the following:
• i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (stable off any growth factor within 4 weeks prior to first study drug administration) ii. Platelet count ≥ 100 × 109/L (Transfusion to achieve this level is not permitted within 2 weeks of first study drug administration) iii. Haemoglobin ≥ 8.5 g/dL (Transfusion to achieve this level is not permitted within 2 weeks of first study drug administration) iv. Creatinine \< 1.5 X ULN or creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula) v. AST and ALT levels ≤ 3 × ULN vi. Lipase and amylase \< 1.5 ULN vii. Total bilirubin level ≤ 1.5 ULN (except patients with Gilbert's Syndrome who must have a normal direct bilirubin) viii. Normal thyroid function or on stable hormone supplementation per investigator assessment ix. Albumin \>28 g/dL x. LVEF assessment with documented LVEF ≥ 50% by TTE within 6 months from first study drug administration
• Negative serum or urine pregnancy test at screening for women of childbearing potential\*\*
• Highly effective contraception for both male and female patients throughout the study and for at least 165 days for women 225 days for males after the last treatment administration if the risk of conception exists. Please refer to Section 9.15 - Pregnancy reporting for details of acceptable and unacceptable methods of contraception.
• Patient must consent and be eligible to undergo mandatory baseline and sequential biopsies; in such case as a specimen cannot be obtained at acceptable clinical risk as judged by the Investigator then patients may still be included in the study. Patients must not be anti-coagulated at the time of biopsy or on aspirin/clopidogrel for 7 days pre-biopsy
• Resolved acute effects of prior therapy to baseline severity or ≤Grade 1 except for AEs not constituting a safety risk by investigator judgement
• Signed and dated informed consent
• Patients willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other procedures. Prisoners and patients who are involuntarily incarcerated are excluded
• Presence of measurable disease as defined by RECIST v 1.1 criteria for response assessment \*\* Defined as a pre-menopausal female capable of becoming pregnant. This includes women on oral, injectable or mechanical contraception

You may not qualify if:

• 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
• Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation
• Previous exposure to immune checkpoint inhibitors or immune co-stimulatory drugs such as but not limited to anti-CTLA-4, anti-PD-1, anti-PDL1, anti-PD-2, anti-KIR, anti-CD137, anti-LAG-3, anti-OX40 antibodies or IDO or CXCR2 targeted agents
• Known severe hypersensitivity reactions (Grade ≥ 3 NCI CTCAE v 5.0) to monoclonal antibodies or related compounds or any of their components (e.g. history of severe hypersensitivity reactions to drugs formulated with polysorbate 80), any history of anaphylaxis or uncontrolled asthma (defined a 3 or more features of partially controlled asthma)
• 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)
• Active infection requiring systemic therapy
• Any active malignancy, with the exception of adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer or other locally curable cancers including superficial bladder cancer, carcinoma in situ of the prostate, cervix or breast
• Significant acute or chronic infections including, among others:
• 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)
• All patients with brain metastases, except those meeting the following criteria:
• Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment
• No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
• Patients must be either off steroids or on a stable or decreasing dose of \<10mg daily prednisone (or equivalent)

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead

Study Sites (1)

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab; relatlimab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2019
• First Posted: March 8, 2019
• Study Start: March 27, 2019
• Primary Completion: October 21, 2022
• Study Completion: September 1, 2024
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)