iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer

• Status: Recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Royal Marsden NHS Foundation Trust
• Treatments: Nivolumab

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 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 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