Clinical Trial Finder

Comments

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.
Anti PD-1 + anti-LAG-3 monoclonal antibody BMS – 986016 (Relatlimab)
No prior anti PD-1 allowed Similar to other trials, other locations, with Relatlimab.

Inclusion 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 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

Exclusion Criteria

Exclusion Criteria

Patients are not eligible for the trial if any of the exclusion criteria below are met:

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 480 msec
History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association [NYHA] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc )
Cardiovascular disease-related requirement for daily supplemental oxygen
History of two or more MIs OR two or more coronary revascularization procedures
Patients with history of myocarditis, regardless of aetiology
Troponin T (TnT) or I (TnI) > 2 × institutional ULN. Patients with TnT or TnI levels between > 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤1 x ULN. If TnT or TnI levels are >1 to 2 × ULN within 24 hours, the patient may undergo a cardiac evaluation and be considered for treatment based on the discretion of the PI. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are < 2 x ULN, the patient may undergo a cardiac evaluation and be considered for treatment, based on the discretion of the CI Patients with a history of interstitial lung disease or radiological evidence of pulmonary fibrosis Persisting toxicity related to prior therapy (NCI CTCAE v. 5.0 Grade > 1) except alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable
Pregnancy or lactation (females of childbearing potential must have a negative pregnancy test within 3 days prior to treatment initiation and every month during treatment
Known alcohol or drug abuse
Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Any psychiatric condition that would prohibit the understanding or rendering of informed consent
Vaccination within 4 weeks of the first dose of study drugs and while on trial is prohibited except for administration of inactivated vaccines
A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent