Metastatic Colorectal Cancer
Conditions
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.
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. Patients with metastatic RAS/RAF WT colorectal cancer who have previously had a radiological response to EGFR inhibitors i.e. Cetuximab or Panitumumab, either combined with chemotherapy or as single agents, but subsequently experienced progression of their disease will be eligible for the study. They will consent to the study ideally within 3 months having progressed/ become refractory to EGFR blockable and undergo a mandatory baseline biopsy within this time period. Patients will receive Nivolumab and Relatlimab every 4 weeks and will start on study treatment as soon as possible after the baseline biopsy. 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. Patients 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.
Interventions
DRUGNivolumab
Immunotherapy
Sponsors
Royal Marsden NHS Foundation Trust
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged ≥18 years 2. 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 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 4. Estimated life expectancy of at least 3 months at the time of informed consent per Investigator assessment 5. 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 6. Negative serum or urine pregnancy test at screening for women of childbearing potential\*\* 7. 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. 8. 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 9. Resolved acute effects of prior therapy to baseline severity or ≤Grade 1 except for AEs not constituting a safety risk by investigator judgement 10. Signed and dated informed consent 11. 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 12. 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
Patients are not eligible for the trial if any of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease Control Rate (DCR) | 6 months from treatment initiation |
Secondary
| Measure | Time frame |
|---|---|
| NCI CTCAE version 5.0 toxicity | within 30 days of the last dose of study treatment |
| Disease Control Rate (DCR) | 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 |
| Overall survival | time from registration to death from any cause at 6 months, 12 months and 24 months |
| Duration of disease control | 6, 12 and 24 months |
Countries
United Kingdom
Outcome results
None listed