Abstract 169TiP
Background
Patients with microsatellite instability (MSI) solid tumors are equisitely sensitive to immune-checkpoint inhibitors (ICIs). The pharmacokinetics data as well as early efficacy data have shown that low dose- ICIs (LD-ICIs) may have similar efficacy to standard dose in MSI solid tumors. While standard dose pembrolizumab as well as the combination of nivolumab and ipililumab are effective therapeutic options in advanced colorectal cancers (mCRC), it may not be feasible in a majority of patients in low income countries (LICs) and lower middle income countries (LMICs). With this background, the current study aims to evaluate the efficacy of LD-Nivolumab in mCRC.
Trial Design
The CLOUD study is planned as a single-arm, open-label, prospective, phase 2 superiority study. Adults aged >= 18 years with adequate end-organ function and Eastern Cooperative Oncology Group performance status (PS) 0-1 diagnosed with treatment naïve unresectable or metastatic colorectal adenocarcinoma (patients could have received previous adjuvant chemotherapy for colorectal cancer if the earlier treatment had been completed at least 6 months before enrolement) with MSI status (on Polymerase Chain reaction or Next Generation Sequencing) or deficient mismatch repair (dMMR) protein status on biopsy will be considered for enrolment. Accrued patients will receive nivolumab 40 mg IV every 3 weekly for 6 months and then 6 weekly for next 6 months (maximum of 12 months or till disease progression, whichever is earlier). The study is planned in two stages. The null hypothesis is that the true progression free survival is 35% at 12 months with chemotherapy, which will be tested against a one-sided alternative. In the first stage, 20 patients will be accrued, and if there are 7 or fewer patients who are progression free at 12 months in these 20 patients, the study will be stopped. Otherwise, 27 additional patients will be accrued for a total of 47 patients. The null hypothesis will be rejected if 21 or more have progressed within 12 months in the entire cohort. This design yields a type I error rate of 0.1 and power of 90 when the progression free survival at 12 months is 55%. Assuming a loss to follow up or attrition rate of 10%, the total sample size of the study 52 patients.
Clinical trial identification
CTRI/2024/01/061681, Registered on: 22/01/2024.
Legal entity responsible for the study
Tata Memorial Hospital.
Funding
TMC Research Administration Council (TRAC), Tata Memorial Centre.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
7P - ACOX2 disturbs the stability of MRE11-RAD50-NBS1 complex and shapes activated immune tumor microenvironment in clear cell renal cell carcinoma
Presenter: Shiqi Ye
Session: Poster Display session
Resources:
Abstract
9P - CXCR6+PD-1- Tissue Resident memory T cells are associated with poor prognosis in patients with metastatic colorectal cancer
Presenter: Emilien Laloy
Session: Poster Display session
Resources:
Abstract
10P - Tumor-infiltrating lymphocytes and tertiary lymphoid structures in oral cavity squamous cell carcinoma in non-smokers and non-drinkers: Predict clinical outcome
Presenter: Israa Laklouk
Session: Poster Display session
Resources:
Abstract
11P - Tumor-infiltrating lymphocytes on routine H&E staining with automated quantification predict outcomes in resectable non-small cell lung cancer
Presenter: Guus Heuvel
Session: Poster Display session
Resources:
Abstract
12P - Epithelial-mesenchymal transition facilitates response to AXL/PD-1 inhibition in relapsed mesothelioma
Presenter: Essa Baitei
Session: Poster Display session
Resources:
Abstract
14P - Integrated genomic analysis of whole genomes to derive a biomarker of durable response to immunotherapy in melanoma
Presenter: Irene Lobon
Session: Poster Display session
Resources:
Abstract
15P - Verteporfin might potentiate the effects of anti-PD-1 therapy in melanoma-bearing mice model
Presenter: Szonja Kovács
Session: Poster Display session
Resources:
Abstract
16P - Immune checkpoint blockade and HLA-related epistasis in melanoma: Genetic determinants of response and toxicity
Presenter: Martin Little
Session: Poster Display session
Resources:
Abstract
17P - Identification PD-L1-associated lncRNA biomarkers for immunoregulation in ovarian cancer
Presenter: Hee Jung Kim
Session: Poster Display session
Resources:
Abstract
19P - Genetic profiling of early triple-negative breast cancer patients with an indication for neoadjuvant pembrolizumab
Presenter: Bogdan Popescu
Session: Poster Display session
Resources:
Abstract