In this study, the efficacy of botensilimab and balstilimab in mismatch repair deficient (dMMR) and mismatch repair proficient (pMMR) tumors will be assessed.
The NEOASIS study is an adaptive, pan-cancer, single-center, open-label, basket study assessing the efficacy of botensilimab and balstilimab in patients with resectable dMMR and pMMR solid tumors of various origins. Patients will be included in baskets according to tumor type and mismatch repair (MMR) status and will receive 2 cycles of immunotherapy followed by surgery. The trial will commence with two safety run-in cohorts: one for patients with dMMR tumors and one for patients with pMMR tumors that will run in parallel. These safety run-in cohort will be used to assess safety and feasibility of pre-operative botensilimab + balstilimab. Data from the safety run-in cohorts will be used to determine the dosing and scheduling to be used in the MMR-specific cohorts of the main study. Safety will be assessed according to dose limiting toxicities. In the run-in cohorts, the first five patients will receive botensilimab 25mg intravenously (IV) on Day1 plus balstilimab 450mg IV on Day1 and Day22. Patients 6-10 will receive botensilimab 50mg IV on Day1 plus balstilimab 450mg IV on Day1 and Day22 followed by surgery 8 weeks after registration. After full accrual of the run-in cohorts, MMR-specific baskets including a "other cancers" basket will start accrual with the optimal dose and schedule as determined in the safety run-in followed by surgery 8 weeks after registration. The MMR-specific baskets are designed with a Simon's 2 stage design in which first 8 patients will be included, if in the first 8 patients \>2 Major pathological responses are reported (defined as ≤10% residual viable tumor) accrual of 10 more patients will continue for a total of 18 patients per basket.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
92
Anti cytotoxic T-lymphocyte associated protein-4 (anti-CTLA4)
Anti programmed cell death protein-1 (anti-PD1)
The Netherlands Cancer Institute
Amsterdam, North Holland, Netherlands
RECRUITINGMajor pathological response rate
Percentage of patients in which a major pathologic response (MPR) is reported, defined as \<10% residual viable tumor (RVT) in the resection specimen.
Time frame: Week 8
Pathological response rates
Pathologic complete response (pCR) defined as no RVT in the primary tumor and locoregional lymph nodes; partial pathologic response (≤50% RVT) and no pathologic response (\>50% RVT)
Time frame: Week 8
Event free survival
Event-free survival defined as time from registration to the date of disease progression, local, regional or distant recurrence, occurrence of a second primary cancer or death from any cause.
Time frame: 3 years
Disease free survival
Disease free survival defined as the time from surgery to disease recurrence during follow-up which consists of either local or regional recurrence, metastatic disease or disease-related death.
Time frame: 3 years
Overall survival
Overall survival defined as time from registration until death from any cause.
Time frame: 5 years
Radiological response
Radiological response measured according to RECIST 1.1
Time frame: Week 8
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