DMMR Colorectal Cancer

This is a multicenter, open-label, randomized (1:1) trial designed to evaluate whether ctDNA-guided interruption of immune-checkpoint inhibitor (ICI) therapy provides comparable survival to standard of care (SoC) continuous ICI therapy in patients with histologically confirmed advanced/metastatic non-small cell lung cancer (NSCLC), melanoma, microsatellite instability-high (MSI-High)/Deficient Mismatch Repair (dMMR) colorectal cancer (CRC), renal cell carcinoma (RCC) and other solid tumors. This study will be conducted in up to 100 sites.

This study will collect tumor specimens with correlated clinical and demographic data from patients who are undergoing a biopsy or similar procedure to obtain tumor tissue as a normal course of their medical management or diagnostic work-up for suspected or confirmed cancer.

This is a Phase II, single arm study looking at the rate of major clinical response and non-operative management in Stage II and III colon cancer after 18 weeks (up to 6 cycles) of neoadjuvant dostarlimab.

The RESET C2 trial aims to introduce organ sparing treatment or watch-and-wait (WW) to patients with localized deficient mismatch repair (dMMR) colon cancer through use of neoadjuvant pembrolizumab. Patients will be divided into four treatment arms based on their surgical and oncologic risks. Each arm provides different intensity neoadjuvant immunotherapy regimens. Patients with complete response at disease restaging procedures will be offered non-operative management, whereas those with non-complete response will proceed to surgery ± adjuvant chemotherapy as standard of care. A WW protocol with regular disease surveillance continues over survivorship. If there is recurrence, surgery and/or appropriate oncologic therapy will be offered determined by multi-disciplinary teams. This is a national, non-randomised, investigator-initiated trial including patients from 13 hospitals across Denmark. The rationale, design, and clinical response metrics are derived from the RESET C study (NCT05662527) showing efficacy, safety and feasibility of neoadjuvant pembrolizumab in this cohort.

This study aims to explore the optimal number of cycles of PD-1 monotherapy required at minimum, under the premise of ensuring pathological complete response (pCR) among patients with dMMR/MSI-H rectal cancer. Participants will receive preoperative monotherapy with PD-1 antibodies, with regular reassessments every 2 cycles. Surgical intervention will be performed if clinical complete response (cCR) is achieved. Researchers will compare the pathological complete response rates, adverse reactions, and three-year event-free survival rates across different treatment cycles.