Nouscom announced positive results from a Phase 2 trial evaluating NOUS-209 in combination with pembrolizumab for patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer who are refractory to anti-PD-1 therapy. The results were presented at the European Society for Medical Oncology (ESMO) Annual Meeting in Berlin.
Clinical Trial Results
The Phase 2 study enrolled 20 evaluable patients with deficient mismatch repair (dMMR)/MSI-H metastatic colorectal cancer who had progressed on prior anti-PD-1 treatment. Among the participants, 77% had received prior single-agent anti-PD-1 therapy, while 23% received combination therapy with anti-CTLA-4. The median number of prior treatment lines was 2, ranging from 1 to 7.
The primary endpoint was objective response rate (ORR), with secondary endpoints including progression-free survival (PFS) and safety. The trial achieved an ORR of 15% with three partial responses, while the disease control rate reached 70%, comprising 11 patients with stable disease and 6 with progressive disease. Median progression-free survival was 6.4 months.
Immune Response and Retreatment Outcomes
The treatment demonstrated robust immune activation in 80% of patients. Seven patients (32%) were retreated with NOUS-209 at 6 months, with notable outcomes: 86% remained in stable disease and 14% achieved a partial response. The patient with partial response showed induction of a strong, durable, and polytopic T cell immune response with a desired effector memory phenotype, correlating with clinical response.
"These clinical data are very encouraging. NOUS-209 combined with pembrolizumab has demonstrated meaningful disease control and immune activation in patients who have exhausted anti-PD-1 therapy," said Dr. Sven Gogov, Chief Medical Officer of Nouscom.
Addressing Unmet Medical Need
MSI-H metastatic colorectal cancer represents a biologically distinct subtype characterized by mismatch repair deficiency. While anti-PD-1 therapies with or without anti-CTLA-4 are approved as first-line treatment, over 50% of patients do not respond to initial therapy, and many responding patients eventually develop resistance and progress.
"There remains a high unmet need for effective therapies that can overcome anti-PD-1 resistance and provide durable disease control. These data are promising in this difficult-to-treat patient population given the modest clinical benefit of approved options in the same setting," said Javier Ros, MD PhD, from Vall d'Hebron University Hospital.
NOUS-209 Mechanism and Development
NOUS-209 is an investigational off-the-shelf cancer immunotherapy targeting tumors with mismatch repair deficiency and high microsatellite instability. The treatment comprises two proprietary viral vectors designed to deliver 209 shared frameshift peptide (FSP) neoantigens, which are unique to cancerous cells and absent in healthy cells. This approach trains the immune system to recognize and attack cancerous and pre-cancerous cells.
The safety profile remained favorable throughout the study, with no emerging safety findings reported. The treatment maintained its established safety characteristics while demonstrating clinical activity in this challenging patient population.
Future Development Plans
Dr. Marina Udier, Chief Executive Officer of Nouscom, expressed enthusiasm about the broader clinical dataset: "We are excited by the overall positive clinical dataset emerging from the completed clinical trials of NOUS-209, not only in MSI-H mCRC patients but also the Phase 1b/2 results in Lynch Syndrome carriers that were presented earlier this year at AACR. These results support our commitment to advancing NOUS-209 into a registration-enabling study for cancer interception in Lynch Syndrome carriers."
The company is also developing NOUS-209 monotherapy for cancer interception in Lynch Syndrome carriers, with a registration-enabling Phase 2/3 study in preparation following positive Type B and C FDA meetings. Additionally, NOUS-209 is being studied in a randomized Phase 2 study in combination with pembrolizumab for first-line treatment of advanced dMMR and/or MSI-H metastatic colorectal cancer.
