Nouscom, a clinical-stage immuno-oncology company, has announced the completion of patient enrollment in its randomized Phase 2 study evaluating NOUS-209 in combination with pembrolizumab for first-line treatment of Deficient Mismatch Repair/Microsatellite Instable (dMMR/MSI) unresectable and metastatic colorectal cancer (mCRC). The trial, which enrolled 69 patients, aims to determine if NOUS-209 immunotherapy improves clinical efficacy beyond the current standard of care.
The primary efficacy endpoint, Objective Response Rate (ORR) based on RECIST1.1, is anticipated in mid-2025. This multi-center trial is being conducted across the US and Europe and includes a 2:1 randomized cohort receiving NOUS-209 plus pembrolizumab versus pembrolizumab alone, as well as a single-arm cohort of MSI mCRC patients refractory to prior anti-PD1 therapies receiving NOUS-209 plus pembrolizumab.
Mechanism of Action and Prior Clinical Data
NOUS-209 is an off-the-shelf immunotherapy designed to activate the immune system by targeting MSI tumor-specific neoantigens. These neoantigens arise from defects in DNA mismatch repair genes (dMMR), common in MSI tumors. The immunotherapy encodes 209 neoantigens shared across sporadic and hereditary MSI tumors, aiming to generate CD8 and CD4 T cell responses.
Data from a Phase 1b trial of NOUS-209 plus pembrolizumab in dMMR/MSI gastrointestinal (GI) tumors demonstrated a favorable safety profile and encouraging results. The combination induced strong and long-lasting CD8 and CD4 T cell responses in 90% of patients. Expansion of intratumoral T cells was observed post-NOUS-209 immunotherapy in patients with deep and durable clinical responses, indicating that neoantigen-specific CD8 T cells induced by NOUS-209 successfully infiltrate the tumor.
Management Commentary
"The completion of enrollment of our randomized multi-country Phase 2 trial in MSI metastatic mCRC patients is a major milestone for Nouscom," said Dr. Marina Udier, CEO of Nouscom. "With important data readouts expected in 2025, we are getting closer to answering the key question of whether NOUS-209 immunotherapy meaningfully improves clinical efficacy above and beyond the current standard of care in MSI mCRC."
Dr. Sven Gogov, Chief Medical Officer of Nouscom, added, "Colorectal cancer continues to be a leading cause of death, highlighting a clear unmet medical need. This trial, taken with the positive data from our ongoing Phase 1b/2 trial in Lynch Syndrome carriers, continues to support the transformative potential of NOUS-209 immunotherapy from the interception of cancer at the pre-malignant stage through to treating advanced metastatic disease."
About MSI Tumors and Lynch Syndrome
Microsatellite instable (MSI) tumors are characterized by high mutation rates due to defects in the DNA mismatch repair (MMR) system. MSI metastatic CRC represents approximately 4-5% of all metastatic CRC cases and is associated with increased sensitivity to certain immunotherapies. MSI is also observed in other cancers, including endometrial and gastric cancers.
Lynch Syndrome (LS) is a hereditary condition caused by mutations in DNA mismatch repair genes, leading to MSI tumors. LS carriers face a 50-80% lifetime risk of colorectal cancer and a 40-60% risk of endometrial cancer.
