Nous-209 Genetic Vaccine for the Treatment of Microsatellite Unstable Solid Tumors

Ref: Protocol Version 9.1 05 December 2024. Both Frame Shift Peptide (FSP) neoantigen-encoding genetic vaccines are administered intramuscularly using 1 prime with the GAd20-209-FSP and 3 boosts with MVA-209-FSP in combination with Keytruda®, the licensed programmed death receptor-1 (PD-1)-blocking antibody pembrolizumab, in adult subjects with unresectable or metastatic Mismatch Repair Deficient (dMMR) or MSI-H colorectal cancer (CRC), gastric, or G-E junction tumors. In Phase I, GAd20-209-FSP prime will be administered on the day of 2nd pembrolizumab infusion (week 4); MVA-209-FSP boosts will be administered on the day of 3rd, 4th and 5th pembrolizumab infusion (weeks 7 and 10 and 13). In Phase II, GAd20-209-FSP prime will be administered on the same day as the 1st pembrolizumab infusion (day 1, week 1); MVA-209-FSP boosts will be administered on the day of the 2nd, 3rd, and 4th pembrolizumab infusion (Weeks 4, 7, and 10). The study is composed of a Phase I divided in two parts and a Phase II, as described below : Phase I: * Cohort A - Dose escalation Cohort of Nous-209 vaccine plus pembrolizumab combination therapy in adult subjects with unresectable or metastatic deficient mismatch repair (dMMR) or MSI-H CRC, gastric, or gastro-esophageal junction (G-E junction) tumors; * Cohort B - Expansion Cohort at Recommended Phase 2 Dose (RP2D) of Nous-209 vaccine plus pembrolizumab combination therapy in adult subjects with unresectable or metastatic dMMR or MSI-H CRC, gastric, or G-E junction tumors. Part 2 - Extended Follow-up from week 27 to week 110. Phase I (Cohorts A and B): The Sponsor estimates that the trial will require approximately 24 months from the time the first subject signs the informed consent until the last subject's last visit at week 26 (Main Study); and approximately 42 months until last subject's last visit at week 110 (Extended follow up). Phase II: Expansion at RP2D of Nous-209 vaccine plus Keytruda® (pembrolizumab) combination therapy in adult subjects in the following study population: * Cohort C (Phase II) - Subjects with locally advanced unresectable or metastatic, microsatellite instability high (MSI-H) or dMMR CRC who are eligible for anti-PD-1 1st line of treatment. Subjects will be randomized with an allocation ratio 2:1 to Nous-209 vaccine plus pembrolizumab combination therapy versus pembrolizumab monotherapy. * Cohort D (Phase II) - Subjects with locally advanced unresectable or metastatic, microsatellite instability high (MSI-H) or dMMR CRC who have had radiographic progression (PD) after having a best response of stable disease (SD) or better on/after anti-PD1 treatment will receive Nous-209 vaccine plus pembrolizumab. Treatment duration per patient is expected to last to approximately 2 years (completion of 35 administrations of pembrolizumab over approximately 103 weeks). Enrollment in Phase I and II is now terminated.