NCT04041310

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

A Phase I/II, Multicenter, Open-Label Study of Nous-209 Genetic Vaccine for the Treatment of Microsatellite Unstable Solid Tumors

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 115 (estimated)
• Sponsor: Nouscom SRL · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Ref: Protocol Version 9.1 05 December 2024. NOUS-209-01 is a multicenter, open-label, multiple cohorts, clinical study, designed to evaluate safety, tolerability, and immunogenicity, and to detect any preliminary evidence of anti-tumor activity of Nous-209 genetic polyvalent 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. Nous-209 is based on a heterologous prime/boost regimen composed of the Great Ape Adenovirus GAd20-209-FSP used for priming and Modified Vaccinia virus Ankara MVA-209-FSP used for boosting. The Phase I portion of the study is a first-in-human (FIH) clinical study with a primary objective to elucidate the safety and tolerability of Nous-209 in addition to establishing the recommended Phase 2 dose (RP2D), whereas the Phase II was introduced to assess efficacy as the primary objective.

Detailed description

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.

Conditions

• Solid Tumor, Adult

Interventions

Type	Name	Description
BIOLOGICAL	GAd-209-FSP low dose	GAd20-209-FSP IP, low dose
BIOLOGICAL	MVA-209-FSP low dose	MVA-209-FSP IP, low dose
BIOLOGICAL	GAd-209-FSP high dose	GAd20-209-FSP IP, high dose
BIOLOGICAL	MVA-209-FSP high dose	MVA-209-FSP IP, high dose
BIOLOGICAL	GAd20-209-FSP, RP2D	GAd20-209-FSP IP, RP2D
BIOLOGICAL	MVA-209-FSP, RP2D	MVA-209-FSP IP, RP2D
DRUG	KEYTRUDA®	anti-PD-1 checkpoint inhibitor (200 mg; Q3W)

Timeline

• Start date: 2019-10-21
• Primary completion: 2026-10-30
• Completion: 2026-10-30
• First posted: 2019-08-01
• Last updated: 2026-02-13

Locations

46 sites across 6 countries: United States, Belgium, Canada, Italy, Spain, United Kingdom

Regulatory

• FDA-regulated drug study