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

Phase 1

Active, not recruiting

• Conditions: Solid Tumor, Adult
• Interventions: Biological: GAd-209-FSP high dose; Biological: GAd-209-FSP low dose; Biological: GAd20-209-FSP, RP2D; Biological: MVA-209-FSP high dose; Biological: MVA-209-FSP low dose; Biological: MVA-209-FSP, RP2D; Drug: KEYTRUDA®

• Registration Number: NCT04041310
• Lead Sponsor: Nouscom SRL

Brief Summary

Ref: Protocol v9.0, dated 7Nov2023. 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 v9.0, dated 7Nov2023. 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 in week 2 and at the time of the 2nd and 3rd pembrolizumab infusions (weeks 4 and 7).

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.

Phase II (Cohorts C and D): Participation duration per subject is expected to last up to 18 months in Cohort C and up to 12 months in Cohort D.

Subjects who do not progress might stay in extended follow-up for up to approximately 2 years (106 weeks or completion of 35 administrations of pembrolizumab).

Enrollment in Phase I and II is now terminated.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations
|
Related News

Study Timeline

• Study First Submitted: 2019-07-21
• Study First Submitted QC: 2019-07-31
• Study First Posted: 2019-08-01
• Study Start: 2019-10-21
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-20
• Primary Completion: 2025-04-30
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 115

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort B - Expansion Cohort Phase I	GAd-209-FSP high dose	Phase I. Part 1. Expansion cohort at RP2D. Subjects treated with RP2D dose of GAd20-209-FSP prime and MVA-209-FSP boosts, in combination with pembrolizumab. Phase I. Part 2 - Extended Follow-up from week 27 to week 110. Subjects with unresectable or metastatic dMMR or MSI-H CRC, gastric, or G-E junction tumors.
Cohort B - Expansion Cohort Phase I	MVA-209-FSP high dose	Phase I. Part 1. Expansion cohort at RP2D. Subjects treated with RP2D dose of GAd20-209-FSP prime and MVA-209-FSP boosts, in combination with pembrolizumab. Phase I. Part 2 - Extended Follow-up from week 27 to week 110. Subjects with unresectable or metastatic dMMR or MSI-H CRC, gastric, or G-E junction tumors.
Cohort A - Dose-escalation	GAd-209-FSP low dose	Phase I. Part 1. Dose escalation cohort. Subjects treated with low dose or with high dose of GAd20-209-FSP prime and MVA-209-FSP boosts to define the RP2D, in combination with pembrolizumab. Phase I. Part 2 - Extended Follow-up from week 27 to week 110. Subjects with unresectable or metastatic deficient mismatch repair (dMMR) or MSI-H CRC, gastric, or gastro-esophageal junction (G-E junction) tumors.
Cohort A - Dose-escalation	MVA-209-FSP low dose	Phase I. Part 1. Dose escalation cohort. Subjects treated with low dose or with high dose of GAd20-209-FSP prime and MVA-209-FSP boosts to define the RP2D, in combination with pembrolizumab. Phase I. Part 2 - Extended Follow-up from week 27 to week 110. Subjects with unresectable or metastatic deficient mismatch repair (dMMR) or MSI-H CRC, gastric, or gastro-esophageal junction (G-E junction) tumors.
Cohort C - Expansion cohort Phase II	GAd20-209-FSP, RP2D	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 Keytruda® (pembrolizumab) combination therapy versus pembrolizumab monotherapy.
Cohort C - Expansion cohort Phase II	MVA-209-FSP, RP2D	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 Keytruda® (pembrolizumab) combination therapy versus pembrolizumab monotherapy.
Cohort C - Expansion cohort Phase II	KEYTRUDA®	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 Keytruda® (pembrolizumab) combination therapy versus pembrolizumab monotherapy.
Cohort D - Expansion cohort Phase II	GAd20-209-FSP, RP2D	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. Nous-209 vaccine plus Keytruda® (pembrolizumab) combination therapy.
Cohort D - Expansion cohort Phase II	MVA-209-FSP, RP2D	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. Nous-209 vaccine plus Keytruda® (pembrolizumab) combination therapy.
Cohort A - Dose-escalation	KEYTRUDA®	Phase I. Part 1. Dose escalation cohort. Subjects treated with low dose or with high dose of GAd20-209-FSP prime and MVA-209-FSP boosts to define the RP2D, in combination with pembrolizumab. Phase I. Part 2 - Extended Follow-up from week 27 to week 110. 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 Phase I	KEYTRUDA®	Phase I. Part 1. Expansion cohort at RP2D. Subjects treated with RP2D dose of GAd20-209-FSP prime and MVA-209-FSP boosts, in combination with pembrolizumab. Phase I. Part 2 - Extended Follow-up from week 27 to week 110. Subjects with unresectable or metastatic dMMR or MSI-H CRC, gastric, or G-E junction tumors.
Cohort D - Expansion cohort Phase II	KEYTRUDA®	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. Nous-209 vaccine plus Keytruda® (pembrolizumab) combination therapy.

Primary Outcome Measures

Name	Time	Method
Toxicity (DLT assessment), in Phase I, Cohort A	Within 28 days	Toxicity analyzed within 28-days from the administration of the prime vaccination with GAd20-209-FSP
Safety and Tolerability, in Phase I, Cohort A and B.	Up to 110 weeks	AEs as characterized by type, severity (graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v.5.0), timing, seriousness, and relationship to study treatments.
Overall Response Rate (ORR) at any time during the study, in Phase II (Cohort C and D).	18 months	Assessed using RECIST v1.1

Secondary Outcome Measures

Name	Time	Method
Immunogenicity (T cell responses against vaccine FSPs) in Phase I, Cohorts A and B	Through study completion, an average of 2 years	PBMC-derived T cell responses against vaccine FSPs, as measured by IFN-gamma ELISpot
Safety and tolerability (local and systemic AEs), in Phase II (Cohort C and D)	Up to 18 months	AEs as characterized by type, severity (graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v.5.0), timing, seriousness, and relationship to study treatments. Assessed by standard using RECIST v1.1 criteria at 6, 12 and 18 months.

Trial Locations

Locations (43)

Centre Hospitalier de l'Ardenne - Libramont - Clinique du Sein; 🇧🇪 Libramont, Belgium

CHU de Liège; 🇧🇪 Liège, Belgium

Mount Sinai Hospital; 🇨🇦 Toronto, Canada

Princess Margaret Cancer Center; 🇨🇦 Toronto, Canada

Aorn Sg Moscati; 🇮🇹 Avellino, Italy

Candiolo cancer Center,FPO IRCCS; 🇮🇹 Candiolo, Italy

IRCCS Ospedale San Raffaele; 🇮🇹 Milano, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

Ospedale Niguarda; 🇮🇹 Milano, Italy

AOUS Policlinico Le Scotte; 🇮🇹 Siena, Italy

Hospital Universitario de A Coruna; 🇪🇸 A Coruna, Spain

Hospital Del Mar; 🇪🇸 Barcelona, Spain

Hospital Universitari Dexeus; 🇪🇸 Barcelona, Spain

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Institut Catala d'Oncologia Hospitalet; 🇪🇸 Barcelona, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario Reina Sofia; 🇪🇸 Córdoba, Spain

Hospital Universitario Virgen de las Nieves; 🇪🇸 Granada, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Clinica Universidad de Navarra; 🇪🇸 Pamplona, Spain

Hospital Universitario Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

Complejo Asistencial de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Spain

Hospital Clínico Universitario de Santiago de Compostela; 🇪🇸 Santiago De Compostela, Spain

Hospital General Universitario de Valencia; 🇪🇸 Valencia, Spain

University Clinical Hospital Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

University College London Hospitals NHS Foundation Trust Cancer Clinical Trials Unit; 🇬🇧 London, United Kingdom

City of Hope Comprehensive Cancer Center; 🇺🇸 Irvine, California, United States

USC Norris Comprehensive Cancer Center; 🇺🇸 Newport Beach, California, United States

Mt. Sinai; 🇺🇸 Miami Beach, Florida, United States

Boca Raton Clinical Research; 🇺🇸 Plantation, Florida, United States

Goshen Center for Cancer Care; 🇺🇸 Goshen, Indiana, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Washington University School of Medicine, Division of Oncology; 🇺🇸 St Louis, Missouri, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

NYU Langone Medical Center; 🇺🇸 New York, New York, United States

Weill Cornell Medicine / New York-Presbyterian Hospital; 🇺🇸 New York, New York, United States

MD Anderson Cancer Center (MDACC); 🇺🇸 Houston, Texas, United States

Cliniques Universitaires Saint-Luc - Centre du Cancer; 🇧🇪 Bruxelles, Belgium