Ignite Creation Date:
2024-05-06 @ 1:31 PM
Last Modification Date:
2024-10-26 @ 1:15 PM
Study NCT ID:
NCT04041310
Status:
RECRUITING
Last Update Posted:
2024-07-08
First Post:
2019-07-21
Brief Title:
Nous-209 Genetic Vaccine for the Treatment of Microsatellite Unstable Solid Tumors
Sponsor:
Nouscom SRL
Organization:
Nouscom SRL
Study Overview
Official Title:
A Phase III Multicenter Open-Label Study of Nous-209 Genetic Vaccine for the Treatment of Microsatellite Unstable Solid Tumors
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Ref Protocol v90 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 primeboost 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 v90 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 subjects last visit at week 26 Main Study and approximately 42 months until last subjects 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 21 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 onafter 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 is now terminated and in Phase II is ongoing
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 subjects last visit at week 26 Main Study and approximately 42 months until last subjects 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 21 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 onafter 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 is now terminated and in Phase II is ongoing
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| IND 018954 | OTHER | None | None |
| 2021-002823-40 | EUDRACT_NUMBER | None | None |
| MK-3475-E58 | OTHER | None | None |
| KEYNOTE-E58 | OTHER | Merck Sharp Dohme LLC | None |