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
5 other identifiers
interventional
115
6 countries
46
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2019
Longer than P75 for phase_1
46 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 21, 2019
CompletedFirst Posted
Study publicly available on registry
August 1, 2019
CompletedStudy Start
First participant enrolled
October 21, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 30, 2026
February 13, 2026
February 1, 2026
7 years
July 21, 2019
February 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Toxicity (DLT assessment), in Phase I, Cohort A
Toxicity analyzed within 28-days from the administration of the prime vaccination with GAd20-209-FSP
Within 28 days
Safety and Tolerability, in Phase I, Cohort A and B.
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.
Up to 110 weeks
Overall Response Rate (ORR) at any time during the study, in Phase II (Cohort C and D).
Assessed using RECIST v1.1
18 months
Secondary Outcomes (2)
Immunogenicity (T cell responses against vaccine FSPs) in Phase I, Cohorts A and B
Through study completion, an average of 2 years
Safety and tolerability (local and systemic AEs), in Phase II (Cohort C and D)
Up to 24 months
Other Outcomes (7)
Clinical: Overall Response Rate (ORR), in Phase I, Cohort A and B
Phase I Main Study and Extended follow-up. Up to 110 weeks
Clinical: Disease Control Rate (DCR), in Phase I, Cohort A and B
Phase I Main Study and Extended follow-up. Up to 110 weeks
Clinical: Time to Tumor Response (TTR), Phase I Main Study and Extended follow-up.
Phase I Main Study and Extended follow-up. Up to 110 weeks.
- +4 more other outcomes
Study Arms (4)
Cohort A - Dose-escalation
EXPERIMENTALPhase 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
EXPERIMENTALPhase 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 C - Expansion cohort Phase II
EXPERIMENTALPhase 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
EXPERIMENTALPhase 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.
Interventions
MVA-209-FSP IP, RP2D
GAd20-209-FSP IP, RP2D
anti-PD-1 checkpoint inhibitor (200 mg; Q3W)
Eligibility Criteria
You may qualify if:
- In order to be eligible, the subject must:
- Have the ability to comprehend and willingness to provide written informed consent (ICF) for the study.
- Have previously proven microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) status (confirmatory testing is not required);
- dMMR/MSI Testing: Patients are eligible to the combined treatment based on previous diagnosis for dMMR/MSI status. dMMR/MSI status diagnosis should be performed locally by IHC or NGS or PCR based tests that are certified per local requirements (Hara et al. 2018; Boland et al. 1998) CDx ™, 2017.
- Patients with locally advanced unresectable or metastatic, microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) CRC who are eligible for anti-PD-1 1st line of treatment. Patients may have received prior adjuvant chemotherapy for CRC as long as it was completed at least 6 months prior to Study Day 1 .
- Be ≥18 years of age on day of signing informed consent.
- Have a life expectancy of at least 6 months.
- Have a performance status of 0 - 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
- Have resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 2 or less (except alopecia). If subject received major surgery or radiation therapy they must have recovered from the toxicity and/or complications from the intervention.
- Have adequate organ function as defined in the following tables (Table 1. Adequate Organ Function Laboratory Values ). Specimens must be collected within 10 days prior to the start of study treatment. If any hematological or chemistry values are outside the specified range during the initial screening, rescreening process may be conducted to reassess and ensure compliance with the adequate organ function criteria as outlined in Table 1.
- Not be previously treated with a (licensed or experimental) anti-PD-1 or anti-PD-L1 checkpoint inhibitor.
- If participating in translational research \[see Section 7.0.6 Translational research (only selected sites)\], agree to have a biopsy at baseline from a lesion that can be biopsied with an acceptable clinical risk (as judged by the Investigator in discussion with the interventional radiologist or endoscopist). An older (not older than 6 months) FFPE specimen from locations not radiated prior to biopsy can be accepted. Furthermore, optionally agree to have another biopsy taken on-treatment if not representing an unacceptable clinical risk and/or if technically feasible as judged by the Investigator in discussion with the interventional radiologist or endoscopist.
- Have measurable disease per RECIST version 1.1.
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Females: not be pregnant (see Appendix 7: Contraceptive Guidance and Pregnancy Testing), not breastfeed, and must have at least one of the following conditions that apply:
- +36 more criteria
You may not qualify if:
- The patient must be excluded from participating in if he/she:
- Has a diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (have no evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any worsening of neurologic symptoms with respect to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to pembrolizumab.
- Is expected to require any form of systemic or localized antineoplastic therapy while on study other than the study drugs.
- Phase IIa and Cohort C only: Had prior adjuvant treatment with an anti-PD1, or PD-L1 or PD-L2 agent or an antibody targeting other immunoregulatory receptors or mechanisms.
- Cohort D only:
- discontinued prior therapy with a checkpoint inhibitor due to Grade 3, or higher, treatment-related toxicities.
- Had prior allogenic tissue or solid organ transplant.
- Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
- Has known history of HIV (HIV1/2 antibodies). HIV-infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
- Participants on ART must have a CD4+ T-cell count \>350 cells/mm3 at time of screening
- Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening.
- Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to study entry (Day 1)
- HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
- Had prior radiotherapy within 2 weeks of enrollment, or within 4 weeks of enrollment in the case of radiation to central nervous system (CNS), which requires ≥4-week washout. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- +28 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Nouscom SRLlead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (46)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
City of Hope Comprehensive Cancer Center
Irvine, California, 92618, United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90089, United States
USC Norris Comprehensive Cancer Center
Newport Beach, California, 92663, United States
Mt. Sinai
Miami Beach, Florida, 33140, United States
Boca Raton Clinical Research
Plantation, Florida, 33322, United States
Goshen Center for Cancer Care
Goshen, Indiana, 46526, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
Washington University School of Medicine, Division of Oncology
St Louis, Missouri, 63110, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14203, United States
NYU Langone Medical Center
New York, New York, 10016, United States
Weill Cornell Medicine / New York-Presbyterian Hospital
New York, New York, 10021, United States
MD Anderson Cancer Center (MDACC)
Houston, Texas, 77030, United States
Cliniques Universitaires Saint-Luc - Centre du Cancer
Brussels, 1200, Belgium
Centre Hospitalier de l'Ardenne - Libramont - Clinique du Sein
Libramont, 6800, Belgium
CHU de Liège
Liège, 4000, Belgium
Mount Sinai Hospital
Toronto, M5G 2M9, Canada
Princess Margaret Cancer Center
Toronto, M5G 2M9, Canada
Aorn Sg Moscati
Avellino, 83100, Italy
Candiolo cancer Center,FPO IRCCS
Candiolo, 10060, Italy
IRCCS Ospedale San Raffaele
Milan, 20132, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133, Italy
Ospedale Niguarda
Milan, 20162, Italy
AOUS Policlinico Le Scotte
Siena, 53100, Italy
Hospital Universitario de A Coruna
A Coruña, 15006, Spain
Hospital Del Mar
Barcelona, 08003, Spain
Hospital Universitari Dexeus
Barcelona, 08028, Spain
Hospital Vall d'Hebron
Barcelona, 08035, Spain
Institut Catala d'Oncologia Hospitalet
Barcelona, 08908, Spain
Hospital Clinic de Barcelona
Barcelona, Spain
Hospital Universitario Reina Sofia
Córdoba, 14004, Spain
Hospital Universitario Virgen de las Nieves
Granada, 18014, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Clinica Universidad de Navarra
Madrid, 28027, Spain
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Universitario HM Sanchinarro
Madrid, Spain
Clinica Universidad de Navarra
Pamplona, 31008, Spain
Complejo Asistencial de Salamanca
Salamanca, 37007, Spain
Hospital Universitario Marques de Valdecilla
Santander, Spain
Hospital Clínico Universitario de Santiago de Compostela
Santiago de Compostela, 15706, Spain
Hospital General Universitario de Valencia
Valencia, 46014, Spain
University Clinical Hospital Valencia
Valencia, Spain
Hospital Universitario Miguel Servet
Zaragoza, 50009, Spain
University College London Hospitals NHS Foundation Trust Cancer Clinical Trials Unit
London, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Sven Gogov, MD
Nouscom SRL
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 21, 2019
First Posted
August 1, 2019
Study Start
October 21, 2019
Primary Completion (Estimated)
October 30, 2026
Study Completion (Estimated)
October 30, 2026
Last Updated
February 13, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share