AzTrials
AzTrials

Solid Tumor, AdultPhase 1/2NCT04041310

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

A Phase 1/2 study testing GAd-209-FSP low dose, MVA-209-FSP low dose and GAd-209-FSP high dose in people with Solid Tumor, Adult, run by Nouscom SRL at 46 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Adult
What is being tested?
GAd-209-FSP low dose, MVA-209-FSP low dose and GAd-209-FSP high dose
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
115 participants
Where
46 sitesin 6 countries
Study dates
21 Oct 2019to 30 Oct 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • Not a woman of childbearing potential (WOCBP) as defined in Appendix 7: Contraceptive Guidance and Pregnancy Testing OR
  • A WOCBP who agrees to use highly effective contraceptive methods as outlined in Appendix 7: Contraceptive Guidance and Pregnancy Testing during the treatment period and for at least 180 days after the last dose of study treatment and refrain from egg donation during this period.
  • Fertile male patients: agree to use a contraceptive as detailed in Appendix 7:
  • Contraceptive Guidance and Pregnancy Testing of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
  • 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 MSI-H/dMMR CRC who have had radiographic progression (PD) after having a best response of stable disease (SD) or better on/after anti-PD-1 treatment.
  • May have progressed on additional approved therapy.
  • 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 cancer therapies to Grade 2 or less (except alopecia). If patient received major surgery or radiation therapy they must have recovered from the toxicity and/or complications from the intervention.
  • Have adequate hematological and blood chemistry values for Phase II as indicated in Table 1. Adequate Organ Function Laboratory Values. The 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 adequate organ function criteria as outlined in Table 1.
  • 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:
  • Not a woman of childbearing potential (WOCBP) as defined in Appendix 7: Contraceptive Guidance and Pregnancy Testing OR
  • A WOCBP who agrees to use highly effective contraceptive methods as outlined in Appendix 7: Contraceptive Guidance and Pregnancy Testing during the treatment period and for at least 180 days after the last dose of study treatment and refrain from egg donation during this period.
  • Male patients: agree to use a contraceptive as detailed in Appendix 7: Contraceptive Guidance and Pregnancy Testing of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
  • Table 1: Adequate Organ Function Laboratory Values
  • Hematological
  • Absolute neutrophil count (ANC) ≥1500/µL
  • Platelets ≥100 000/µL
  • Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (1)
  • Renal Creatinine OR Measured or calculated creatinine (2) clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
  • Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
  • Coagulation [Optional]
  • International normalized ratio (INR) OR prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • ALT (SGPT)= alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)= aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR= glomerular filtration rate; ULN= upper limit of normal.
  • Criteria must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin (≥ approximately 3 months).
  • Creatinine clearance (CrCl) should be calculated per institutional standard. Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.

Who cannot join

  • 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:
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  • 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.
  • Note: A one-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) for non-CNS disease.
  • Has immunosuppression implying the continued use of systemic (at prednisone dose equivalent of >10 mg) or topical steroids, at or near, the planned intramuscular injection site or the use of immunosuppressive agents for any concurrent condition in the 4 weeks prior to first study treatment administration. Inhaled and eye drop containing corticosteroids are permitted.
  • Has received a live-virus vaccination within 30 days of pembrolizumab start. Seasonal flu vaccines that do not contain live virus are permitted. Covid-19 vaccines are permitted under the following guidance: mRNA Covid-19 vaccines are permitted if administered more than 2 weeks prior to Study Day 1, and Covid19 Adenovirus-based vaccines are accepted if administrated at least 6 months before Study Day 1.
  • Administration of killed vaccines are allowed.
  • Has an active severe infection requiring therapy.
  • Has active HBV or HCV infection that requires treatment, or at risk for HBV reactivation (i.e., positive hepatitis B surface antigen [HBsAg]). Patients with negative HBsAg and positive total hepatitis B core antibody may be included if HBV DNA is undetectable at the time of screening. Patients who are positive for HCV antibody are eligible only if the PCR test is negative for HCV RNA. Patients with known current or prior HBV infection must have HBsAg and HBV DNA testing during screening and those with current or previous HCV infection must have HCV DNA testing.
  • Has a chronic illness including, but not limited to, chronic heart failure, coronary heart disease, cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Has any history of anaphylaxis in reaction to a vaccination.
  • Is a woman who is pregnant or breastfeeding.
  • Any condition in the judgment of the Investigator, which makes the patient unsuitable for study participation; including psychological condition.
  • Has known hypersensitivity to pembrolizumab or to components of the Nous-209 study therapy or its analogues (including a known history of allergy to egg proteins).
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease
  • ≥5 years before the first dose of study treatment and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease.
  • Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to first dose of study treatment or concurrent enrolment in another clinical study.
  • Has active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
  • Is receiving growth factors including, but not limited to, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc., within 4 weeks of study drug administration.
  • Revaccination Eligibility Criteria for participants receiving Nous-209 with pembrolizumab (Phase II)
  • All participants that have been treated with Nous-209 and pembrolizumab combination in Phase IIa and in Phase IIb (Cohorts C and D) will be offered revaccination with Nous209 approximately 6 months after starting treatment (Table 3: Schedule of Activities for revaccination of eligible patients in Phase IIa and Phase IIb (Cohorts C and D)) providing the following criteria are met:
  • Being in objective radiological stable disease according to RECIST v1.1 without any prior evidence of Partial response (PR), complete response (CR), or progressive disease (PD), based on the last available on-treatment scan prior to revaccination.
  • Have no limiting toxicities preventing further administration of pembrolizumab (see Appendix 4: Management of Immune-Related Adverse Events).
  • Continues to fulfil the eligibility criteria for enrolment, except for the following inclusion criterion of Cohort C participants:
  • •9. Not have been previously treated with a (licensed or experimental) anti-PD1 or anti-PD-L1 checkpoint inhibitor.
  • Revaccination is not permitted for patients in Phase IIb Cohort C receiving pembrolizumab only.
  • Participants who meet the criteria for revaccination may only receive revaccination once.
  • During the revaccination period, participants will receive the same prime-boost vaccination doses and regimen of GAd20-209 FSP and MVA-209-FSP as in the original vaccination treatment period. Participants will continue to receive pembrolizumab at 200 mg Q3W.
  • Image acquisitions and tumour assessments should continue on their regular imaging schedule for the duration of treatment (see Section 7.1 Schedule of Activities (SoA) (Phase II)).

Trial locations and contacts

46 sites in 6 countries.

46 sites in 6 countries

Spain21 sites

  • Hospital Universitario de A Coruna

    A Coruña, 15006

  • Hospital Del Mar

    Barcelona, 08003

  • Hospital Universitari Dexeus

    Barcelona, 08028

  • Hospital Vall d'Hebron

    Barcelona, 08035

  • Institut Catala d'Oncologia Hospitalet

    Barcelona, 08908

  • Hospital Clinic de Barcelona

    Barcelona

  • Hospital Universitario Reina Sofia

    Córdoba, 14004

  • Hospital Universitario Virgen de las Nieves

    Granada, 18014

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28007

  • Clinica Universidad de Navarra

    Madrid, 28027

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario HM Sanchinarro

    Madrid

  • Clinica Universidad de Navarra

    Pamplona, 31008

  • Complejo Asistencial de Salamanca

    Salamanca, 37007

  • Hospital Universitario Marques de Valdecilla

    Santander

  • Hospital Clínico Universitario de Santiago de Compostela

    Santiago de Compostela, 15706

  • Hospital General Universitario de Valencia

    Valencia, 46014

  • University Clinical Hospital Valencia

    Valencia

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

United States13 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14203

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Goshen Center for Cancer Care

    Goshen, Indiana, 46526

  • MD Anderson Cancer Center (MDACC)

    Houston, Texas, 77030

  • City of Hope Comprehensive Cancer Center

    Irvine, California, 92618

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90089

  • Mt. Sinai

    Miami Beach, Florida, 33140

  • NYU Langone Medical Center

    New York, New York, 10016

  • Weill Cornell Medicine / New York-Presbyterian Hospital

    New York, New York, 10021

  • USC Norris Comprehensive Cancer Center

    Newport Beach, California, 92663

  • Boca Raton Clinical Research

    Plantation, Florida, 33322

  • Washington University School of Medicine, Division of Oncology

    St Louis, Missouri, 63110

Other trials in United States

Italy6 sites

  • Aorn Sg Moscati

    Avellino, 83100

  • Candiolo cancer Center,FPO IRCCS

    Candiolo, 10060

  • IRCCS Ospedale San Raffaele

    Milan, 20132

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

  • Ospedale Niguarda

    Milan, 20162

  • AOUS Policlinico Le Scotte

    Siena, 53100

Other trials in Italy

Belgium3 sites

  • Cliniques Universitaires Saint-Luc - Centre du Cancer

    Brussels, 1200

  • Centre Hospitalier de l'Ardenne - Libramont - Clinique du Sein

    Libramont, 6800

  • CHU de Liège

    Liège, 4000

Other trials in Belgium

Canada2 sites

  • Mount Sinai Hospital

    Toronto, M5G 2M9

  • Princess Margaret Cancer Center

    Toronto, M5G 2M9

Other trials in Canada

United Kingdom1 site

  • University College London Hospitals NHS Foundation Trust Cancer Clinical Trials Unit

    London

Other trials in United Kingdom

About this study

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

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.

Read the 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.

Being tested
GAd-209-FSP low dose, MVA-209-FSP low dose, GAd-209-FSP high dose, MVA-209-FSP high dose, GAd20-209-FSP, RP2D
Keywords
unresectable or metastatic dMMR tumor, MSI-H CRC, gastric tumor, gastro-esophageal junction (G-E junction) tumor
Medical subject headings
Stomach Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GAd-209-FSP low doseBiological

    GAd20-209-FSP IP, low dose

  • MVA-209-FSP low doseBiological

    MVA-209-FSP IP, low dose

  • GAd-209-FSP high doseBiological

    GAd20-209-FSP IP, high dose

  • MVA-209-FSP high doseBiological

    MVA-209-FSP IP, high dose

  • GAd20-209-FSP, RP2DBiological

    GAd20-209-FSP IP, RP2D

  • MVA-209-FSP, RP2DBiological

    MVA-209-FSP IP, RP2D

  • KEYTRUDA®Drug

    Also called pembrolizumab

    anti-PD-1 checkpoint inhibitor (200 mg; Q3W)

Study groups in NCT04041310
Study groupRoleWhat they receive
Cohort A - Dose-escalationExperimentalPhase 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.
Receives: Biological: GAd-209-FSP low dose; Biological: MVA-209-FSP low dose; Drug: KEYTRUDA®
Cohort B - Expansion Cohort Phase IExperimentalPhase 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.
Receives: Biological: GAd-209-FSP high dose; Biological: MVA-209-FSP high dose; Drug: KEYTRUDA®
Cohort C - Expansion cohort Phase IIExperimentalPhase 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.
Receives: Biological: GAd20-209-FSP, RP2D; Biological: MVA-209-FSP, RP2D; Drug: KEYTRUDA®
Cohort D - Expansion cohort Phase IIExperimentalPhase 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.
Receives: Biological: GAd20-209-FSP, RP2D; Biological: MVA-209-FSP, RP2D; Drug: KEYTRUDA®

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity (DLT assessment), in Phase I, Cohort A

    Toxicity analyzed within 28-days from the administration of the prime vaccination with GAd20-209-FSP

    Measured: Within 28 days

  2. 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.

    Measured: Up to 110 weeks

  3. Overall Response Rate (ORR) at any time during the study, in Phase II (Cohort C and D).

    Assessed using RECIST v1.1

    Measured: 18 months

Secondary outcomes (2)

  1. Immunogenicity (T cell responses against vaccine FSPs) in Phase I, Cohorts A and B

    PBMC-derived T cell responses against vaccine FSPs, as measured by IFN-gamma ELISpot

    Measured: Through study completion, an average of 2 years

  2. Safety and tolerability (local and systemic AEs), in Phase II (Cohort C and D)

    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.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2019
  2. Study start21 Oct 2019
  3. Primary completion30 Oct 2026 (estimated)
  4. Study completion30 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Phase I. Part 1. Main Study of 26 weeks. Cohort A - Dose escalation. Cohort B - Expansion Cohort at RP2D Phase I. Part 2. Extended Follow-up week 27 to 110 in Cohorts A and B. Phase II: Expansion at RP2D of Nous-209 vaccine plus pembrolizumab combination therapy in adult subjects. * Cohort C (Phase II) - 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 who have had radiographic progression (PD) after having a best response of stable disease (SD) or better on/after anti-PD1 treatment. * In Phase I: 21 to 34 subjects will be enrolled across Cohorts A and B. * In Phase II: Cohort C: up to approximately 63 subjects, Cohort D: up to approximately 18 subjects
Masking
None (open label)
Enrolment
115 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04041310
Sponsor's protocol ID
NOUS-209-01
Other IDs
IND #018954, 2021-002823-40, MK-3475-E58, KEYNOTE-E58
Status last verified
Feb 2026
First submitted
21 Jul 2019
Last updated
13 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Crespo-Cruz M, Rodriguez-Justo M, Humphries A, Plumb A, Antoniou A, Monahan K, Runswick S, Capone A, Antonucci L, Garzia I, Micarelli E, Scarselli E, D'Alise AM, Gogov S, Shiu KK. Colonic Polyp Regression After Nous-209 Cancer Immunotherapy: A Clinical Trial Case Report. J Immunother Precis Oncol. 2026 Aug 24;9(4):124-129. doi: 10.36401/JIPO-25-32. eCollection 2026 Nov.

    PubMed 42662364

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GAd-209-FSP low dose, MVA-209-FSP low dose and GAd-209-FSP high dose in people with Solid Tumor, Adult, run by Nouscom SRL at 46 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 51 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in Spain, United States, Italy, Belgium, Canada and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity (DLT assessment), in Phase I, Cohort A (time frame: Within 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04041310, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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