- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04990479
Nous-PEV: a Novel Immunotherapy for Lung Cancer and Melanoma
An Open-Label, Multicenter, Non-Randomized, Dose-Confirmation and Cohort-Expansion Phase 1b Study to Evaluate the Safety, Tolerability, and Anti-Tumor Activity of Nous-PEV, With Pembrolizumab, in Patients With Unresectable Stage III / IV Cutaneous Melanoma and With Stage IV NSCLC (PDL1≥ 50%)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Overall Study Design:
• This is an open-label, non-randomized, dose-confirmation and cohort expansion phase 1b first-in-human study, in which 28 patients, expandable up to 34 evaluable patients in case of DLT.
Study IMPs:
Nous-PEV vaccine is composed of 2 sets of IMPs:
- GAd-PEV
- MVA-PEV
Treatment phases:
A) Induction phase with pembrolizumab (cycles 1, 2 and 3). B) Priming phase including 1 GAd-PEV administration with pembrolizumab (cycle 4).
C) Boosting phase including 3 boosting administrations of MVA-PEV with pembrolizumab (cycles 5, 6 and 7).
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Patricia Delaite, MD
- Phone Number: (+39) 06 96036299
- Email: p.delaite@nouscom.com
Study Contact Backup
- Name: Elisa Scarselli, MD
- Phone Number: (+39) 06 96036299
- Email: e.scarselli@nouscom.com
Study Locations
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Charleroi, Belgium, 6000
- Grand Hopital de Charleroi, Grand Rue 3, 6000 Charleroi
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Leuven, Belgium, 3000
- UZ Leuven Hospital, Campus Gasthuisberg, Herestraat 49, 3000 Leuven
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Barcelona, Spain, 08908
- Institut Catalá d'Oncologia ICO L'Hospitalet. Av Gran Via de L'Hospitalet 199-203. 08908 L'Hospitalet de Llobregat, Barcelona, Spain
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Madrid, Spain, 28050
- START Madrid - Centro Integral Oncológico Clara Campal, HM CIOCC Hospital Universitario HM Sanchinarro, 28050 Madrid. Spain
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Madrid, Spain
- START Madrid-FJD, Hospital Fundación Jiménez Diaz Avda. Reyes Católicos 2. 28040, Madrid, Spain
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Valencia, Spain, 46010
- Instituto de Investigación Sanitaria INCLIVA - Hospital Clínico Universitario de Valencia. Av. Blasco Ibáñez, 17 CP 46010 Valencia, Spain
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Scotland
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Edinburgh, Scotland, United Kingdom, EH4 2SP
- Cancer Research UK Edinburgh Centre. Western General Hospital, Edinburgh, EH4 2SP, UK
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Main Inclusion Criteria for Patients in Cohorts 1a and 2a:
- Age ≥ 18 years.
- Patients with histologically or cytologically confirmed unresectable stage III or stage IV Cutaneous Melanoma, as per AJCC staging system (8th edition). First-line treatment-naive patients.
- Participation in this trial will be dependent upon supplying tumor tissue from newly obtained specimen. Newly obtained biopsies of a tumor lesion, not previously irradiated, must be provided in the form of excisional biopsies, resected tissue or core needle biopsies.
- Presence of at least 1 measurable lesion by computed tomography or magnetic resonance imaging per RECIST v1.1 by the local site Investigator / radiologist assessment
- Presence of at least one lesion amenable to repeated biopsy, ideally not the one being used for measuring.
- Willingness to undergo a minimum of two fresh lesion biopsies (pre-treatment and on-treatment).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
- Life expectancy of at least 12 months.
- Adequate renal, hepatic, and hematologic functions
- A female patient is eligible to participate if she is not pregnant and not breastfeeding
- A male patient must agree to use an adequate contraception
Main Inclusion Criteria for Patients in Cohort 2b:
- Age ≥ 18 years.
- Histologically or cytologically confirmed stage IV squamous or non-squamous NSCLC without EGFR or ALK/ROS1 /RET genomic alteration.
- Tumor expression with PD-L1 ≥50% tumor proportion score (TPS).
- First-line treatment-naïve patients.
- Participation in this trial will be dependent upon supplying tumor tissue from a newly obtained specimen. Newly obtained biopsies of a tumor lesion, not previously irradiated, must be provided in the form of excisional biopsies, resected tissue or core needle biopsies.
- Presence of at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 as determined by the local site Investigator / radiologist assessment.
- Presence of at least one tumor lesion amenable to repeated biopsy, if possible, ideally not the one being used for measuring.
- Willingness to undergo a minimum of two fresh tumor biopsies (pre-treatment and on-treatment).
- ECOG performance status 0 to 1.
- Life expectancy of at least 6 months.
- Adequate renal, hepatic, and hematologic functions
- A female patient is eligible to participate if she is not pregnant and not breastfeeding
- A male patient must agree to use a contraceptive 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.
Main Exclusion Criteria for patients in all Cohorts:
- Currently receiving treatment with another investigational medicinal product.
- Prior therapy with immune checkpoint inhibitors. Patients must not have received any investigational immunotherapy either.
- Prior radiotherapy within 2 weeks of enrolment, or within 4 weeks of enrolment in the case of radiation to central nervous system (CNS), which requires ≥ 4-week washout.
- Prior allogenic tissue or solid organ transplant.
- Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids and/or whose pulse oximetry is less than 92% "on room air".
- Limiting cardiac criteria: prolonged QT interval or QT prolongation risk factors, clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g. complete LBBB, third degree heart block, risk of arrythmic events, ejection fraction under lower limit of normal.
- Major (according to the Investigator's judgment) surgery within 12 weeks before enrolment.
- Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry.
- Immunosuppression including the continued use of systemic (at prednisone dose equivalent of > 10 mg) or topical steroids at or near the planned i.m. 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.
- Previous vaccination (either therapeutic and/or prophylactic) against cancer.
- History of autoimmune disease in the last 5 years, including any active autoimmune disease except vitiligo or childhood asthma.
- Chronic or concurrent active infectious disease requiring systemic antibodies, antifungal, or antiviral treatment.
- Known Medical History of human immunodeficiency virus (HIV) infection or known Medical History of acquired immunodeficiency syndrome (AIDS). HIV testing is not required unless mandated by the local health authority.
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or at risk for HBV reactivation
- Known CNS metastasis and/or carcinomatous meningitis.
- Known cerebral edema.
- Live vaccine received within 30 days before treatment initiation.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cohort 1a
Cohort 1a: 3 patients (expandable to 9) with unresectable stage III / IV Cutaneous Melanoma.
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Priming phase including 1 GAd-PEV administration with Standard of Care pembrolizumab (cycle 4).
Boosting phase including 3 boosting administrations of MVA-PEV with Standard of Care pembrolizumab (cycles 5, 6 and 7).
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Experimental: Cohort 2a
Cohort 2a:13 patients with unresectable stage III / IV Cutaneous Melanoma.
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Priming phase including 1 GAd-PEV administration with Standard of Care pembrolizumab (cycle 4).
Boosting phase including 3 boosting administrations of MVA-PEV with Standard of Care pembrolizumab (cycles 5, 6 and 7).
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Experimental: Cohort 2b
Cohort 2b: 12 patients with stage IV NSCLC (PDL1≥ 50%).
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Priming phase including 1 GAd-PEV administration with Standard of Care pembrolizumab (cycle 4).
Boosting phase including 3 boosting administrations of MVA-PEV with Standard of Care pembrolizumab (cycles 5, 6 and 7).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Safety and tolerability: incidence of treatment- emerging adverse events. AEs characterized by type, severity (graded by CTCAE v.5.0), Timing, seriousness and relationship to study treatments.
Time Frame: Up to 110 weeks
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Up to 110 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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RP2D confirmation 2. Clinical efficacy:
Time Frame: Up to 110 weeks
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RP2D confirmation based on safety and tolerability
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Up to 110 weeks
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Clinical efficacy
Time Frame: Up to 110 weeks
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Clinical efficacy based on Overall response rate (ORR); Best overall response (BOR); Duration of response (DoR); Progression-free survival (PFS); Overall survival (OS), all as defined in tumor imaging, RECIST 1.1
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Up to 110 weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Exploratory outcome: immunogenicity
Time Frame: Up to 110 weeks
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PBMC-derived T-cell responses against vaccine FSPs, as measured by IFN-gamma ELISpot
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Up to 110 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Sven Gogov, MD, Nouscom SRL
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Lung Neoplasms
- Neuroendocrine Tumors
- Nevi and Melanomas
- Carcinoma, Non-Small-Cell Lung
- Melanoma
Other Study ID Numbers
- NOUS-PEV-01
- 2019-004759-35 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Melanoma (Skin)
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Rutgers, The State University of New JerseyNational Cancer Institute (NCI); University of VirginiaCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage III Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin Melanoma | Stage 0 Skin Melanoma | Stage I Skin Melanoma | Stage II Skin MelanomaUnited States
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William CarsonSchering-PloughCompletedStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin MelanomaUnited States
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Roswell Park Cancer InstituteNational Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin MelanomaUnited States
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National Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin MelanomaUnited States
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Roswell Park Cancer InstituteCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IB Skin MelanomaUnited States
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Mayo ClinicNational Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin MelanomaUnited States
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Emory UniversityGenentech, Inc.Active, not recruitingStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Unresectable Melanoma | Stage III Melanoma | Stage IIIA Skin Melanoma | Cutaneous Melanoma, Stage III | Cutaneous Melanoma, Stage IVUnited States
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National Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Mucosal Melanoma | Stage IIIA Skin MelanomaUnited States, Australia
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Incyte Corporation; University of VirginiaCompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Mucosal Melanoma | Stage IV Uveal Melanoma | Stage IIIA Skin Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal Melanoma | Recurrent Uveal MelanomaUnited States
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National Cancer Institute (NCI)CompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage IIIA Skin MelanomaUnited States
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Neurologix, Inc.Terminated
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MeiraGTx, LLCActive, not recruitingParkinson DiseaseUnited States
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Zagazig UniversityUnknownHypertension With PregnancyEgypt
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Hospices Civils de LyonRecruitingGAD-receptor Antibodies-associated EncephalitisFrance
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NYU Langone HealthCompleted
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University of Texas at AustinWithdrawn
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Lund UniversityRegion SkaneTerminatedDiabetes Mellitus, Type 1 | Prediabetic StateSweden