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Nous-PEV: a Novel Immunotherapy for Lung Cancer and Melanoma

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ClinicalTrials.gov Identifier: NCT04990479
Recruitment Status : Recruiting
First Posted : August 4, 2021
Last Update Posted : September 8, 2021
Sponsor:
Information provided by (Responsible Party):
Nouscom SRL

Brief Summary:
This is an international, multicenter, open-label, multiple cohort, First in Human, phase 1b clinical study, designed to evaluate safety, tolerability, and immunogenicity, and to detect any preliminary evidence of anti-tumor activity of a personalized vaccine (PEV) based on GAd-PEV priming and MVA-PEV boosting, combined with SoC first-line immunotherapy using an anti-PD-1 checkpoint inhibitor in patients with unresectable stage III/IV cutaneous melanoma or with stage IV NSCLC (PDL1 ≥ 50%). The PEV vaccines will be prepared on an individual basis, following a tumor biopsy performed at the time of screening and subsequent NGS analysis, to identify patient-specific tumor mutations. Both neoantigen-encoding genetic vaccines are administered intramuscularly using 1 prime with GAd-PEV and 3 boosts with MVA-PEV in combination with the licensed programmed death receptor-1 (PD-1)-blocking antibody pembrolizumab in adult patients in patients with unresectable stage III/IV cutaneous melanoma (Cohort a) or with stage IV NSCLC (PDL1 ≥ 50%) (Cohort b).

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Non-Small-Cell Lung Carcinoma Biological: GAd-PEV Biological: MVA-PEV Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Treatment Cohorts of the study.

Part 1:

• Cohort 1a: 3 patients (expandable to 9) with unresectable stage III / IV Cutaneous Melanoma.

Part 2

  • Cohort 2a: 13 patients with unresectable stage III / IV Cutaneous Melanoma.
  • Cohort 2b:12 patients with stage IV NSCLC (PDL1≥ 50%). In all cohorts, the treatment consists of four Nous-PEV vaccine administrations in combination with pembrolizumab as SoC.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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%)
Actual Study Start Date : April 7, 2021
Estimated Primary Completion Date : October 31, 2024
Estimated Study Completion Date : October 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Cohort 1a
Cohort 1a: 3 patients (expandable to 9) with unresectable stage III / IV Cutaneous Melanoma.
Biological: GAd-PEV
Priming phase including 1 GAd-PEV administration with Standard of Care pembrolizumab (cycle 4).

Biological: MVA-PEV
Boosting phase including 3 boosting administrations of MVA-PEV with Standard of Care pembrolizumab (cycles 5, 6 and 7).

Experimental: Cohort 2a
Cohort 2a:13 patients with unresectable stage III / IV Cutaneous Melanoma.
Biological: GAd-PEV
Priming phase including 1 GAd-PEV administration with Standard of Care pembrolizumab (cycle 4).

Biological: MVA-PEV
Boosting phase including 3 boosting administrations of MVA-PEV with Standard of Care pembrolizumab (cycles 5, 6 and 7).

Experimental: Cohort 2b
Cohort 2b: 12 patients with stage IV NSCLC (PDL1≥ 50%).
Biological: GAd-PEV
Priming phase including 1 GAd-PEV administration with Standard of Care pembrolizumab (cycle 4).

Biological: MVA-PEV
Boosting phase including 3 boosting administrations of MVA-PEV with Standard of Care pembrolizumab (cycles 5, 6 and 7).




Primary Outcome Measures :
  1. 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 ]
    • Frequency, duration, and severity of adverse events (AEs) and serious adverse events (SAEs) using CTCAE v5.0 criteria.
    • Changes in vital signs and clinical evaluations.
    • Changes in clinical laboratory blood samples.
    • Dose-limiting toxicity (DLT)


Secondary Outcome Measures :
  1. RP2D confirmation 2. Clinical efficacy: [ Time Frame: Up to 110 weeks ]
    RP2D confirmation based on safety and tolerability

  2. Clinical efficacy [ Time Frame: Up to 110 weeks ]
    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


Other Outcome Measures:
  1. Exploratory outcome: immunogenicity [ Time Frame: Up to 110 weeks ]
    PBMC-derived T-cell responses against vaccine FSPs, as measured by IFN-gamma ELISpot



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Main Inclusion Criteria for Patients in Cohorts 1a and 2a:

  1. Age ≥ 18 years.
  2. Patients with histologically or cytologically confirmed unresectable stage III or stage IV Cutaneous Melanoma, as per American Joint Committee on Cancer (AJCC) staging system (8th edition).
  3. 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.
  4. 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
  5. Presence of at least one lesion amenable to repeated biopsy, ideally not the one being used for measuring.
  6. Willingness to undergo a minimum of two fresh lesion biopsies (pre-treatment and on-treatment).
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
  8. Life expectancy of at least 12 months.
  9. Adequate renal, hepatic, and hematologic functions.
  10. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and woman of childbearing potential willing to use adequate contraception.
  11. A male patient must agree to use adequate contraception.

Main Inclusion Criteria for Patients in Cohort 2b:

  1. Age ≥ 18 years.
  2. Histologically or cytologically confirmed stage IV squamous or non-squamous NSCLC without EGFR or ALK /ROS1/RET genomic alteration.
  3. Tumor expression with PD-L1 ≥50% tumor proportion score (TPS).
  4. First-line treatment-naïve patients.
  5. 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.
  6. 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.
  7. Presence of at least one tumor lesion amenable to repeated biopsy, if possible, ideally not the one being used for measuring.
  8. Willingness to undergo a minimum of two fresh tumor biopsies (pre-treatment and on-treatment).
  9. ECOG performance status 0 to 1.
  10. Life expectancy of at least 6 months.
  11. Adequate renal, hepatic, and hematologic functions.
  12. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and woman of childbearing potential willing to use adequate contraception.
  13. A male patient must agree to use adequate contraception.

Main Exclusion Criteria for patients in all Cohorts:

  1. Currently receiving treatment with another investigational medicinal product.
  2. Prior therapy with immune checkpoint inhibitors. Patients must not have received any investigational immunotherapy either.
  3. 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.
  4. Prior allogenic tissue or solid organ transplant.
  5. Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids and/or whose pulse oxymetry is less than 92% "on room air".
  6. Major surgery within 12 weeks before enrolment.
  7. Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry.
  8. 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.
  9. Previous vaccination (either therapeutic and/or prophylactic) against cancer.
  10. History of autoimmune disease in the last 5 years, including any active autoimmune disease except vitiligo or childhood asthma.
  11. Chronic or concurrent active infectious disease requiring systemic antibodies, antifungal, or antiviral treatment.
  12. 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.
  13. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or at risk for HBV reactivation.
  14. Known CNS metastasis and/or carcinomatous meningitis.
  15. Known cerebral edema.
  16. Live vaccine received within 30 days before treatment initiation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04990479


Contacts
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Contact: Patricia Delaite, MD (+39) 06 96036299 p.delaite@nouscom.com
Contact: Elisa Scarselli, MD (+39) 06 96036299 e.scarselli@nouscom.com

Locations
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Belgium
Grand Hopital de Charleroi, Grand Rue 3, 6000 Charleroi (NOUS-PEV-01 site BE2) Active, not recruiting
Charleroi, Belgium, 6000
UZ Leuven Hospital, Campus Gasthuisberg, Herestraat 49, 3000 Leuven (NOUS-PEV-01 site BE1) Recruiting
Leuven, Belgium, 3000
Contact: Oliver Bechter, MD       Oliver.bechter@uzleuven.be   
Contact: Ingeborg Wauters       ingeborg.wauters@uzleuven.be   
Spain
Institut Catalá d'Oncologia ICO L'Hospitalet. Av Gran Via de L'Hospitalet 199-203. 08908 L'Hospitalet de Llobregat, Barcelona, Spain (NOUS-PEV-01 site ES4) Not yet recruiting
Barcelona, Spain, 08908
Contact: Juan Martin-Liberal, MD       jmartinliberal@iconcologia.net   
Contact: Maria del Carmen Garcia Rodriguez       mcgarciarodriguez@iconcologia.net   
START Madrid - Centro Integral Oncológico Clara Campal, HM CIOCC Hospital Universitario HM Sanchinarro, 28050 Madrid. Spain (NOUS-PEV-01 site ES1) Active, not recruiting
Madrid, Spain, 28050
START Madrid-FJD, Hospital Fundación Jiménez Diaz Avda. Reyes Católicos 2. 28040, Madrid, Spain (NOUS-PEV-01 site ES2) Active, not recruiting
Madrid, Spain
Instituto de Investigación Sanitaria INCLIVA - Hospital Clínico Universitario de Valencia. Av. Blasco Ibáñez, 17 CP 46010 Valencia, Spain (NOUS-PEV-01 site ES3) Not yet recruiting
Valencia, Spain, 46010
Contact: Andrés Cervantes Ruipérez, MD       andres.cervantes@uv.es   
Contact: Inma Blasco       iblasco@incliva.es   
United Kingdom
Cancer Research UK Edinburgh Centre. Western General Hospital, Edinburgh, EH4 2SP, UK (NOUS-PEV-01 site UK1) Active, not recruiting
Edinburgh, Scotland, United Kingdom, EH4 2SP
Sponsors and Collaborators
Nouscom SRL
Investigators
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Principal Investigator: Stefan Symeonides University of Edinburgh
Additional Information:
Publications:
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Responsible Party: Nouscom SRL
ClinicalTrials.gov Identifier: NCT04990479    
Other Study ID Numbers: NOUS-PEV-01
2019-004759-35 ( EudraCT Number )
First Posted: August 4, 2021    Key Record Dates
Last Update Posted: September 8, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Melanoma
Carcinoma, Non-Small-Cell Lung
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms