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

NCT04990479 | Terminated Phase 1 DMC

• 2 other identifiers: NOUS-PEV-012019-004759-35
• Study Type: interventional
• Target: 7
• Locations: 3 countries
• Sites: 7

Brief Summary

From Protocol v3.0 dated 16Jun2022. 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).

Conditions

Melanoma (Skin); Non-Small-Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (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.

  * 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)

  Up to 110 weeks

Secondary Outcomes (2)

• RP2D confirmation 2. Clinical efficacy:

  Up to 110 weeks

• Clinical efficacy

  Up to 110 weeks

Other Outcomes (1)

• Exploratory outcome: immunogenicity

  Up to 110 weeks

Study Arms (3)

Cohort 1a

EXPERIMENTAL

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

Biological: GAd-PEV; Biological: MVA-PEV

Cohort 2a

EXPERIMENTAL

Cohort 2a:13 patients with unresectable stage III / IV Cutaneous Melanoma.

Biological: GAd-PEV; Biological: MVA-PEV

Cohort 2b

EXPERIMENTAL

Cohort 2b: 12 patients with stage IV NSCLC (PDL1≥ 50%).

Biological: GAd-PEV; Biological: MVA-PEV

Interventions

GAd-PEV BIOLOGICAL

Priming phase including 1 GAd-PEV administration with Standard of Care pembrolizumab (cycle 4).

Cohort 1a; Cohort 2a; Cohort 2b

MVA-PEV BIOLOGICAL

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

Cohort 1a; Cohort 2a; Cohort 2b

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nouscom SRL: lead

Study Sites (7)

Grand Hopital de Charleroi, Grand Rue 3, 6000 Charleroi

Charleroi, 6000, Belgium

Location

UZ Leuven Hospital, Campus Gasthuisberg, Herestraat 49, 3000 Leuven

Leuven, 3000, Belgium

Location

Institut Catalá d'Oncologia ICO L'Hospitalet. Av Gran Via de L'Hospitalet 199-203. 08908 L'Hospitalet de Llobregat, Barcelona, Spain

Barcelona, 08908, Spain

Location

START Madrid - Centro Integral Oncológico Clara Campal, HM CIOCC Hospital Universitario HM Sanchinarro, 28050 Madrid. Spain

Madrid, 28050, Spain

Location

START Madrid-FJD, Hospital Fundación Jiménez Diaz Avda. Reyes Católicos 2. 28040, Madrid, Spain

Madrid, Spain

Location

Instituto de Investigación Sanitaria INCLIVA - Hospital Clínico Universitario de Valencia. Av. Blasco Ibáñez, 17 CP 46010 Valencia, Spain

Valencia, 46010, Spain

Location

Cancer Research UK Edinburgh Centre. Western General Hospital, Edinburgh, EH4 2SP, UK

Edinburgh, Scotland, EH4 2SP, United Kingdom

Location

Related Publications (2)

• Leoni G, D'Alise AM, Tucci FG, Micarelli E, Garzia I, De Lucia M, Langone F, Nocchi L, Cotugno G, Bartolomeo R, Romano G, Allocca S, Troise F, Nicosia A, Lahm A, Scarselli E. VENUS, a Novel Selection Approach to Improve the Accuracy of Neoantigens' Prediction. Vaccines (Basel). 2021 Aug 9;9(8):880. doi: 10.3390/vaccines9080880.

  PMID: 34452005 BACKGROUND

• D'Alise AM, Leoni G, Cotugno G, Siani L, Vitale R, Ruzza V, Garzia I, Antonucci L, Micarelli E, Venafra V, Gogov S, Capone A, Runswick S, Martin-Liberal J, Calvo E, Moreno V, Symeonides SN, Scarselli E, Bechter O. Phase I Trial of Viral Vector-Based Personalized Vaccination Elicits Robust Neoantigen-Specific Antitumor T-Cell Responses. Clin Cancer Res. 2024 Jun 3;30(11):2412-2423. doi: 10.1158/1078-0432.CCR-23-3940.

  PMID: 38506710 DERIVED

Related Links

• VENUS is a proprietary algorithm designed to enhance the predictive accuracy of personalized neoantigen selection, used in the NOUS-PEV-01 trial.

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Sven Gogov, MD

  Nouscom SRL

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: August 4, 2021
• Study Start: June 11, 2021
• Primary Completion: March 5, 2024
• Study Completion: March 5, 2024
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); GB (1); BE (2)