## Protocol Section
### Identification Module
**NCT ID:** NCT04990479

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

**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%)

#### Organization Study ID Info
**ID:** NOUS-PEV-01
#### Organization
**Class:** INDUSTRY
**Full Name:** Nouscom SRL
#### Secondary ID Infos
**ID:** 2019-004759-35
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2024-10-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-03-13

**Type:** ACTUAL

**Last Update Submit Date:** 2023-03-09

**Overall Status:** ACTIVE_NOT_RECRUITING

#### Primary Completion Date
**Date:** 2024-10-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2021-06-11

**Type:** ACTUAL

**Status Verified Date:** 2023-03

#### Study First Post Date
**Date:** 2021-08-04
**Type:** ACTUAL
**Study First Submit Date:** 2021-07-15
**Study First Submit QC Date:** 2021-07-26
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Nouscom SRL

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**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).

**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).

### Conditions Module

**Conditions:**

- Melanoma (Skin)

- Non-Small-Cell Lung Carcinoma

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** SEQUENTIAL

**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 Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 34

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Biological: GAd-PEV

- Biological: MVA-PEV

**Label:** Cohort 1a

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Biological: GAd-PEV

- Biological: MVA-PEV

**Label:** Cohort 2a

**Type:** EXPERIMENTAL

#### Arm Group 3

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

**Intervention Names:**

- Biological: GAd-PEV

- Biological: MVA-PEV

**Label:** Cohort 2b

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cohort 1a

- Cohort 2a

- Cohort 2b

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

**Name:** GAd-PEV

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

- Cohort 1a

- Cohort 2a

- Cohort 2b

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

**Name:** MVA-PEV

**Type:** BIOLOGICAL

### Outcomes Module

#### Other Outcomes

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

**Measure:** Exploratory outcome: immunogenicity

**Time Frame:** Up to 110 weeks

#### Primary Outcomes

**Description:** * 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)

**Measure:** 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

#### Secondary Outcomes

**Description:** RP2D confirmation based on safety and tolerability

**Measure:** RP2D confirmation 2. Clinical efficacy:

**Time Frame:** Up to 110 weeks

**Description:** 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

**Measure:** Clinical efficacy

**Time Frame:** Up to 110 weeks

### Eligibility Module

**Eligibility 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 AJCC staging system (8th edition). First-line treatment-naive patients.
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 and not breastfeeding
11. A male patient must agree to use an 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 and not breastfeeding
13. 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:

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 oximetry is less than 92% "on room air".
6. 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.
7. Major (according to the Investigator's judgment) surgery within 12 weeks before enrolment.
8. Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry.
9. 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.
10. Previous vaccination (either therapeutic and/or prophylactic) against cancer.
11. History of autoimmune disease in the last 5 years, including any active autoimmune disease except vitiligo or childhood asthma.
12. Chronic or concurrent active infectious disease requiring systemic antibodies, antifungal, or antiviral treatment.
13. 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.
14. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, or at risk for HBV reactivation
15. Known CNS metastasis and/or carcinomatous meningitis.
16. Known cerebral edema.
17. Live vaccine received within 30 days before treatment initiation.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Charleroi

**Country:** Belgium

**Facility:** Grand Hopital de Charleroi, Grand Rue 3, 6000 Charleroi

**Zip:** 6000

**Location 2:**

**City:** Leuven

**Country:** Belgium

**Facility:** UZ Leuven Hospital, Campus Gasthuisberg, Herestraat 49, 3000 Leuven

**Zip:** 3000

**Location 3:**

**City:** Barcelona

**Country:** Spain

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

**Zip:** 08908

**Location 4:**

**City:** Madrid

**Country:** Spain

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

**Zip:** 28050

**Location 5:**

**City:** Madrid

**Country:** Spain

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

**Location 6:**

**City:** Valencia

**Country:** Spain

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

**Zip:** 46010

**Location 7:**

**City:** Edinburgh

**Country:** United Kingdom

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

**State:** Scotland

**Zip:** EH4 2SP

#### Overall Officials

**Official 1:**

**Affiliation:** Nouscom SRL

**Name:** Sven Gogov, MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** 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

#### See Also Links

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

**URL:** https://pubmed.ncbi.nlm.nih.gov/34452005/

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018358

- Term: Neuroendocrine Tumors

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

- ID: D000018326

- Term: Nevi and Melanomas

- ID: D000012878

- Term: Skin Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000012871

- Term: Skin Diseases

- ID: D000008175

- Term: Lung Neoplasms

- ID: D000012142

- Term: Respiratory Tract Neoplasms

- ID: D000013899

- Term: Thoracic Neoplasms

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000002283

- Term: Carcinoma, Bronchogenic

- ID: D000001984

- Term: Bronchial Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M11172

- Name: Lung Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M5546

- Name: Carcinoma, Non-Small-Cell Lung

- Relevance: HIGH

- As Found: Non-Small Cell Lung Carcinoma

- ID: M11528

- Name: Melanoma

- Relevance: HIGH

- As Found: Melanoma

- ID: M3212

- Name: Melanoma, Cutaneous Malignant

- Relevance: LOW

- As Found: Unknown

- ID: M20495

- Name: Neuroendocrine Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M12448

- Name: Nevus, Pigmented

- Relevance: LOW

- As Found: Unknown

- ID: M12446

- Name: Nevus

- Relevance: LOW

- As Found: Unknown

- ID: M20470

- Name: Nevi and Melanomas

- Relevance: LOW

- As Found: Unknown

- ID: M15681

- Name: Skin Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14979

- Name: Respiratory Tract Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16658

- Name: Thoracic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5540

- Name: Carcinoma, Bronchogenic

- Relevance: LOW

- As Found: Unknown

- ID: M5260

- Name: Bronchial Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: T4091

- Name: Neuroendocrine Tumor

- Relevance: LOW

- As Found: Unknown

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008545

- Term: Melanoma

- ID: D000002289

- Term: Carcinoma, Non-Small-Cell Lung

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M349416

- Name: Pembrolizumab

- Relevance: LOW

- As Found: Unknown

- ID: M2853

- Name: Immunomodulating Agents

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
