Trial Title:
Nous-PEV: a Novel Immunotherapy for Lung Cancer and Melanoma
NCT ID:
NCT04990479
Condition:
Melanoma (Skin)
Non-Small-Cell Lung Carcinoma
Conditions: Official terms:
Melanoma
Carcinoma, Non-Small-Cell Lung
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
GAd-PEV
Description:
Priming phase including 1 GAd-PEV administration with Standard of Care pembrolizumab
(cycle 4).
Arm group label:
Cohort 1a
Arm group label:
Cohort 2a
Arm group label:
Cohort 2b
Intervention type:
Biological
Intervention name:
MVA-PEV
Description:
Boosting phase including 3 boosting administrations of MVA-PEV with Standard of Care
pembrolizumab (cycles 5, 6 and 7).
Arm group label:
Cohort 1a
Arm group label:
Cohort 2a
Arm group label:
Cohort 2b
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).
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Grand Hopital de Charleroi, Grand Rue 3, 6000 Charleroi
Address:
City:
Charleroi
Zip:
6000
Country:
Belgium
Facility:
Name:
UZ Leuven Hospital, Campus Gasthuisberg, Herestraat 49, 3000 Leuven
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Facility:
Name:
Institut Catalá d'Oncologia ICO L'Hospitalet. Av Gran Via de L'Hospitalet 199-203. 08908 L'Hospitalet de Llobregat, Barcelona, Spain
Address:
City:
Barcelona
Zip:
08908
Country:
Spain
Facility:
Name:
START Madrid - Centro Integral Oncológico Clara Campal, HM CIOCC Hospital Universitario HM Sanchinarro, 28050 Madrid. Spain
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Facility:
Name:
START Madrid-FJD, Hospital Fundación Jiménez Diaz Avda. Reyes Católicos 2. 28040, Madrid, Spain
Address:
City:
Madrid
Country:
Spain
Facility:
Name:
Instituto de Investigación Sanitaria INCLIVA - Hospital Clínico Universitario de Valencia. Av. Blasco Ibáñez, 17 CP 46010 Valencia, Spain
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Facility:
Name:
Cancer Research UK Edinburgh Centre. Western General Hospital, Edinburgh, EH4 2SP, UK
Address:
City:
Edinburgh
Zip:
EH4 2SP
Country:
United Kingdom
Start date:
June 11, 2021
Completion date:
October 31, 2024
Lead sponsor:
Agency:
Nouscom SRL
Agency class:
Industry
Source:
Nouscom SRL
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT04990479
https://pubmed.ncbi.nlm.nih.gov/34452005/
