Nous-PEV (IMP) in combination with Pembrolizumab
Research type
Research Study
Full 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%)
IRAS ID
287199
Contact name
Stefan Symeonides
Contact email
Sponsor organisation
NOUSCOM SRL
Eudract number
2019-004759-35
Duration of Study in the UK
2 years, 7 months, 20 days
Research summary
Research Summary:
This is a First in Human clinical study in metastatic Stage IV Non-Small Cell Lung Cancer (NSCLC) and unresectable or metastatic Stage III/Stage IV Melanoma. The study will evaluate the safety, tolerability and immunogenicity of a personalised vaccine (PEV), combined with the standard of care treatment, Pembrolizumab.
Eligible participants must be 18 years and older. Participants will be seen at the approved research centres (Hospitals) in the UK, Belgium and Spain.
At least 28 participants, but up to 34, may be enrolled in this study.The Main Study will last 31 weeks from starting on Pembrolizumab. Participants will be enrolled in different cohorts depending on their disease indication. In all cohorts participants will undergo an Induction Phase (when they start the first-line treatment, Pembrolizumab, for 3 cycles of 21 days each), a Priming Phase (when the first personalised vaccine is administered in cycle 4), and a Boosting Phase (administration of the second personalised vaccine in cycles 5, 6 and 7).
Participants may attend more than 40 clinic visits over 2 years (standard of care would have been 17 to 35 visits). Study visits may last from 2 to 4 hours. Blood sampling and ECG tests will occur at most visits, CT scans will be performed regularly (every 9 weeks, so similar to to standard of care of every 9 to 12 weeks), rarely PET-CT scans instead of regular CT scans. There are two mandatory biopsies and a third optional biopsy.
After the first participant is treated, all safety data will be reviewed before the next two participants are included. This safety assessment will be repeated once those two participants are treated. Only then will further participants be included.
The Follow Up Period (from week 32 to week 110) will assess the long-term clinical benefit of the treatment.
Summary of Results:
Lay person Summary of Study NOUS-PEV-01
1. Study Name
This summary reports the results from only one study. Researchers must look at the results of many types of studies to understand which drugs work and how they work. It takes lots of people in many studies all around the world to advance medical science. Other studies may find different results.
1.1. Study name
Lay title: NOUS_PEV – A novel therapy for the treatment of lung cancer and melanoma Full 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 (PD-L1 ≥50%)
1.2 Protocol number: NOUS-PEV-01
1.3 EudraCT Number: 2019 -004759-35
1.4 Other Identifiers
US NCT number: NCT-004990479
2. Who Sponsored this study
Nouscom Srl, Via del Castel Romano 100, I-00128 Rome, Italy.
Further contact: Info@nouscom.com
3. General information about the clinical trial
3.1 When was this study done?
The study started on 11 June 2021 and ended on 05 March 2024.
The Sponsor decided to stop the study after 7 patients with skin cancer were treated, as the product was shown to be safe and didn’t cause any unwanted effects in the patients.
3. 2 Why was this study done?
This was an open label Phase I study. This means that both patients and the Investigator knew what they were getting and that the products had not been administered to anyone before this study.
Researchers wanted to know if the product of investigation, called Nous-PEV, in combination with pembrolizumab, is safe to treat patients with advanced (metastatic) cutaneous melanoma (skin cancer). Pembrolizumab is a type of medicine called immune-modulatory that doctors used to treat cancer. It can help your immune system to fight the cancer cells. When cells in the body divide without control they can form masses called “tumours”. Melanoma is a type of skin cancer that begins in the cells that produce pigment (called melanocytes) in your skin. When cancer spread to other parts of the body it is called metastatic.
In this study, researchers looked at how these drugs work in the human body. Researchers did medical tests on men and women before and after they took the drug. They wanted to know if there were:
• Any chemical changes in blood or urine, and
• Any unwanted side effects of the drug
• If the drug made the immune system work
This trial did not test if the drug helps to improve health.
4. What patients/people were included in this study
4.1 the number of subjects included in the trial by country both within and outside of the EU This trial included patients that had been diagnosed with advanced cutaneous melanoma cancer (skin cancer) and who had not received prior anti-cancer treatment for it.
The patients also had to be willing to provide a fresh sample of their tumour for researchers to be able to make the drug and had to have at least 1 tumour that could be measured by the doctor and did not have other major health concerns.
Patients could not participate if:
- they had received any previous treatment with a type of medication known as a checkpoint inhibitor or any medication that was designed to treat cancer by stimulating the immune system
- had any other type of cancer that was getting worse or needed a different type of treatment
- they were taking a drug that suppressed the immune system
Patients with lung cancer could be included but none participated in the trial.
In total, 7 patients with skin cancer participated in the study in the following countries: Belgium, Spain and the United Kingdom (UK).
• In Belgium 5 out of 7 patients were enrolled
• In Spain 2 out of 7 patients were enrolled
• In the UK no patients were enrolled
Although 7 patients were enrolled into the study only 6 received treatment, 4 men and 2 women. This was due to one patient’s cancer worsening before they received treatment.
The patients treated were aged between 62 years and 88 years of age.
5. Which medicines were studied?
Nous-PEV was made specifically for each patient. This means that each patient agreed to give a sample of their own tumour for a genetic analysis. The specific alterations in the tumour were identified and used to produce two products, known by their laboratory codes as GAd-PEV and MVA-PEV. Together they are known as NOUS-PEV. When given to the patients, Nous-PEV can help the body’s immune system to fight against the tumour cells.
The study was divided in 3 phases:
1. Screening phase: from when the patients signed the consent form until the day before they received the first study treatment;
2. Treatment phase: from when the patients received the first study treatment (pembrolizumab) until the day the last study treatment (pembrolizumab or Nous-PEV) was given. The treatment phase had 2 main parts:
a. Induction phase: the patients received only a product that is already used to treat this type of cancer (pembrolizumab). This was given, through a vein over 30 minutes, 3 times, every 21 days.
b. Nous-PEV phase: in addition to pembrolizumab, during this phase, the patients also received GAd-PEV and MVA-PEV. GAd-PEV was given once as an injection into the arm. MVA-PEV was given 3 times during the study, also as an injection. All patients received pembrolizumab throughout the study for a maximum of 105 weeks (35 cycles).
Patients received study treatments until their cancer got worse, or they had serious medical problems that did not allow them to continue treatment with the study drugs, or by their choice.
3. Survival follow-up phase: after the end of treatment, doctors monitored the patients to see if the cancer had returned or if they were staying healthy and for how long they lived, for up to a total of 2 years.6. What were the side effects
Side effects are negative or unwanted reactions that happen as a result of taking a medication or using a product. For example, feeling dizzy or having a headache. It is important for doctors to know about them to report if he believes the side effects are related to the treatment in the trial. A side effect is considered serious when it is life-threatening, needs hospital care, or causes lasting problems.
Serious and common side effects observed in this study are listed below.
2 out of 6 participants (33.3%) reported 1 serious side effect each:
- One patient had moderate “vertigo”, a condition in which you feel that you or your surroundings are spinning or moving when they actually aren’t. This can make normal activities, like walking or standing, feel difficult.
- one patient had moderate “hydronephrosis”. This is a condition where one or both kidneys swell up because urine can’t drain properly. Normally, urine flows from the kidneys to the bladder, but if something blocks this flow, it can cause the kidney to become enlarged and possibly damaged.
According to the doctor’s evaluation, none of these serious side effects were believed to be related to the medications given.
There were no deaths during the study due to side effects. However, one patient died during the survival follow-up phase, because their cancer got worse.
All patients who took part in this study had at least 1 side-effect. Due to the small number of patients in the study it is not possible to give the side-effects as a number. The most frequent side-effects seen with the treatment with all products were:
• High blood pressure
• Itchiness of the skin
• Shortness of breath
• Back pain
• Breakdown of damaged skeletal muscle
• Dizziness
• Cough
• Feeling of exhaustion, tiredness or not feeling well
• Pain and redness of the skin where the injection was done
• an increase in a pancreatic enzyme (lipase) which helps the liver breakdown fats from the diet.
Most of these side effects (80.8%) were related to the treatment with pembrolizumab, and some were related to the treatment with NOUS-PEV.
7. What were the overall results of the study?
To learn more about the safety of taking the study treatment (Nous-PEV) and pembrolizumab together, the study doctors looked at the number of certain side effects possibly caused by the study drugs in 3 patients, during the first 28 days after the study treatment was given. Because none of the specific side effects occurred, a further 4 patients were treated.
The sponsor decided to end the trial after a total of 7 patients volunteered to participate because given the study treatment in combination with pembrolizumab was shown to be safe and well tolerated. The decision to stop the study was made by the sponsor because of planning reasons and had nothing to do with any concerns about the safety of the product.
The patients who received all the products as described in the protocol were shown to have their immune system create a response to the injections.
8. How has this study helped patients and researchers?
The first results show that NOUS-PEV could be a helpful treatment for advanced skin cancer that can't be removed by surgery. These results suggest that it is worth looking at continuing the development NOUS-PEV, but more studies are needed to confirm how well it works and to see how it might help with other types of cancer.
9. Are there plans for further studies
No further clinical trials are planned at this point in time.
10 Where can I find more information about this study Further information about this study can be found in:
Study Details | Nous-PEV: a Novel Immunotherapy for Lung Cancer and Melanoma | ClinicalTrials.govREC name
South Central - Oxford A Research Ethics Committee
REC reference
20/SC/0417
Date of REC Opinion
15 Jan 2021
REC opinion
Further Information Favourable Opinion