AST-VAC2 Vaccine in Patients With Non-small Cell Lung Cancer

This clinical study is looking at a vaccine called AST-VAC2 in adult patients with advanced non-small cell lung cancer (NSCLC). The main aim of the study: If the dose can be given safely to patients, learn more about the potential side effects of the vaccine and how they can be managed and also what happens to AST-VAC2 inside the body.

This clinical study is looking at a vaccine called AST-VAC2. AST-VAC2 has been designed to potentially help the immune system attack the cancer. This is a new vaccine which looks promising in laboratory studies but it has never been tested in man.

Dendritic cells occur naturally in your body as part of the immune system however these dendritic cells have a special role in finding proteins in the body which are associated with cancer and it is hoped that the vaccine will train the immune system to recognise these proteins and attack the cancer.

Some cancers tend to have more of a certain type of protein (part of the body's building blocks that make up cells) called 'hTERT' and it has been shown in laboratory studies (and also studies in patients using a similar type of vaccine), that targeting hTERT can lead to destruction of cancer cells by the immune system. AST-VAC2 will target the hTERT protein.

Human Leukocyte Antigen (HLA) is another type of protein. An HLA pre-screening test will be able to show if a person is positive or negative for a specific HLA protein (AST-VAC2 can only work with some types of HLA), as being positive for the protein may mean there is a better chance of the vaccine attacking the cancer. Patients who are positive for the specific HLA type will be asked to consent to the vaccine. Those patients who are negative for the HLA type will not be eligible for the trial.

Eligibility Criteria:
Inclusion Criteria:

1. a) Patients with advanced NSCLC (metastatic or locally advanced), for whom there are no other suitable treatment options.-

   * Able to and likely to be well enough to receive six vaccinations i.e. judged by the Investigator to not require alternate treatment for the duration of the vaccination schedule and period to end of vaccination visit.
   * Has had sufficient wash out periods from previous treatments as follows:

     i) four weeks for chemotherapy ii) six weeks for investigational medicinal products (IMPs) iii) eight weeks for immunotherapy (shorter intervals may be acceptable based on half-life of treatment. Eligibility will be confirmed by the Sponsor and CI).
   * Measurable disease
   * Biopsiable disease is preferable however patients without biopsiable disease can still be considered for the study.
2. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
3. Confirmed HLA A\*02:01 positive genotype.
4. Life expectancy of at least 12 weeks.
5. World Health Organisation (WHO) performance status of 0-2.
6. Haematological and biochemical indices within the ranges shown below. These measurements must be performed prior to the patient receiving the first AST-VAC2 vaccination.

   Laboratory Test and Value required

   Haemoglobin (Hb) ≥9.0 g/dL; Absolute neutrophil count (ANC) ≥1.5 x 10\^9 /L; Platelet count ≥100 x 10 \^9/L; Lymphocyte count ≥1.0 x 10\^9 /L; Bilirubin ≤1.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤ 3.0 x ULN; Calculated creatinine clearance \> 30 mL/min
7. 18 years or over at the time consent is given.

Exclusion Criteria:

1. Radiotherapy (except for palliative reasons) during the previous four weeks before treatment.
2. Ongoing toxic manifestations of previous treatments greater than CTCAE Grade 1. Exceptions to this are alopecia or certain Grade 2 toxicities, which in the opinion of the Investigator and the Sponsor should not exclude the patient.
3. Systemic steroids or other drugs with a likely effect on immune competence are forbidden during the trial with the exception of replacement treatment. Inhaled and topical steroids are permitted. The predictable need of their use will preclude the patient from trial entry.
4. Female patients who are able to become pregnant (or are already pregnant or lactating). However, those patients who have a negative serum or urine pregnancy test before enrolment and agree to use two forms of contraception (one effective form plus a barrier method) \[oral, injected or implanted hormonal contraception and condom; intra-uterine device and condom; diaphragm with spermicidal gel and condom\] or agree to sexual abstinence\*, effective from the first administration of AST-VAC2 throughout the trial and for six months afterwards are considered eligible.
5. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using a barrier method of contraception \[condom plus spermicide\] or to sexual abstinence\* effective from the first administration of AST-VAC2, throughout the trial and for six months afterwards. Men with partners of child-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intrauterine device, diaphragm with spermicidal gel or sexual abstinence). Men with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure of the foetus or neonate.

   \*Abstinence is only considered to be an acceptable method of contraception when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
6. Major thoracic or abdominal surgery from which the patient has not yet recovered.
7. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
8. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
9. Evidence of any ongoing active autoimmune disease.
10. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association \[NYHA\]), prior history of cardiac ischaemia or prior history of cardiac arrhythmia.
11. Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase I trial of AST-VAC2. Participation in an observational trial or interventional clinical trial which does not involve administration of an IMP and which would not place an unacceptable burden on the patient in the opinion of the Investigator and Medical Advisor would be acceptable.
12. Any vaccination given within four weeks before the first AST-VAC2 vaccination (except for COVID-19 vaccinations which are permitted at investigators discretion).
13. Any planned prophylactic vaccination from trial entry until completion of the AST-VAC2 vaccinations (except for COVID-19 vaccinations which are permitted at investigators discretion).
14. Any condition which might interfere with the patient's ability to generate an immune response.
15. Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.