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

Inclusion Criteria

• 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.
• Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
• Confirmed HLA A*02:01 positive genotype.
• Life expectancy of at least 12 weeks.
• World Health Organisation (WHO) performance status of 0-2.
• 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

• 18 years or over at the time consent is given.

Exclusion Criteria

• Radiotherapy (except for palliative reasons) during the previous four weeks before treatment.
• 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.
• 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.
• 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.
• 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.

• Major thoracic or abdominal surgery from whi