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

NCT03371485 | Completed Phase 1 Results DMC

• 2 other identifiers: CRUKD/17/0032016-002577-35
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Advanced Non-small Cell Lung Cancer

Keywords

Non-small cell lung cancer; Immunotherapy; Cancer vaccine; Dendritic cell vaccine; Allogeneic vaccine

Outcome Measures

Primary Outcomes (2)

• Frequency and Causality of Serious Adverse Events (SAEs), Non-Serious Adverse Events (NSAEs) and Grade ≥3 Adverse Events (AEs) to AST-VAC2

  Number of SAEs, NSAEs and Grade ≥3 AEs overall and number of SAEs, NSAEs and Grade ≥3 AEs related to AST-VAC2. AEs categorised according to Medical Dictionary for Regulatory Activities (MedDRA) version (v) 25.0 and graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.02 or protocol specific grading system for injection site reactions (ISRs; Section 9.8 of protocol). AEs assessed by the reporting study doctors for a causal relationship to AST-VAC2. Related are those AEs with a causality of possible, probable or highly probable. All AEs and SAEs were collected until 30 days post last vaccination but only related AEs and SAEs were collected thereafter.

  From the time of informed consent up to 2 years from the first dose of AST-VAC2, a median (range) of 402.5 days (101-770).

• Number of Participants Experiencing ISRs by Grade

  Number of participants experiencing ISRs Grade 1 to 4 according to protocol-specific grading of ISRs (protocol section 9.8); Grade 1: minimal effect on activities of daily living, Grade 2: restricts activities of daily living, Grade 3: prevents/severely limits activities of daily living, Grade 4: life-threatening consequences; urgent intervention indicated. Participants may have had ISRs of different grades at different vaccinations and are counted once for each grade of ISR reported.

  From the time of informed consent up to 2 years from the first dose of AST-VAC2, a median (range) of 402.5 days (101-770).

Secondary Outcomes (6)

• Number of Participants Showing a Durable Peripheral Immune Response

  Screening, vaccination weeks 3, 4 and 6; 2 weeks post last vaccination and 3, 6 and 12 months post first vaccination.

• Mean Fold Change in hTERT Specific T Cells Over Baseline by Timepoint: hTERT Peptide Pool 1 Assay (p1-387)

  Screening, vaccination weeks 3, 4 and 6; 2 weeks post last vaccination and 3, 6 and 12 months post first vaccination.

• Mean Fold Change in hTERT Specific T Cells Over Baseline by Timepoint: hTERT Peptide Pool 2 Assay (p377-763)

  Screening, vaccination weeks 3, 4 and 6; 2 weeks post last vaccination and 3, 6 and 12 months post first vaccination.

• Mean Fold Change in hTERT Specific T Cells Over Baseline by Timepoint: hTERT Peptide Pool 3 Assay (p753-1132)

  Screening, vaccination weeks 3, 4 and 6; 2 weeks post last vaccination and 3, 6 and 12 months post first vaccination.

• Tumour Response According to Immune-Related Response Criteria (irRC) Post Vaccination

  Radiological disease assessment at Baseline and End of Vaccination visit (30 days post last vaccination), up to 94 days.

Study Arms (1)

Participants with advanced NSCLC, to receive AST-VAC2

EXPERIMENTAL

Participants will receive up to a maximum of six vaccinations over six weeks. Each weekly AST-VAC2 vaccination will be administered as a split dose via two intradermal injections at a target dose defined as 1 x 10\^7 viable cells. There is no dose escalation planned during the study; only one dose level will be explored.

Biological: AST-VAC2

Interventions

AST-VAC2 BIOLOGICAL

Allogeneic dendritic cell vaccine.

Participants with advanced NSCLC, to receive AST-VAC2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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 which the patient has not yet recovered.
• At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
• Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
• Evidence of any ongoing active autoimmune disease.
• 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.
• 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.
• Any vaccination given within four weeks before the first AST-VAC2 vaccination (except for COVID-19 vaccinations which are permitted at investigators discretion).
• 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).
• Any condition which might interfere with the patient's ability to generate an immune response.

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (2)

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Links

• Simple summary of trial on Cancer Research UK website.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

An interim report presenting data for 2-year follow-up was planned as participants were to be followed-up for 5 years for safety. However, no participants continued beyond 2 years and end of trial was reached, so there will be no further data beyond the 2-year follow-up reported here. Due to difficulties in interpretation of non-durable response versus limitations of the ELISPOT assay, only durable response has been reported for clarity for outcome measure 5.

Results Point of Contact

• Title: Regulatory Affairs Manager
• Organization: Cancer Research UK Centre for Drug Development

regulatory@cancer.org.uk

+44 203 4696878

Study Officials

• Gary Middleton, Prof

  The Queen Elizabeth Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: December 13, 2017
• Study Start: May 29, 2018
• Primary Completion: August 8, 2022
• Study Completion: August 8, 2022
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)