TEIPP Immunotherapy in Patients With NSCLC

NCT05898763 | Completed Phase 1 DMC

• 1 other identifier: NL75654.000.20
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

In this multicenter, open label non-randomized phase I/II dose escalation study with extension cohort HLA-A\*0201-positive patients with non small cell lung cancer (NSCLC) can be included. The primary aim of this study is determine the safety, tolerability and immune modulating effects of the therapeutic LRPAP1 synthetic long peptide (LRPAP7-30V-SLP) vaccine (TEIPP24) at different doses. Secondary objectives are to assess the specificity and immune modulatory effects of the vaccine, to assess the antigen and immune status of the patients, and to determine progression free survival (PFS), overall survival (OS), and the radiological tumor response up to one year after first vaccination.

Conditions

Non Small Cell Lung Cancer

Keywords

Immunotherapy; Palliative treatment; Dose-escalation study; Checkpoint inhibitor

Outcome Measures

Primary Outcomes (3)

• Safety assessment based on the incidence rate of serious adverse drug reactions (ADR) as assessed by NCI-CTCAE version 5.0.

  Safety of the therapeutic LRPAP1 synthetic long peptide ( LRPAP7-30V-SLP) vaccine (TEIPP24) determined by the incidence rate at each dose level based on the following safety parameters: adverse drug reactions (ADR) and serious ADRs, changes in haematology and chemistry values, including those associated with hepatic and renal function, and assessment of physical examinations, vital signs and performance status. NCI-CTCAE version 5.0 will be used.

  Week 8 (two weeks after the third TEIPP24 vaccination)

• Tolerability assessment based on patients' tolerability of adverse drug reactions (ADR)

  Tolerability of the therapeutic LRPAP1 synthetic long peptide ( LRPAP7-30V-SLP) vaccine (TEIPP24) determined by patients' tolerability of ADRs. NCI-CTCAE version 5.0 will be used.

  Week 8 (two weeks after the third TEIPP24 vaccination)

• Immunogenicity assessed by HLA-A*0201-restricted LRPAP21-30 -specific CD8+ T-cell reactivity

  HLA-A\*0201-restricted LRPAP21-30 -specific CD8+ T-cell reactivity will be determined by measuring the magnitude and function of HLA-A\*0201-restricted LRPAP21-30 -specific CD8+ Tcells present in the blood and/or tumor samples before and after TEIPP24 vaccination at different dose levels.

  Week 3-6-9 (three weeks after every TEIPP24 vaccination)

Secondary Outcomes (5)

• The specificity and immune modulatory effect of the vaccine, determined by isolating LRPAP(21-30V)-specific CD8+ T cells

  Week 3-6-9 (three weeks after every TEIPP24 vaccination)

• Immunohistochemical staining of tumor material

  Before (week 0) and after treatment (week 9)

• Progression free survival (PFS)

  From week 0 up to week 52

• Overall survival (OS)

  From week 0 up to week 52

• Radiological tumor response

  From week 0 up to week 52

Study Arms (1)

Treatment arm

EXPERIMENTAL

Patients will be vaccinated with the TEIPP24 vaccine in Montanide ISA 51 every three weeks for a total of three rounds of vaccination. The total treatment duration is 9 weeks for each patient. The three dose levels tested are 20, 40 and 100 µg of peptide. Dose 1: 20 µg of peptide in Montanide ISA 51; Dose 2: 40 µg of peptide in Montanide ISA 51; Dose 3: 100 µg of peptide in Montanide ISA 51. Patients in the extension cohort will receive the highest safest dose of peptide in combination with pembrolizumab.

Drug: TEIPP24 (LRPAP7-30V-SLP vaccine in Montanide ISA-51)

Interventions

TEIPP24 (LRPAP7-30V-SLP vaccine in Montanide ISA-51) DRUG

Patients will receive three rounds of vaccination three weeks apart via one subcutaneous (SC) injection in an alternating limb. Patients in the extension cohort will receive the highest safest dose in combination with pembrolizumab (a CPI).These patients will receive three rounds of combination treatment with TEIPP24 vaccination and pembrolizumab every three weeks. Pembrolizumab will be administered as per standard of care.

Also known as: Pembrolizumab

Treatment arm

Eligibility Criteria

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

You may qualify if:

• Age \>18 years
• Pathologically and radiologically confirmed advanced NSCLC.
• Progression after minimally 4 cycles of combination platinum containing chemotherapy and immunotherapy (PD1), or after 4 cycles of platinum containing chemotherapy and immunotherapy (PD-1) followed by maintenance chemo immunotherapy
• HLA-A\*0201 positive
• An expected survival of at least 3 months
• WHO/ECOG performance status ≤ 2 (Appendix 3)
• Adequate renal function as defined by creatinine clearance \> 40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR)
• Adequate hepatic function as evidenced by
• Serum total bilirubin ≤ 2.5 × upper limit of normal (ULN) unless considered due to hepatic metastases
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3.0 × ULN, unless considered due to hepatic metastases
• Ability to return to the hospital for adequate follow-up as required by this protocol.
• Written informed consent according to International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) .

You may not qualify if:

• Current use of steroids (or other immunosuppressive agents). Patients must have had 6 weeks of discontinuation and must stop any such treatment during the time of the study. Prophylactic usage of dexamethasone during chemotherapy is excluded from this 6 weeks interval.
• Concomitant participation in another clinical intervention trial (except participation in a biobank study).
• Pregnant or lactating women.
• Known allergy to any of the ingredients of the vaccine (peptide, Montanide ISA-51, trifluoroacetic acid, acetonitrile, dichloromethane, dimethylsulfoxide).
• Any medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to give informed consent or participate in the study
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Patients with a currently active second malignancy. However, patients with the following history/concurrent conditions are allowed: Basal or squamous cell carcinoma of the skin; Carcinoma in situ of the cervix; Carcinoma in situ of the breast; Incidental histologic finding of prostate cancer.

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (2)

Leiden University Medical Center

Leiden, South Holland, 2333ZA, Netherlands

Location

Erasmus Medical Center

Rotterdam, South Holland, 3000 CA, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

montanide ISA 51; pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator (MD PhD)

Model Details: A multicenter, open label non-randomized phase I/II dose escalation study with extension cohort

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: June 12, 2023
• Study Start: September 29, 2021
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)