Efficacy and Safety of Anti-PD-1/PD-L1 Treatment +/- UV1 Vaccination in Patients With Non-small Cell Lung Cancer

NCT05344209 | Recruiting Phase 2

• 1 other identifier: LUNGVAC
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

A Randomized, Multicenter Study Investigating Efficacy and Safety of anti-PD-1/PD-L1-treatment +/- UV1 vaccination as first line treatment in patients with inoperable advanced or metastatic non-small cell lung cancer. The objective of the phase 2 study is to induce a meaningful Progression-Free Survival (PFS) benefit in patients with stage IIIB/IIIC or stage IV NSCLC by treating with anti-PD-1/PD-L1 treatment and UV1 vaccination versus anti-PD-1/PD-L1 treatment alone.

Conditions

Oncology; NSCLC Stage IV; NSCLC, Stage III

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) as determined by Blinded Independent Central Review (BICR)

  Evaluate and compare the efficacy of anti-PD-1/PD-L1-treatment with or without UV1 vaccination in patients with stage IIIB/IIIC or stage IV NSCLC.

  Up to 2 years

Secondary Outcomes (2)

• Response evaluation

  Throughout trial (up to 2 years)

• monitoring AE

  continously and until 4 months after discontinuation of study treatment

Other Outcomes (3)

• molecular characterization and analyses

  up to 2 years

• immunophenotyping or characterization of the immune cell subsets in the periphery

  In biological samples collected at screening, visit 5/6, end-of-treatment, safety visit and first follow-up visit.

• To investigate the role of PET/CT in early response evaluation

  up to 2 years

Study Arms (2)

anti-PD-1/PD-L1 treatment + UV1 vaccination

EXPERIMENTAL

anti-PD-1/PD-L1 treatment + UV1 vaccination (and sagramostim)

Biological: UV1; Drug: Sagramostim; Drug: Anti-PD-1/PD-L1 treatment

anti-PD-1/PD-L1 treatment

OTHER

anti-PD-1/PD-L1 treatment

Drug: Anti-PD-1/PD-L1 treatment

Interventions

UV1 BIOLOGICAL

UV1 vaccine

anti-PD-1/PD-L1 treatment + UV1 vaccination

Sagramostim DRUG

for stimulation of local dendritic cell population to take up the vaccine and to mature into professional APCs

Also known as: leukine

anti-PD-1/PD-L1 treatment + UV1 vaccination

Anti-PD-1/PD-L1 treatment DRUG

either pembrolizumab, atezolizumab or cemiplimab

anti-PD-1/PD-L1 treatment; anti-PD-1/PD-L1 treatment + UV1 vaccination

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed NSCLC stage IIIB/IIIC or IV not amenable for curative treatment, with PD-L1 ≥ 50% measured by a validated method, and eligible for pembrolizumab monotherapy in the first-line setting
• At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline according to RECIST 1.1
• Subjects who received previous neo-adjuvant or adjuvant systemic therapy (other than immunotherapies) will be eligible if neo-adjuvant or adjuvant therapy was completed at least 12 months prior to the development of metastatic disease. Last dose of neoadjuvant or adjuvant therapy must be more than 12 months prior to enrollment/randomization
• Available unstained archived tumour tissue sample in sufficient quantity to allow for analyses. At least fifteen unstained slides or a tumour block (preferred)
• Male and female age ≥ 18 years at time of signing the ICF
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate organ function as defined below
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 x (\> 1500 per mm3)
• Platelet count ≥100 x 109/L (\>75,000 per mm3)
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
• Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL \>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)

You may not qualify if:

• Previous treatment with a PD-1 or PD-L1 inhibitor, including pembrolizumab or any other agent targeting immune checkpoints
• Previous malignancy (except non-melanoma skin cancer and the following in situ cancers: bladder, gastric, esophageal, colon, endometrial, cervical, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry
• Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids (prednisone \>10 mg or equivalent). Surgery, radiation and/or corticosteroids (any dose \>10 mg prednisone equivalent) must have been completed ≥ 2 weeks prior to registration
• Known history of leptomeningeal carcinomatosis
• Uncontrolled seizures.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of pembrolizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroid premedication given as prophylaxis for imaging contrast allergy should not be counted for this criterion
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome) within the past 2 years. Subjects with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded
• History of primary immunodeficiency
• History of allogeneic organ transplant
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• Active infection including tuberculosis (clinical evaluation including: physical examination findings, radiographic findings, positive PPD test, etc.), hepatitis B (known positive HBV surface antigen \[HBsAg\] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies as defined by a positive ELISA test). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. HIV testing is not required in the absence of clinical suspicion
• Pregnant or lactating women
• Live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving pembrolizumab
• Any condition that, in the opinion of the investigator, would interfere with the evaluation of study treatment or interpretation of patient safety or study results
• History of allergy or hypersensitivity to any of the active substances or excipients in the study drug

Sponsors & Collaborators

• Vestre Viken Hospital Trust: lead
• University Hospital, Akershus: collaborator
• Oslo University Hospital: collaborator
• Haukeland University Hospital: collaborator
• Helse Stavanger HF: collaborator
• Helse Fonna: collaborator
• Helse Nord-Trøndelag HF: collaborator
• St. Olavs Hospital: collaborator
• Alesund Hospital: collaborator
• Helse Forde: collaborator
• University Hospital of North Norway: collaborator

Study Sites (1)

Vestre Viken Health Trust

Drammen, Akershus, 3004, Norway

RECRUITING

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Colony-Stimulating Factors; sargramostim

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Odd Terje Brustugun, MD, PhD

  Vestre Viken Health trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Odd Terje Brustugun, Md, PhD

CONTACT

32804029; otr@vestreviken.no

Inger Johanne Zwicky Eide, MD

CONTACT

32802991; ingei@vestreviken.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Phase II, Open-label, Multicenter Study

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: April 25, 2022
• Study Start: August 12, 2022
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2027
• Last Updated: November 9, 2023

Record last verified: 2023-11

Locations

NO (1)