Efficacy and safety of UV1 vaccination +/- standard of care as first line treatment of patients with non-small cell lung cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vestre Viken HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Aug 2022 → 12 Sep 2024

Decision date (initial)

2023-08-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ultimovacs ASA

External identifiers

EU CT number

2022-502437-25-00

EudraCT number

2021-005729-25

ClinicalTrials.gov

NCT05344209

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

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

Secondary objectives 3

1. To compare overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to response (TTR) and duration of response (DOR) according to Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1), in patients who receive PD-1/PD-L1 inhibitor treatment with patients who receive PD-1/PD-L1 inhibitor treatment in combination with UV1 vaccination.
2. To determine the safety and tolerability in patients who receive PD-1/PD-L1 inhibitor treatment compared to patients who receive PD-1/PD-L1 inhibitor treatment in combination with UV1 vaccination.
3. To investigate possible biological markers for response, resistance and toxicity

Conditions and MedDRA coding

advanced or metastatic non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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 PD-1/PD-L1 inhibitor monotherapy in the first-line setting
2. 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
3. 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
4. Available unstained archived tumour tissue sample in sufficient quantity to allow for analyses. At least fifteen unstained slides or a tumour block (preferred)
5. Male and female age ≥ 18 years at time of signing the ICF
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
7. 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) Females: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) x 0.85 72 x serum creatinine (mg/dL)
8. Written informed consent obtained prior to any study specific procedure

Exclusion criteria 17

1. Previous treatment with a PD-1 or PD-L1 inhibitor, or any other agent targeting immune checkpoints
2. 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
3. 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 randomization.
4. Known history of leptomeningeal carcinomatosis
5. Uncontrolled seizures.
6. Current or prior use of immunosuppressive medication within 28 days before the first dose of PD-1/PD-L1 inhibitor, 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
7. 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
8. History of primary immunodeficiency
9. History of allogeneic organ transplant
10. 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
11. 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
12. Pregnant or lactating women
13. Live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving PD-1/PD-L1 inhibitor
14. 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
15. History of allergy or hypersensitivity to any of the active substances or excipients in the study drug
16. Involvement in the planning and/or conduct of the study (investigator staff and/or staff at the study site)
17. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) as determined by Blinded Independant Central Review (BICR)

Secondary endpoints 5

1. Overall Survival (OS)
2. Objective Response Rate (ORR)
3. Disease Control Rate (DCR)
4. Time To Recurrence (TtR)
5. Duration of Response (DoR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vestre Viken HF

Sponsor organisation

Vestre Viken HF

Address

Groenland 32

City

Drammen

Postcode

3045

Country

Norway

Scientific contact point

Organisation

Vestre Viken HF

Contact name

Odd Terje Brustugun

Public contact point

Organisation

Vestre Viken HF

Contact name

Odd Terje Brustugun

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications