Dose tapering and Early Discontinuation to InCreAse cosT-effictIveness Of immunotherapy for Non-small cell lung carcinoma trial number 1 (NVALT-30 - Dedication-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud universitair medisch centrum

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

10 Sep 2024 → ongoing

Decision date (initial)

2024-09-10

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516195-15-00

EudraCT number

2020-000493-15

ClinicalTrials.gov

NCT04909684

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic

To investigate the non-inferiority of reduced dose versus standard of care dose of pembrolizumab for treatment of advanced stage NSCLC in terms of overall survival.

Secondary objectives 2

1. To develop immune checkpoint inhibitor response biomarkers.
2. To study possible effects from co-medication on treatment outcome.

Conditions and MedDRA coding

Advanced NSCLC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
2. Participants must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
3. Subjects with cytologically or histologically confirmed advanced stage or recurrent NSCLC (per the 8th International Association for the Study of Lung Cancer classification), eligible for treatment with pembrolizumab in line with ESMO guidelines.
4. Known PD-L1 status (performed on cytology or histology).
5. Subjects are aged ≥ 18 years.
6. Women must not be breastfeeding.
7. Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of 5 months (30 days of ovulatory cycle plus the time required for the investigational drug to undergo five half-lives) after end of pembrolizumab treatment.
8. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of 7 months (90 days plus the time required for pembrolizumab to undergo five half-lives) after the last dose of investigational drug. In addition, male participants must be willing to refrain from sperm donation during this time.

Exclusion criteria 10

1. Subjects with symptomatic untreated CNS metastases are excluded. i) Subjects are eligible if CNS metastases are asymptomatic or adequately treated and neurological symptoms have returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrolment. ii) In addition, participants must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to treatment assignment.
2. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrolment. Inhaled or topical steroids, and steroids for adrenal replacement therapy are permitted.
3. A known CD4+ T-cell count of less than 100 cells/μL (CD4+ T cell count measurement is not required for patients without a history of low CD4+ T cell counts or HIV).
4. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
5. Treatment with adjuvant or neoadjuvant chemotherapy 3 months prior to enrolment.
6. Non-palliative treatment with chemoradiation for locally advanced disease 3 months prior to enrolment. Palliative radiotherapy is allowed any time.
7. Women of childbearing potential (WOCBP) with a known pregnancy or a positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) prior to the start of study treatment.
8. History of allergy or hypersensitivity to study drug components.
9. Subjects may not have previously received a solid organ transplantation.
10. Total body weight <40 or >140 kg.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary study parameter is the overall survival rate at one year.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud universitair medisch centrum

Sponsor organisation

Stichting Radboud universitair medisch centrum

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

Demi Peeters

Public contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

Demi Peeters

Locations

1 EU/EEA country · 30 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 7 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