Pembrolizumab Alone versUs pembrolizumab-chemotherapy in first LInE NSCLC (PAULIEN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Amsterdam UMC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Neoplasms [C04]

Trial duration

completed 17 Jan 2025

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516581-11-00

EudraCT number

2019-002743-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To assess the effect of chemotherapy given concurrently with pembrolizumab on overall response rate (ORR) in NSCLC patients with high PD-L1 and high tumor burden

Secondary objectives 2

1. To examine the effect of chemotherapy given concurrently with pembrolizumab on progression free survival (PFS) and overall survival (OS) in patients with high PD-L1 and high tumor burden as compared to pembrolizumab monotherapy followed by chemotherapy at progression
2. To compare the PFS of concurrent chemo-pembrolizumab with sequential pembrolizumab followed by chemotherapy at progression (i.e. PFS-1 plus PFS-2)

Conditions and MedDRA coding

Advanced stage NSCLC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Histologically confirmed NSCLC, negative for EGFR mutations and ALK fusions, no molecular testing is required in squamous NSCLC
2. ECOG Performance Scale 0-2
3. Be willing and able to provide written informed consent for the trial
4. Be 18 years or older of age on the day of signing informed consent
5. Have measurable disease based on RECIST v1.1
6. Must provide tissue from a histological tumor biopsy that was not yet irradiated
7. High tumor PD-L-1 expression (≥50% TPS)
8. High tumor burden (metastases (M1)) and not amenable for local consolidative therapies
9. Must have adequate hematologic and organ function

Exclusion criteria 9

1. Patients amenable for local consolidative therapies
2. Use of steroids equivalent to >10 mg prednisolon per day prior to start of study or other immunosuppressive medications within 14 days prior. Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
3. Untreated brain metastases
4. Uncontrolled active infections, HIV, active Hepatitis B or C
5. Autoimmune diseases and interstitial lung diseases are to be excluded depending on physicians decision
6. A known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
7. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
8. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening.
9. Prior systemic therapy for the NSCLC using chemotherapy or immunotherapy with prior therapy 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 immune checkpoint pathways.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. ORR, as defined by partial response (PR) and complete response (CR) at week 6
2. Disease control rate (DCR), as defined by stable disease (SD) and PR and CR at week 6

Secondary endpoints 5

1. PFS, as determined using Response Evaluation Criteria in Solid Tumors (RECIST1.1) and defined as time to the development of new lesions, progression of existing lesions, or death, whichever comes first.
2. PFS-2, as defined by the PFS on second line chemotherapy in arm 1.
3. ORR-2, as defined by the ORR on second line chemotherapy in arm 1.
4. Overall Survival (OS). Time frame: Baseline until death.
5. Safety defined as the percentage of patients with adverse events. Adverse events will be defined as described in the Common Terminology Criteria for Adverse Events (CTCAE).

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Amsterdam UMC

Sponsor organisation

Stichting Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Stichting Amsterdam UMC

Contact name

Idris Bahce

Public contact point

Organisation

Stichting Amsterdam UMC

Contact name

Idris Bahce

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

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

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