Study of Subcutaneous Pembrolizumab versus Intravenous Pembrolizumab, Given with Chemotherapy, to Treat Metastatic Squamous or Non Squamous Non-Small-Cell Lung Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Jul 2021 → ongoing

Decision date (initial)

2024-03-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-508308-40-00

EudraCT number

2020-002729-27

WHO UTN

U1111-1298-0215

ClinicalTrials.gov

NCT04956692

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Safety, Pharmacokinetic, Therapy

1. To compare AUC between pembrolizumab SC vs pembrolizumab IV.
2. To compare Ctrough between pembrolizumab SC vs pembrolizumab IV

Secondary objectives 7

1. To evaluate pembrolizumab SC and pembrolizumab IV with respect to ORR per RECIST 1.1 as assessed by blinded independent central review (BICR).
2. To evaluate exposure of pembrolizumab SC compared to pembrolizumab IV.
3. To evaluate the safety and tolerability of pembrolizumab SC compared to pembrolizumab IV.
4. To evaluate pembrolizumab SC and pembrolizumab IV with respect to PFS per RECIST 1.1 as assessed by BICR.
5. To evaluate pembrolizumab SC and pembrolizumab IV with respect to OS.
6. To evaluate pembrolizumab SC and pembrolizumab IV with respect to DOR per RECIST 1.1 as assessed by BICR.
7. To evaluate the development of ADAs following administration of pembrolizumab SC compared to pembrolizumab IV.

Conditions and MedDRA coding

Metastatic (stage IV) squamous or nonsquamous non-small cell lung cancer (NSCLC).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Has pathologically (histologically or cytologically) confirmed diagnosis of squamous or nonsquamous non-small cell lung cancer (NSCLC)
2. Has Stage IV (T any, N any, M1a, M1b, or M1c - American Joint Committee on Cancer 8th Edition) squamous or nonsquamous NSCLC
3. Has confirmation that epidermal growth factor receptor (EGFR), Anaplastic lymphoma kinase (ALK), or Receptor Tyrosine Kinase 1 (ROS1)-directed therapy is not indicated in nonsquamous NSCLC as well as mixed nonsquamous/squamous NSCLC. Participants with purely squamous NSCLC do not require testing
4. Has not received prior systemic treatment for their metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease
5. Has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 or 1
6. Male participants are eligible to participate if they agree to use contraception as per protocol unless confirmed to be azoospermic
7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees of using a contraceptive method per protocol
8. Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology
9. Submit an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated for PD-L1 status determination prior to randomization
10. Has adequate organ function

Exclusion criteria 19

1. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
2. Has known central nervous system (i.e., brain and/or spinal cord) metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate only if they satisfy all of the following: a) Have no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging performed at least 4 weeks after pretreatment brain imaging, and b) Are neurologically stable without the need for steroids for at least 14 days before first dose of trial treatment as per local site assessment
3. Has severe hypersensitivity to study intervention and/or any of its excipients
4. Has an active autoimmune disease that has required systemic treatment in past 2 years
5. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
6. Has an active infection requiring systemic therapy
7. Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B infection or known active Hepatitis C infection
8. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
9. Has symptomatic ascites or pleural effusion. A participant who is clinically stable after treatment for these conditions is eligible
10. Before the first dose of study intervention: a) Has received prior systemic cytotoxic chemotherapy for metastatic NSCLC b) Has received antineoplastic biological therapy for metastatic NSCLC c) Has had major surgery (<3 weeks prior to first dose) d) Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
11. Received radiation therapy to the lung that is >30 Gray within 6 months of the first dose of study intervention
12. Is expected to require any other form of antineoplastic therapy while on study
13. For participants with nonsquamous histology: Is unable to interrupt aspirin or other Non-steroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g/day, for a 5-day period
14. For participants with nonsquamous histology: Is unable or unwilling to take folic acid or vitamin B12 supplementation
15. Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis. Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease
16. Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention
17. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
18. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
19. Has had an allogenic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab at Cycle 1
2. Cycle 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab

Secondary endpoints 12

1. Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
2. Observed Ctrough of Pembrolizumab at the End of Cycle 1
3. Maximum Concentration (Cmax) of Pembrolizumab at Cycle 1
4. AUC 0-3wks of Pembrolizumab at Cycle 6
5. Cmax of Pembrolizumab at Cycle 6
6. Observed Ctrough of Pembrolizumab at the End of Cycle 6
7. Number of Participants Who Experienced an Adverse Event (AE)
8. Number of Participants Who Discontinued Study Treatment Due to an AE
9. Progression-Free Survival (PFS) per RECIST 1.1 as Assessed by BICR
10. Overall Survival (OS)
11. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
12. Anti-Drug Antibodies (ADAs) Incidence After Administration of Pembrolizumab

Investigational products

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

Test 1

Comparator 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Sung Jin (Laura) Kim

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Sung Jin (Laura) Kim

Third parties 7

Locations

5 EU/EEA countries · 26 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 74 files

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

Application history

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