Pembrolizumab Monotherapy versus Sacituzumab Govitecan in Combination with MK‑3475 for PD-L1 TPS ≥50% Metastatic NSCLC

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

9 Feb 2023 → ongoing

Decision date (initial)

2023-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC · Gilead

External identifiers

EU CT number

2023-503501-11-00

EudraCT number

2022-000836-49

WHO UTN

U1111-1287-4239

ClinicalTrials.gov

NCT05609968

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

1. To compare pembrolizumab in combination with sacituzumab govitecan with pembrolizumab alone with respect to progression-free survival per RECIST 1.1 as assessed by blinded independent central review
2. To compare pembrolizumab in combination with sacituzumab govitecan with pembrolizumab alone with respect to overall survival

Secondary objectives 5

1. To compare pembrolizumab in combination with sacituzumab govitecan with pembrolizumab alone with respect to objective response rate per RECIST 1.1 as assessed by blinded independent central review
2. To evaluate duration of response per RECIST 1.1 by blinded independent central review for pembrolizumab in combination with sacituzumab govitecan and pembrolizumab alone
3. To evaluate the mean change from baseline (at randomization) in global health status/quality of life, physical functioning, role functioning, dyspnea, cough, and chest pain for pembrolizumab in combination with sacituzumab govitecan and pembrolizumab alone
4. To evaluate the time to deterioration in global health status/quality of life, physical functioning, role functioning, dyspnea, cough, and chest pain for pembrolizumab in combination with sacituzumab govitecan and pembrolizumab alone
5. To evaluate the safety and tolerability for pembrolizumab in combination with sacituzumab govitecan and pembrolizumab alone

Conditions and MedDRA coding

Metastatic Non-small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
2. Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase 1 (ALK-1), or ROS proto-oncogene 1 (ROS-1)-directed therapy is not indicated as primary therapy
3. Has provided tumor tissue that demonstrates PD-L1 tumor proportion score (TPS) ≥50% of tumor cells as assessed by immunohistochemistry (IHC) at a central laboratory
4. Has a life expectancy of at least 3 months

Exclusion criteria 20

1. Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
2. Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC
3. Has previously received treatment with Topoisomerase 1 inhibitors or Trop-2 targeted therapy
4. Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
5. Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids
6. Has received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study intervention
7. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
8. Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration
9. Has cardiac disease * Myocardial infarction or unstable angina pectoris within 6 months of enrollment * History of serious ventricular arrhythmia, high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications; history of QT interval prolongation * New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of <40%
10. Has active chronic inflammatory bowel disease
11. Has 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 medication
12. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab or sacituzumab govitecan and/or any of their excipients
14. Has active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy
15. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
16. Has active infection requiring systemic therapy
17. Has history of human immunodeficiency virus (HIV) infection
18. History of hepatitis B or known active hepatitis C virus infection
19. Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
20. Have not adequately recovered from major surgery or have ongoing surgical complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression-Free Survival (PFS)
2. Overall Survival (OS)

Secondary endpoints 16

1. Objective Response (OR)
2. Duration of Response (DOR)
3. Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30
4. Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
5. Change from Baseline in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30
6. Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30
7. Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC QLQ-LC13)
8. Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
9. Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30
10. TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
11. TTD in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30
12. TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30
13. TTD in Cough Score (Item 31) on the EORTC QLQ-LC13
14. TTD in in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
15. Number of Participants Who Experience an Adverse Event (AE)
16. Number of Participants Who Discontinue Study Treatment Due to an AE

Investigational products

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

Test 2

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

Renata Eiras Martins

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Renata Eiras Martins

Third parties 7

Locations

8 EU/EEA countries · 37 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 82 files

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

Application history

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