Clinical trial comparing MK-2870 given with pembrolizumab to pembrolizumab alone in participants who have had surgery for 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

2 Oct 2024 → ongoing

Decision date (initial)

2024-05-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-508012-35-00

WHO UTN

U1111-1297-4260

ClinicalTrials.gov

NCT06312137

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Efficacy, Therapy, Safety, Pharmacogenomic, Pharmacokinetic, Pharmacoeconomic

To compare MK-2870 plus pembrolizumab versus pembrolizumab monotherapy with respect to DFS as assessed by BICR

Secondary objectives 6

1. To compare MK-2870 plus pembrolizumab to pembrolizumab monotherapy with respect to OS
2. To evaluate MK-2870 plus pembrolizumab and pembrolizumab monotherapy with respect to DMFS as assessed by the investigator
3. To evaluate MK-2870 plus pembrolizumab and pembrolizumab monotherapy with respect to DFS as assessed by the investigator
4. To evaluate MK-2870 plus pembrolizumab and pembrolizumab monotherapy with respect to LCSS
5. To evaluate the safety and tolerability of MK-2870 plus pembrolizumab
6. To evaluate MK-2870 plus pembrolizumab and pembrolizumab monotherapy with respect to mean change from baseline in global health status/QoL, physical functioning, role functioning, and lung cancer symptoms using the EORTC QLQ-C30 and EORTCQLQ-LC24

Conditions and MedDRA coding

Newly diagnosed NSCLC with resectable clinical Stage II, IIIA or IIIB (with nodal involvement [N2])

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Has histological or cytological confirmation of squamous or nonsquamous non-small cell lung cancer (NSCLC), resectable clinical Stage II, IIIA or IIIB (with nodal involvement [N2]) per AJCC eighth edition guidelines.
2. Has confirmation that either epidermal growth factor receptor (EGFR)-directed or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated as primary therapy
3. Is able to undergo surgery based on opinion of investigator after consultation with surgeon
4. Is able to receive neoadjuvant pembrolizumab and platinum-based doublet chemotherapy
5. Applies to screening for the adjuvant period only, before randomization: Has not achieved pathological complete response (pCR) at surgery by local review of pathology
6. Applies to screening for the adjuvant period only, before randomization: Tumor tissue sample from surgical resection has been provided for determination of programmed cell death ligand 1 (PD-L1) and trophoblast cell surface antigen 2 (TROP2) status by central vendor before randomization into the adjuvant period
7. Applies to screening for the adjuvant period only, before randomization: Confirmed to be disease-free based on re-baseline radiological assessment as documented by contrast enhanced chest/abdomen/pelvis computed tomography (CT) (or magnetic resonance imaging (MRI)) within 28 days before randomization
8. Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible
9. Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
10. Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load at screening
11. Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at least 4 weeks before the start of study intervention

Exclusion criteria 19

1. Has one of the following tumor locations/types: • NSCLC involving the superior sulcus • Large cell neuro-endocrine cancer (LCNEC) • Sarcomatoid tumor • Diagnosis of SCLC or, for mixed tumors, presence of small cell elements
2. Has Grade ≥2 peripheral neuropathy
3. Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
4. Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
5. Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QT corrected for heart rate by Fridericia's cube root formula (QTcF) interval to >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention
6. Has received prior neoadjuvant therapy for their current NSCLC diagnosis
7. Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
8. Has received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
9. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
10. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
12. Has a known additional malignancy that is progressing or has required active treatment within the past 5
13. Has an active autoimmune disease that has required systemic treatment in the past 2 years
14. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
15. Has an active infection requiring systemic therapy
16. Is an HIV-infected participant with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
17. Has a concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid (DNA)) and Hepatitis C virus (defined as anti-HCV antibody (Ab) positive and detectable HCV ribonucleic acid (RNA)) infection
18. Has a history of allogeneic tissue/solid organ transplant
19. Has not adequately recovered from major surgery or have ongoing surgical complications

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free survival (DFS) as assessed by Blinded Independent Central Review (BICR)

Secondary endpoints 12

1. Overall survival (OS)
2. Distant metastasis-free survival (DMFS) as assessed by investigator
3. DFS as assessed by investigator
4. Lung cancer specific survival (LCSS)
5. Number of participants who experience an Adverse Event (AE)
6. Number of participants who discontinue study intervention due to AEs
7. Change from Baseline in Global health status/Quality of Life (QoL) score (Quality of Life Questionnaire (QLQ)-C30 Items 29 and 30)
8. Change from Baseline in Physical functioning score (QLQ-C30 Items 1 to 5)
9. Change from Baseline in Role functioning score (QLQ-C30 Items 6 and 7)
10. Change from Baseline in Dyspnea scores (QLQ-C30 Item 8)
11. Change from Baseline in Coughing scores (QLQ-LC24 Items 31 and 52)
12. Change from Baseline in Chest pain scores (QLQ-LC24 Item 40)

Investigational products

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

Test 2

Auxiliary 9

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

Jongseok Kim

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Jongseok Kim

Third parties 9

Locations

13 EU/EEA countries · 96 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 156 files

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

Application history

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