Pembrolizumab With or Without Maintenance MK‑2870 in Metastatic Squamous 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 Sep 2024 → ongoing

Decision date (initial)

2024-08-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-510128-66-00

WHO UTN

U1111-1301-2790

ClinicalTrials.gov

NCT06422143

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Pharmacoeconomic, Pharmacokinetic, Pharmacodynamic

To compare pembrolizumab with or without maintenance MK-2870 with respect to OS

Secondary objectives 4

1. To compare pembrolizumab with or without maintenance MK-2870 with respect to PFS per RECIST 1.1 as assessed by BICR
2. To evaluate the safety and tolerability of all treatment arms
3. To evaluate the mean change from baseline in global health status/QoL, dyspnea, cough, and chest pain for pembrolizumab with or without maintenance MK-2870
4. To evaluate the TTD in global health status/QoL, dyspnea, cough, and chest pain for pembrolizumab with or without maintenance MK-2870

Conditions and MedDRA coding

Participants with treatment-naïve metastatic squamous Non-small Cell Lung Cancer (NSCLC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histologically or cytologically confirmed diagnosis of squamous non-small cell lung cancer (NSCLC) (Stage IV: M1a, M1b, M1c, American Joint Committee on Cancer Staging Manual, version 8).
2. Measurable disease per response evaluation criteria in solid tumors (RECIST) 1.1 as assessed by the local site investigator/radiology.
3. Life expectancy of at least 3 months.
4. Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 assessed within 7 days before allocation.
5. Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided.
6. Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
7. 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 before allocation.
8. Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
9. Participants who have adverse events (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). Note: Participants with Grade =2 neuropathy are eligible.
10. Has adequate organ function.
11. For Maintenance only (prior to randomization): is without disease progression of their NSCLC, as determined by blinded independent central review (BICR) using RECIST 1.1 after completion of study-specified Induction with an evaluable scan at Week 12 or most recent scan before randomization.
12. For Maintenance only (prior to randomization): has ECOG PS of 0 or 1 as assessed at the Prerandomization Visit.
13. For Maintenance only (prior to randomization): all AEs (with the exception of alopecia, Grade 2 fatigue, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement) have recovered.

Exclusion criteria 21

1. Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
2. History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
3. Active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea).
4. 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 corrected QT interval by Fridericia (QTcF) interval to >480 ms, and other serious cardiovascular and cerebrovascular diseases within 6 months before study intervention.
5. HIV-infected participants who have been newly diagnosed or with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.
6. Received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as a part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.
7. Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti programmed cell death ligand 2 (PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T lymphocyte-associated protein 4, OX-40, CD137). Note: Prior treatment with an anti-PD-1 or anti-PD-L1 agent for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.
8. Received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC).
9. Received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention.
10. Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
11. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
12. Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
13. Received prior treatment with a topoisomerase I inhibitor-containing ADC.
14. Is currently receiving a strong inducer/inhibitor of Cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study. The required washout period before starting MK-2870 is 2 weeks.
15. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
16. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
17. Severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients or to another biologic therapy.
18. Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
19. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
20. Active infection requiring systemic therapy.
21. History of allogeneic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS)

Secondary endpoints 11

1. Progression-Free Survival (PFS)
2. Number of Participants With One or More Adverse Events (AEs)
3. Number of Participants Discontinuing from Study Therapy Due to AE(s)
4. Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Global health status/Quality of Life (QoL) Score (EORTC QLQ-C30 Items 29 and 30)
5. Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Dyspnea (EORTC QLQ-C30 Item 8)
6. Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Cough (EORTC QLQ-LC13 Item 31)
7. Change in Score from Baseline to a Predefined Timepoint in Participant-Reported Chest Pain (EORTC QLQ-LC13 Item 40)
8. Time to First Deterioration (TTD) in Global Health Status/QoL Scores (EORTC QLQ-C30 Items 29 and 30)
9. TTD in Dyspnea Score (EORTC QLQ-C30 Item 8)
10. TTD in Cough Score (EORTC QLQ-LC13 Item 31)
11. TTD in Chest Pain Score (EORTC QLQ-LC13 Item 40)

Investigational products

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

Test 2

Auxiliary 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Niyati Bhagwati

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Niyati Bhagwati

Third parties 11

Locations

10 EU/EEA countries · 63 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 83 files

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

Application history

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