A study of MK7684A versus Pembrolizumab in PD-L1 Positive Metastatic NSCLC (KEYVIBE-003)

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

21 Apr 2021 → 27 Jan 2026

Decision date (initial)

2023-10-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-505362-28-00

EudraCT number

2020-004049-35

WHO UTN

U1111-1291-5552

ClinicalTrials.gov

NCT04738487

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

1. To compare MK-7684A to pembrolizumab alone with respect to OS in participants with PD-L1 TPS ≥50%.

Secondary objectives 9

1. To compare MK-7684A to pembrolizumab alone with respect to OS in participants with PD-L1 TPS ≥1% and in participants with PD-L1 TPS 1% to 49%
2. To compare MK-7684A to pembrolizumab alone with respect to PFS per RECIST 1.1 by BICR in participants with PD-L1 TPS ≥50% and in participants with PD-L1 ≥1%
3. To compare MK-7684A to pembrolizumab alone with respect to PFS per RECIST 1.1 by BICR in participants with PD-L1 TPS 1% to 49%
4. To compare MK-7684A to pembrolizumab alone with respect to ORR per RECIST 1.1 by BICR in participants with PD-L1 TPS ≥1%
5. To compare MK-7684A to pembrolizumab alone with respect to ORR per RECIST 1.1 by BICR in participants with PD-L1 TPS ≥50% and in participants with PD-L1 TPS 1% to 49%
6. To evaluate DOR per RECIST 1.1 by BICR for MK-7684A compared to pembrolizumab alone in participants with PD-L1 TPS ≥50%, in participants with PD-L1 TPS 1% to 49% and in participants with PD-L1 TPS ≥1%
7. To evaluate the mean change from baseline in global health status/ QoL, physical functioning, role functioning, dyspnea, cough, chest pain for MK-7684A compared to pembrolizumab alone in participants with PD-L1 TPS ≥50%, in participants with PD-L1 TPS 1% to 49% and in participants with PD-L1 TPS ≥1%
8. To evaluate the TTD in global health status/QoL, physical functioning, role functioning, dyspnea, cough, and chest pain for MK-7684A compared to pembrolizumab alone in participants with PD-L1 TPS ≥50%, in participants with PD-L1 TPS 1% to 49% and in participants with PD-L1 TPS ≥1%
9. To evaluate the safety and tolerability for MK-7684A compared to pembrolizumab alone

Conditions and MedDRA coding

Stage IV non small-cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has a histologically or cytologically confirmed diagnosis of Stage IV: M1a, M1b, or M1c non-small cell lung cancer (NSCLC) per the American Joint Committee on Cancer (AJCC) Staging Manual, version 8.
2. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as determined by the local site assessment.
3. Has confirmation that epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)-, or reactive oxygen species proto-oncogene 1 (ROS1)-directed therapy is not indicated as primary therapy and absence of ALK and ROS1 gene rearrangements.
4. Has provided tumor tissue that demonstrates Programmed Cell Death 1 Ligand 1 (PD-L1) expression in ≥1% of tumor cells as assessed by immunohistochemistry (IHC) at a central laboratory.
5. Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 assessed within 7 days prior to randomization.
6. Has a life expectancy of at least 3 months.
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) • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention
8. Has adequate organ function.

Exclusion criteria 22

1. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
2. Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC.
3. Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 6 months before the diagnosis of metastatic NSCLC.
4. Participants must have recovered from all AEs due to previous therapies to Grade ≤1 or baseline. Participants with Grade ≤2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
5. Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)
6. Has received previous treatment with another agent targeting the T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) receptor pathway.
7. Has received radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
8. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines is allowed
9. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed in the study as long as they are mRNA vaccines, replication incompetent adenoviral vaccines, or inactivated vaccines. These vaccines will be treated just as any other concomitant therapy.
10. Investigational vaccines (i.e., those not licensed or approved for Emergency Use) are not allowed.
11. 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.
12. Has known active or untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks by repeat imaging, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab/vibostolimab or pembrolizumab and/or any of its excipients.
14. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
15. 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 to the first dose of study intervention.
16. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
17. Has a known history of interstitial lung disease. Lymphangitic spread of the NSCLC is not exclusionary.
18. Has an active infection requiring systemic therapy.
19. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
20. Has a known history of Hepatitis B or known active Hepatitis C virus infection.
21. Has a history or current evidence of any condition, therapy, or laboratory abnormality that prevents the participant from receiving platinum-doublet chemotherapy for first line NSCLC, or that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
22. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50%

Secondary endpoints 25

1. OS in Participants With PD-L1 TPS ≥1%
2. OS in Participants With PD-L1 TPS 1% to 49%
3. Progression-Free Survival (PFS) in Participants With PD-L1 TPS ≥1%
4. PFS in Participants With PD-L1 TPS ≥50%
5. Objective Response Rate (ORR) in Participants With PD-L1 TPS ≥1%
6. PFS in Participants With PD-L1 TPS 1% to 49%
7. ORR in Participants With PD-L1 TPS ≥50%
8. ORR in Participants With PD-L1 TPS 1% to 49%
9. Duration of Response (DOR) in Participants With PD-L1 TPS ≥50%
10. DOR in Participants With PD-L1 TPS 1% to 49%
11. DOR in Participants With PD-L1 TPS ≥1%
12. Change from Baseline in Global Health Status/Quality of Life (QoL) (Items 29, 30) Combined Score on the European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30) by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
13. Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
14. Change from Baseline in Role Functioning (Items 6, 7) Combined Score on the EORTC QLQ-C30 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
15. Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
16. Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13) by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
17. Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
18. Time to Deterioration (TTD) in Global Health Status/QoL (Items 29, 30) Combined Score on the EORTC QLQ-C30 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
19. TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
20. TTD in Role Functioning (Items 6, 7) Combined Score on the EORTC QLQ-C30 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
21. TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
22. TTD in Cough Score (Item 31) on the EORTC QLQ-LC13 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
23. TTD in in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 by PD-L1 TPS Subgroup (≥1%, 1%-49%, ≥50%)
24. Number of Participants Who Experienced One or More Adverse Events (AEs)
25. Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)

Investigational products

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

Test 1

Comparator 1

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

Ana Nunes

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Ana Nunes

Third parties 11

Locations

2 EU/EEA countries · 12 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 33 files

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

Application history

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