Study of Pembrolizumab/Vibostolimab (MK-7684A) in Combination With Concurrent Chemoradiotherapy Followed by Pembrolizumab/Vibostolimab Versus Concurrent Chemoradiotherapy Followed by Durvalumab in Participants With Stage III Non-small Cell Lung Cancer (MK-7684A-006/KEYVIBE-006)

Merck Sharp & Dohme (MSD)

Status and phase

Enrolling

Phase 3

Conditions

Carcinoma, Non-Small-Cell Lung

Treatments

Drug: carboplatin

Drug: etoposide

Biological: durvalumab

Drug: cisplatin

Radiation: thoracic radiotherapy

Drug: paclitaxel

Drug: pemetrexed

Biological: pembrolizumab/vibostolimab

Study type

Interventional

Funder types

Industry

Identifiers

NCT05298423

PHRR230831-006071 (Registry Identifier)

jRCT2021220015 (Registry Identifier)

2021-005135-23 (EudraCT Number)

7684A-006

KEYVIBE-006 (Other Identifier)

MK-7684A-006 (Other Identifier)

Details and patient eligibility

About

Researchers are looking for new ways to treat people with locally advanced non-small cell lung cancer (NSCLC). The goal of this study is to learn if people who receive the combination of vibostolimab and pembrolizumab (MK-7684A) live longer without the cancer getting worse and live longer overall than people who receive durvalumab.

Enrollment

784 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria

Has pathologically (histologically or cytologically) confirmed diagnosis of NSCLC.
Has Stage IIIA, IIIB, or IIIC NSCLC by American Joint Committee on Cancer Version 8
Is determined to have unresectable, Stage III NSCLC as documented by a multidisciplinary tumor board or by the treating physician in consultation with a thoracic surgeon
Has no evidence of metastatic disease, indicating Stage IV NSCLC, in whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET) or FDG-PET/ computed tomography (CT) and CT or magnetic resonance imaging (MRI) scans of diagnostic quality of chest, abdomen, pelvis and brain
Has measurable disease as defined by RECIST 1.1, with at least 1 lesion being appropriate for selection as a target lesion, as determined by local site investigator/radiology review
Has not received prior treatment (chemotherapy, targeted therapy, or radiotherapy) for their Stage III NSCLC
Has provided tumor tissue sample (tissue biopsy [core, incisional, or excisional])
Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 assessed within 7 days prior to the first administration of study intervention
Has a life expectancy of at least 6 months

Exclusion Criteria

Has small cell lung cancer (SCLC) or tumors with the presence of small cell elements. Mixed squamous/nonsquamous tumors are eligible
Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer
Has received major surgery (with the exception of replacement of vascular access) within 4 weeks before randomization. If the participant had a major operation, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention
Is expected to require any other form of antineoplastic therapy, while on study
Has received colony-stimulating factors (e.g., Granulocyte Colony-Stimulating Factor [G-CSF], Granulocyte Macrophage Colony-Stimulating Factor [GM-CSF], or recombinant erythropoietin) within 28 days prior to the first dose of study intervention
Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
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 medication
Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection
Has a known history of Hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV ribonucleic acid [RNA] qualitative is detected) infection
Has had an allogenic tissue/solid organ transplant

Pemetrexed-specific Criteria:

Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed
Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

784 participants in 2 patient groups

pembrolizumab/vibostolimab coformulation+chemotherapy+radiotherapy

Experimental group

Description:

For the first 3 cycles, participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) intravenously (IV) on Day 1 plus 3 cycles of investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy (60 Gray \[Gy\] in 2 Gy fractions for 30 days total) during Cycles 2, 3. Participants receive pembrolizumab/vibostolimab for Cycles 4-20 or until discontinuation (up to \~14 months). Cycles 1-20 are 21-day cycles. Investigator's choice of chemotherapy: cisplatin 75 mg/m\^2 and pemetrexed 500 mg/m\^2 on Day 1 of Cycles 1-3 for non-squamous histology only; cisplatin 50 mg/m\^2 on Days 1, 8 of Cycles 1-2 and Days 8, 15 of Cycle 3 and etoposide 50 mg/m\^2 on Days 1-5 of Cycles 1-2 and Days 8-12 of Cycle 3; carboplatin area under the curve (AUC) 6 mg/ml/min on Day 1 of Cycle 1 and AUC 2 mg/ml/min on Days 1, 8, 15 of Cycles 2-3 and paclitaxel 200 mg/m\^2 on Day 1 of Cycle 1 and 45 mg/m\^2 on Days 1, 8, 15 of Cycles 2-3.

Treatment:

Biological: pembrolizumab/vibostolimab

Drug: pemetrexed

Drug: paclitaxel

Radiation: thoracic radiotherapy

Drug: cisplatin

Drug: etoposide

Drug: carboplatin

chemotherapy+radiotherapy+durvalumab

Active Comparator group

Description:

For the first 3 cycles, participants will receive investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy (60 Gy in 2 Gy fractions for 30 days total) during Cycles 2 and 3. Following concurrent chemoradiotherapy (cCRT), participants receive durvalumab 10 mg/kg every 2 weeks for up to an additional 26 cycles or until discontinuation (up to approximately 14 months). cCRT Cycles 1-3=21-day cycles; durvalumab Cycles 1-26=14-day cycles. Investigator's choice of chemotherapy: cisplatin 75 mg/m\^2 and pemetrexed 500 mg/m\^2 on Day 1 of Cycles 1-3 for non-squamous histology only; cisplatin 50 mg/m\^2 on Days 1, 8 of Cycles 1-2 and Days 8, 15 of Cycle 3 and etoposide 50 mg/m\^2 on Days 1-5 of Cycles 1-2 and Days 8-12 of Cycle 3; carboplatin area under the curve (AUC) 6 mg/ml/min on Day 1 of Cycle 1 and AUC 2 mg/ml/min on Days 1, 8, 15 of Cycles 2-3 and paclitaxel 200 mg/m\^2 on Day 1 of Cycle 1 and 45 mg/m\^2 on Days 1, 8, 15 of Cycles 2-3.

Treatment:

Drug: pemetrexed

Drug: paclitaxel

Radiation: thoracic radiotherapy

Drug: cisplatin

Biological: durvalumab

Drug: etoposide

Drug: carboplatin