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)

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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