Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
pembrolizumab/vibostolimab coformulation+chemotherapy+radiotherapy
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 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. As of protocol amendment 4, participants receiving pembrolizumab/vibostolimab must stop ongoing treatment with pembrolizumab/vibostolimab and will be offered the option to transition to post-cCRT durvalumab consolidation therapy, to complete up to 1 year of consolidation immunotherapy.
  • Biological: pembrolizumab/vibostolimab
    Administered as an intravenous (IV) infusion
    Other names:
    • MK-7684A
  • Biological: durvalumab
    Administered as an IV infusion
    Other names:
    • IMFINZI®
  • Drug: cisplatin
    Cisplatin 75 mg/m^2 administered as an IV infusion in combination with pemetrexed on Day 1 of Cycles 1-3 for non-squamous histology only; In combination with etoposide, cisplatin 50 mg/m^2 is administered on Days 1, 8 of Cycles 1-2 and Days 8, 15 of Cycle 3
    Other names:
    • PLATINOL-AQ®
  • Drug: pemetrexed
    Pemetrexed 500 mg/m^2 administered as an IV infusion on Day 1 of Cycles 1-3 for non-squamous histology only
    Other names:
    • ALIMTA®
  • Drug: etoposide
    Etoposide 50 mg/m^2 is administered as an IV infusion on Days 1-5 of Cycles 1-2 and Days 8-12 of Cycle 3;
    Other names:
    • TOPOSAR®
  • Drug: carboplatin
    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, administered as an IV infusion
    Other names:
    • PARAPLATIN®
  • Drug: paclitaxel
    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, administered as an IV infusion
    Other names:
    • TAXOL®
  • Radiation: thoracic radiotherapy
    60 Gray [Gy] in 2 Gy fractions for 30 days total administered as an external beam radiation
Active Comparator
chemotherapy+radiotherapy+durvalumab
For the first 3 cycles, participants will receive investigator's choice of platinum doublet chemotherapy and concurrent standard thoracic radiotherapy 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.
  • Biological: durvalumab
    Administered as an IV infusion
    Other names:
    • IMFINZI®
  • Drug: cisplatin
    Cisplatin 75 mg/m^2 administered as an IV infusion in combination with pemetrexed on Day 1 of Cycles 1-3 for non-squamous histology only; In combination with etoposide, cisplatin 50 mg/m^2 is administered on Days 1, 8 of Cycles 1-2 and Days 8, 15 of Cycle 3
    Other names:
    • PLATINOL-AQ®
  • Drug: pemetrexed
    Pemetrexed 500 mg/m^2 administered as an IV infusion on Day 1 of Cycles 1-3 for non-squamous histology only
    Other names:
    • ALIMTA®
  • Drug: etoposide
    Etoposide 50 mg/m^2 is administered as an IV infusion on Days 1-5 of Cycles 1-2 and Days 8-12 of Cycle 3;
    Other names:
    • TOPOSAR®
  • Drug: carboplatin
    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, administered as an IV infusion
    Other names:
    • PARAPLATIN®
  • Drug: paclitaxel
    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, administered as an IV infusion
    Other names:
    • TAXOL®
  • Radiation: thoracic radiotherapy
    60 Gray [Gy] in 2 Gy fractions for 30 days total administered as an external beam radiation

More Details

Status
Active, not recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Detailed Description

As of protocol amendment 4, participants receiving combination vibostolimab and pembrolizumab (MK-7684A) discontinued treatment due to lack of efficacy observed in other MK-7684A studies, and are given the option to transition to durvalumab therapy.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.