A Trial of Pembrolizumab in Combination With Chemotherapy and Radiotherapy in Stage III NSCLC (KEYNOTE-799, MK-3475-799)

Browse trials for

• Lung Neoplasms 7,243
• Carcinoma, Non-Small-Cell Lung 6,488

Keywords

• Programmed Cell Death-1 (PD1, PD-1)
• Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
• Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 216 is above the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Study arms

• Experimental
  Cohort A

  Participants received 1 cycle of carboplatin area under the curve (AUC) 6 mg/mL/min with paclitaxel 200 mg/m\^2 and pembrolizumab 200 mg on Day 1. Approximately 3 weeks later, participants received carboplatin AUC 2 mg/mL/min with paclitaxel 45 mg/ m\^2 administered weekly for 6 weeks along with 2 cycles of pembrolizumab 200 mg administered every 3 weeks (Q3W) in conjunction with standard thoracic radiotherapy (TRT) (60 Gray \[Gy\] in 2 Gy fractions administered 5 days per week for 6 weeks). Participants then received 14 additional cycles of pembrolizumab 200 mg administered Q3W. 1 cycle=21 days.

  Drug: Pembrolizumab 200 mg · Drug: Paclitaxel 45 mg/m^2 · Drug: Carboplatin AUC6 · Radiation: Thoracic Radiation Therapy (TRT) · Drug: Paclitaxel 200 mg/m^2 · Drug: Carboplatin AUC2

• Experimental
  Cohort B

  Participants received 3 cycles of cisplatin 75 mg/m\^2 with pemetrexed 500 mg/m\^2 and pembrolizumab 200 mg on Day 1 of each cycle. Treatment was given in conjunction with standard TRT (60 Gy in 2 Gy fractions administered 5 days per week for 6 weeks) in cycles 2 and 3. Participants then received 14 additional cycles of pembrolizumab 200 mg administered Q3W. 1 cycle=21 days.

  Drug: Pembrolizumab 200 mg · Drug: Cisplatin 75 mg/m^2 · Drug: Pemetrexed 500 mg/m^2 · Radiation: Thoracic Radiation Therapy (TRT)

Interventions

• DrugPembrolizumab 200 mg

  Pembrolizumab 200 mg intravenous (IV) infusion on Days 1 of each 3-week cycle for up to 17 cycles

  Also known as: MK-3475

• DrugPaclitaxel 45 mg/m^2

  Paclitaxel 45 mg/m\^2 IV infusion on Days 1, 8, 15 of each 3-week cycle for Cycles 2, and 3 during radiation therapy.

• DrugCarboplatin AUC6

  Carboplatin AUC6 IV infusion on Day 1 of the 21-day cycle for Cycle 1.

• DrugCisplatin 75 mg/m^2

  Cisplatin 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, 3.

• DrugPemetrexed 500 mg/m^2

  Pemetrexed 500 mg/m\^2 IV infusion on Day 1 of each 21-day cycle for Cycles 1, 2, and 3.

• RadiationThoracic Radiation Therapy (TRT)

  The target total dose of TRT will be 60 Gy in 30 daily fractions of 2 Gy, prescribed to the planning target volume.

• DrugPaclitaxel 200 mg/m^2

  Paclitaxel 200 mg/m\^2 IV infusion on Day 1 of the 21-day cycle of Cycle 1.

• DrugCarboplatin AUC2

  Carboplatin AUC2 IV infusion on Day 1, 8, 15 for Cycles 2 and 3 during radiation therapy.

Primary outcomes

1. Percentage of Participants Who Developed Grade 3 or Higher Pneumonitis

   Pneumonitis included the MedDRA preferred terms for radiation pneumonitis are acute interstitial pneumonitis, autoimmune lung disease, interstitial lung disease, pneumonitis, idiopathic pneumonia syndrome, organizing pneumonia, and immune-mediated pneumonitis. As per common terminology criteria for Adverse Events, version 4.0, pneumonitis was graded as follows: Grade (Gr) 1- asymptomatic, clinical or diagnostic observations only; intervention not indicated; Gr 2- symptomatic, medical intervention indicated, limiting instrumental activities of daily living (ADL); Gr 3- severe symptoms; limiting self-care activities of daily living (ADL), oxygen indicated; Gr 4- life-threatening respiratory compromise; urgent intervention indicated (e.g., tracheotomy or intubation); Gr 5- death.

   Time frame: Up to approximately 3 years

2. Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

   ORR was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using modified RECIST 1.1 by blinded independent central review (BICR).

   Time frame: Up to approximately 3 years

Secondary outcomes

1. Progression Free Survival (PFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

   PFS was defined as the time from the first dose of study treatment to the date of the first documentation of disease progression, as determined by BICR per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeters \[mm\]) in the sum of diameter of target lesions, taking as reference the smallest sum, and/or unequivocal progression of existing non-target lesions, and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using the product-limit (Kaplan-Meier) method for censored data.

   Time frame: Up to approximately 5 1/2 years

2. Overall Survival (OS)

   OS is defined as the time from enrollment to death due to any cause. OS was estimated and analyzed using the product-limit (Kaplan-Meier) method for censored data.

   Time frame: Up to approximately 5 1/2 years

3. Number of Participants Who Experienced an Adverse Event (AE)

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE was assessed.

   Time frame: Up to approximately 1 1/2 years

4. Number of Participants Who Discontinued From Study Treatment Due to an AE

   An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.

   Time frame: Up to approximately 1 year

Baseline characteristics

Publications

• Jabbour SK, Lee KH, Frost N, Breder V, Kowalski DM, Pollock T, Levchenko E, Reguart N, Martinez-Marti A, Houghton B, Paoli JB, Safina S, Park K, Komiya T, Sanford A, Boolell V, Liu H, Samkari A, Keller SM, Reck M. Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. JAMA Oncol. 2021 Jun 4;7(9):1-9. doi: 10.1001/jamaoncol.2021.2301. Online ahead of print. PubMed 34086039 ↗

Related links

• Merck Clinical Trials Information ↗

Study documents

• Protocol and statistical analysis plan · Dec 5, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf