KEYMAKER-U01 Substudy 01E: A Phase 2 Umbrella Study With Rolling Arms of Investigational Agents With or Without Chemotherapy in Combination With Pembrolizumab in Treatment of Participants With Newly Diagnosed Resectable Stages II-IIIB (N2) Non-small Cell Lung Cancer (NSCLC)
Summary
The main goals are after treatment given before surgery, to measure the number of people who have no signs of cancer cells in tumors and lymph nodes removed during surgery; and to learn about whether the cancer gets smaller or goes away by measuring the number of people with a certain number of living cancer cells in the tumor removed during surgery.
Arms & interventions
- BiologicalPembrolizumab (neoadjuvant)
Before surgery neoadjuvant Pembrolizumab 200 mg by intravenous (IV) infusion on day 1 of each 21-day cycle for 4 cycles
- DrugCisplatin
Cisplatin 75 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
- DrugGemcitabine
In squamous tumors Gemcitabine 1000 mg/m\^2 by IV infusion on day 1 and day 8 of each 21-day cycle for 4 cycles.
- DrugPemetrexed
In nonsquamous tumors Pemetrexed 500 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
- DrugSacituzumab tirumotecan
Sacituzumab tirumotecan 4 mg/kg by IV infusion on day 1 of each 14-day cycle for up to 6 cycles
- DrugH1 receptor antagonist
Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label
- DrugH2 receptor antagonist
Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label
- DrugAcetaminophen (or equivalent)
Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label
- DrugDexamethasone (or equivalent)
Administered as rescue medication 8 -10 mg before Sacituzumab tirumotecan infusion per approved product label
- DrugCarboplatin
AUC 5 mg/mL min or AUC 6 mg/mL min by IV infusion on day 1 of each 21-day cycle for 4 cycles
- BiologicalPembrolizumab (adjuvant)
After surgery adjuvant Pembrolizumab 200 mg by IV infusion on day 1 of each 21-day cycle for 13 cycles
- DrugPaclitaxel
Paclitaxel 175 or 200 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles.
- DrugSteroid mouthwash (dexamethasone or equivalent)
Administered orally as rescue medication 2-5 mL 4 times daily
Outcome measures
Primary
Pathological Complete Response (pCR)
pCR is defined as absence of residual viable invasive cancer on hematoxylin- and eosin-stained slides of the resected lung specimen and lymph nodes.
Time frame: Up to approximately 20 weeks
Percent Residual Viable Tumor (%RVT)
%RVT is defined as the percentage of residual tumor estimated by comparing the estimated cross-sectional area of viable tumor with estimated cross-sectional areas of remainder of tumor bed. The tumor bed is defined as the area of tissue occupied by viable tumor or tumoral regression (includes areas of necrosis, foamy macrophages, giant cell reaction, cholesterol cleft granuloma, and inflammation.)
Time frame: Up to approximately 20 weeks
Secondary
Percentage of Participants Who Report at Least 1 Adverse Event (AE)
Time frame: Up to approximately 5 years
Percentage of Participants Who Discontinue Study Treatment Due to an AE
Time frame: Up to approximately 1 year
Event-free Survival (EFS)
Time frame: Up to approximately 5 years
Overall Survival (OS)
Time frame: Up to approximately 5 years
Distant Metastasis-Free Survival (DMFS)
Time frame: Up to approximately 5 years
Objective Response Rate (ORR)
Time frame: Up to approximately 12 weeks
Percentage of Participants Who Experience a Perioperative Complication
Time frame: Up to approximately 20 weeks
Mean Length of Hospital Stay
Time frame: Up to approximately 20 weeks
Percentage of Participants Who Require Hospital Readmission after Discharge
Time frame: Up to approximately 20 weeks
Mean Length of Surgery
Time frame: Up to approximately 20 weeks
Percentage of Participants Who Require a Blood Transfusion
Time frame: Up to approximately 20 weeks
Eligibility criteria
Study locations (8)
Southern Cancer Center (SCC) ( Site 8004)
Daphne, Alabama, 36526
Sansum Clinic (Ridley Tree) ( Site 8012)
Santa Barbara, California, 93105
Rocky Mountain Cancer Centers (RMCC) ( Site 8011)
Lone Tree, Colorado, 80124
MedStar Franklin Square Medical Center ( Site 0033)
Baltimore, Maryland, 21237
Oncology Associates of Oregon, P.C.(Willamette Valley Cancer Institute) (WVCI) ( Site 8006)
Eugene, Oregon, 97401
Texas Oncology - Central/South Texas ( Site 8009)
Austin, Texas, 78705
Texas Oncology - Northeast Texas ( Site 8005)
Tyler, Texas, 75702
Virginia Cancer Specialists (VCS) ( Site 8002)
Fairfax, Virginia, 22031