Pembrolizumab (MK-3475) Plus Investigational Agents in Resectable Non-small Cell Lung Cancer (NSCLC) (MK-3475-01E/KEYMAKER-U01)
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)
Merck Sharp & Dohme LLC
60 participants
Mar 20, 2025
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria5
- Has previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC)
- Able to undergo protocol therapy, including necessary surgery
- Confirmation that epidermal growth factor receptor (EGFR) -directed therapy is not indicated as primary therapy
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 10 days before initiation of study intervention.
- Is able to provide archival or newly obtained core/excisional biopsy of the primary lung tumor or lymph node metastasis.
Exclusion Criteria16
- Has one of the following tumor locations/types: NSCLC involving the superior sulcus, large-cell neuro-endocrine cancer, mixed tumors containing small cell and non-small cell elements, or sarcomatoid tumor.
- Has Grade ≥2 peripheral neuropathy.
- Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
- Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease.
- Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- Received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids.
- 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 intervention.
- Known additional malignancy that is progressing or has required active treatment within the past 5 years.
- Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid) is allowed.
- History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Active infection requiring systemic therapy.
- Hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or Hepatitis C virus (defined as detectable hepatitis C virus (HCV) ribonucleic acid (RNA) \[qualitative\]) infection.
- Known history of human immunodeficiency virus (HIV) infection.
- History of allogeneic tissue/solid organ transplant.
Interventions
Before surgery neoadjuvant Pembrolizumab 200 mg by intravenous (IV) infusion on day 1 of each 21-day cycle for 4 cycles
Cisplatin 75 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
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.
In nonsquamous tumors Pemetrexed 500 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
Sacituzumab tirumotecan 4 mg/kg by IV infusion on day 1 of each 14-day cycle for up to 6 cycles
Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label
Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label
Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label
Administered as rescue medication 8 -10 mg before Sacituzumab tirumotecan infusion per approved product label
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
After surgery adjuvant Pembrolizumab 200 mg by IV infusion on day 1 of each 21-day cycle for 13 cycles
Paclitaxel 175 or 200 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles.
Administered orally as rescue medication 2-5 mL 4 times daily
Locations(31)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06788912