Pembrolizumab (MK-3475) Plus Investigational Agents in Resectable Non-small Cell Lung Cancer (NSCLC) (MK-3475-01E/KEYMAKER-U01)

Purpose

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.

Condition

  • Lung Neoplasm Malignant

Eligibility

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

Inclusion Criteria

  • 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 Criteria

  • 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 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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Pembrolizumab + Platinum 		Neoadjuvant: Prior to surgery pembrolizumab 200 mg every three weeks (Q3W) for 4 cycles (each cycle is 21 days); Cisplatin 75 mg/m^2 Q3W with gemcitabine 1000 mg/m^2 on Day 1 (D1) and Dy 8 (D8) Q3W (squamous tumors), pemetrexed 500 mg/m^2 Q3W (nonsquamous tumors), or paclitaxel 175 mg/m^2 or 200 mg/m^2 q3w (any histology) OR Carboplatin AUC 5 mg/mL• min or AUC 6 mg/mL• min with paclitaxel 175 mg/m^2 or 200 mg/m^2 Q3W (any histology), pemetrexed 500 mg/m^2 Q3W (nonsquamous tumors), or gemcitabine 1000 mg/m^2 on D1 and D8 Q3W (squamous tumors); followed by surgery. Adjuvant: After surgery pembrolizumab 200 mg Q3W for 13 cycles (each cycle is 21 days) .
  • Biological: Pembrolizumab (neoadjuvant)
    Before surgery neoadjuvant Pembrolizumab 200 mg by intravenous (IV) infusion on day 1 of each 21-day cycle for 4 cycles
    Other names:
    • KEYTRUDA®
    • MK-3475
  • Drug: Cisplatin
    Cisplatin 75 mg/m^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
    Other names:
    • PLATINOL®
  • Drug: Gemcitabine
    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.
    Other names:
    • GEMZAR®
  • Drug: Pemetrexed
    In nonsquamous tumors Pemetrexed 500 mg/m^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
    Other names:
    • Alimta®
  • Drug: Carboplatin
    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
    Other names:
    • PARAPLATIN®
  • Biological: Pembrolizumab (adjuvant)
    After surgery adjuvant Pembrolizumab 200 mg by IV infusion on day 1 of each 21-day cycle for 13 cycles
    Other names:
    • KEYTRUDA®
    • MK-3475
  • Drug: Paclitaxel
    Paclitaxel 175 or 200 mg/m^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles.
Experimental
Pembrolizumab + Sacituzumab tirumotecan 		Neoadjuvant: Prior to surgery pembrolizumab 200 mg Q3W for 4 cycles (each cycle is 21 days); sacituzumab tirumotecan 4 mg/kg Q2W for 6 cycles (each cycle is 14 days), followed by surgery. Adjuvant: After surgery pembrolizumab 200 mg Q3W for 13 cycles (each cycle is 21 days). Optional adjuvant platinum-based doublet chemotherapy up to 4 cycles may be given at the investigator's discretion.
  • Biological: Pembrolizumab (neoadjuvant)
    Before surgery neoadjuvant Pembrolizumab 200 mg by intravenous (IV) infusion on day 1 of each 21-day cycle for 4 cycles
    Other names:
    • KEYTRUDA®
    • MK-3475
  • Drug: Cisplatin
    Cisplatin 75 mg/m^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
    Other names:
    • PLATINOL®
  • Drug: Gemcitabine
    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.
    Other names:
    • GEMZAR®
  • Drug: Pemetrexed
    In nonsquamous tumors Pemetrexed 500 mg/m^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
    Other names:
    • Alimta®
  • Drug: Sacituzumab tirumotecan
    Sacituzumab tirumotecan 4 mg/kg by IV infusion on day 1 of each 14-day cycle for up to 6 cycles
    Other names:
    • MK-2870
    • SKB264
  • Drug: Antihistamine
    Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label
  • Drug: H2 receptor antagonist
    Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label
  • Drug: Acetaminophen (or equivalent)
    Administered as rescue medication before Sacituzumab tirumotecan infusion per approved product label
  • Drug: Dexamethasone (or equivalent)
    Administered as rescue medication 8 -10 mg before Sacituzumab tirumotecan infusion per approved product label
  • Drug: Carboplatin
    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
    Other names:
    • PARAPLATIN®
  • Biological: Pembrolizumab (adjuvant)
    After surgery adjuvant Pembrolizumab 200 mg by IV infusion on day 1 of each 21-day cycle for 13 cycles
    Other names:
    • KEYTRUDA®
    • MK-3475
  • Drug: Paclitaxel
    Paclitaxel 175 or 200 mg/m^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles.
  • Drug: Steroid mouthwash (dexamethasone or equivalent)
    Administered orally as rescue medication 2-5 mL 4 times daily

Recruiting Locations

MedStar Franklin Square Medical Center ( Site 0033)
Baltimore, Maryland 21237
Contact:
Study Coordinator
888-577-8839

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com