Clinical trial NCT06788912: Pembrolizumab (MK-3475) Plus Investigational Agents in Resectable Non-small Cell Lung Cancer (NSCLC) (MK-3475-01E/KEYMAKER-U01)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lung Neoplasm Malignant
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2025-01-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 criteria: The main inclusion and exclusion criteria include but are not limited to the following:

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.

Primary outcomes:
measure: Pathological Complete Response (pCR)
timeFrame: Up to approximately 20 weeks
measure: Percent Residual Viable Tumor (%RVT)
timeFrame: Up to approximately 20 weeks
Secondary outcomes:
measure: Percentage of Participants Who Report at Least 1 Adverse Event (AE)
timeFrame: Up to approximately 5 years
measure: Percentage of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 1 year
measure: Event-free Survival (EFS)
timeFrame: Up to approximately 5 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: Up to approximately 5 years
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 12 weeks
measure: Percentage of Participants Who Experience a Perioperative Complication
timeFrame: Up to approximately 20 weeks
measure: Mean Length of Hospital Stay
timeFrame: Up to approximately 20 weeks
measure: Percentage of Participants Who Require Hospital Readmission after Discharge
timeFrame: Up to approximately 20 weeks
measure: Mean Length of Surgery
timeFrame: Up to approximately 20 weeks
measure: Percentage of Participants Who Require a Blood Transfusion
timeFrame: Up to approximately 20 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: MedStar Franklin Square Medical Center ( Site 0033)
state: Maryland
city: Santiago.
country: Chile
facility: Centro de Estudios Clínicos SAGA ( Site 0162)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: FALP ( Site 0161)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill ( Site 0160)
state: Region M. De Santiago
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi ( Site 0173)
state: Toscana
city: Milano
country: Italy
facility: Ospedale San Raffaele. ( Site 0171)
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)
state: Pomorskie
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Pulmonologii i Torakochirurgii-Oddzial Onkologii Klinicznej z Pododdzialem Dz ( Site 0153)
state: Wielkopolskie
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: