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

Merck Sharp & Dohme (MSD)

Status and phase

Enrolling

Phase 2

Conditions

Lung Neoplasm Malignant

Treatments

Drug: Carboplatin

Drug: Gemcitabine

Drug: Pemetrexed

Drug: H2 receptor antagonist

Biological: Pembrolizumab (neoadjuvant)

Drug: Sacituzumab tirumotecan

Biological: Pembrolizumab (adjuvant)

Drug: Cisplatin

Drug: Paclitaxel

Drug: Dexamethasone (or equivalent)

Drug: Acetaminophen (or equivalent)

Drug: Steroid mouthwash (dexamethasone or equivalent)

Drug: Antihistamine

Study type

Interventional

Funder types

Industry

Identifiers

NCT06788912

2023-509234-19 (Registry Identifier)

U1111-1299-6753 (Registry Identifier)

MK-3475-01E (Other Identifier)

KEYMAKER-U01 (Other Identifier)

3475-01E

Details and patient eligibility

About

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.

Enrollment

60 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

60 participants in 2 patient groups

Pembrolizumab + Platinum

Active Comparator group

Description:

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) .

Treatment:

Drug: Paclitaxel

Drug: Cisplatin

Biological: Pembrolizumab (adjuvant)

Biological: Pembrolizumab (neoadjuvant)

Drug: Pemetrexed

Drug: Gemcitabine

Drug: Carboplatin

Pembrolizumab + Sacituzumab tirumotecan

Experimental group

Description:

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.

Treatment:

Drug: Antihistamine

Drug: Steroid mouthwash (dexamethasone or equivalent)

Drug: Acetaminophen (or equivalent)

Drug: Dexamethasone (or equivalent)

Drug: Paclitaxel

Drug: Cisplatin

Biological: Pembrolizumab (adjuvant)

Drug: Sacituzumab tirumotecan

Drug: H2 receptor antagonist

Biological: Pembrolizumab (neoadjuvant)

Drug: Pemetrexed