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)

Overview

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.

Interventions

• Biological Pembrolizumab (neoadjuvant)
  Before surgery neoadjuvant Pembrolizumab 200 mg by intravenous (IV) infusion on day 1 of each 21-day cycle for 4 cycles
• Drug Cisplatin
  Cisplatin 75 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
• 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.
• Drug Pemetrexed
  In nonsquamous tumors Pemetrexed 500 mg/m\^2 by IV infusion on day 1 of each 21-day cycle for 4 cycles
• Drug Sacituzumab tirumotecan
  Sacituzumab tirumotecan 4 mg/kg by IV infusion on day 1 of each 14-day cycle for up to 6 cycles
• Drug H1 receptor antagonist
  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

Primary outcome measures

• Pathological Complete Response (pCR) [Time frame: Up to approximately 20 weeks]
• Percent Residual Viable Tumor (%RVT) [Time frame: Up to approximately 20 weeks]

Secondary outcome measures (11)

• 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

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 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• Southern Cancer Center (SCC) ( Site 8004) — Daphne
• Sansum Clinic (Ridley Tree) ( Site 8012) — Santa Barbara
• Rocky Mountain Cancer Centers (RMCC) ( Site 8011) — Lone Tree
• MedStar Franklin Square Medical Center ( Site 0033) — Baltimore
• Oncology Associates of Oregon, P.C.(Willamette Valley Cancer Institute) (WVCI) ( Site 8006 — Eugene
• Texas Oncology - Central/South Texas ( Site 8009) — Austin
• Texas Oncology - Northeast Texas ( Site 8005) — Tyler
• Virginia Cancer Specialists (VCS) ( Site 8002) — Fairfax

Ukraine · 7 centers

• CNE CC of Oncology Hematol ( Site 0130) — Cherkasy
• Municipal Enterprise "Bukovinian сlinical oncology сenter" ( Site 0139) — Chernivtsi
• CNCE Precarpathian Clinical Oncologic Center ( Site 0131) — Ivano-Frankivsk
• MNPE LTMU Multidisc. Clin. Hosp. of Emerg. and Intens. Care ( Site 0132) — Lviv
• ME RIVNE REGIONAL ANTITUMOR CENTER ( Site 0460) — Rivne
• Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional — Vinnytsia
• Shalimov Institute of Surgery and Transplantation ( Site 0138) — Kyiv

Turkey (Türkiye) · 5 centers

• Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 0702) — Adana
• Hacettepe Universite Hastaneleri-oncology hospital ( Site 0700) — Ankara
• Akdeniz Universitesi Hastanesi-Medical Oncology ( Site 0704) — Antalya
• İzmir Suat Seren Chest Disease Training & Research Hospital ( Site 0701) — Izmir
• Ondokuz Mayıs Universitesi-Oncology department ( Site 0706) — Samsun

Greece · 4 centers

• Alexandra General Hospital of Athens Oncology-Hematology Unit ( Site 0203) — Athens
• ATTIKON GENERAL UNIVERSITY HOSPITAL-Oncology ( Site 0202) — Athens
• Metropolitan Hospital-4th Oncology Dept ( Site 0201) — Athens
• University General Hospital of Heraklion ( Site 0200) — Heraklion

Italy · 4 centers

• Azienda Ospedaliera Universitaria Careggi ( Site 0173) — Florence
• Ospedale San Raffaele. ( Site 0171) — Milan
• Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175) — Milan
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sac — Roma

Chile · 3 centers

• Centro de Estudios Clínicos SAGA ( Site 0162) — Santiago
• FALP ( Site 0161) — Santiago
• Bradfordhill ( Site 0160) — Santiago

Hungary · 3 centers

• Petz Aladar Egyetemi Oktato Korhaz-Pulmonológia (Dr. Szalai Zsuzsanna) ( Site 0062) — Győr
• Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 0061) — Szolnok
• Országos Korányi Pulmonológiai Intézet ( Site 0060) — Budapest

Poland · 3 centers

• Wielkopolskie Centrum Pulmonologii i Torakochirurgii-Oddzial Onkologii Klinicznej z Pododd — Poznan
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Kl — Warsaw
• Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150) — Gdansk

Spain · 1 center

• Hospital Clinic de Barcelona ( Site 0092) — Barcelona

Identifiers

NCT: NCT06788912 · 3475-01E · MK-3475-01E · KEYMAKER-U01 · 2023-509234-19-00 · U1111-1299-6753

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗