Clinical trial NCT06731907: A Study of Pembrolizumab With or Without Chemotherapy in Combination With Additional Treatments for Advanced Non-Small Cell Lung Cancer (NSCLC) (MK-3475-01G/KEYMAKER U01)
Official title: KEYMAKER-U01 Substudy 01G: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents in Combination With Pembrolizumab With or Without Platinum-based Chemotherapy in Treatment-Naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Lung Neoplasms
Lung Cancer
Pulmonary Neoplasms
Pulmonary Cancer
Non-Small Cell Lung Carcinoma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2024-12-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multi site, rolling-arm study.
Primary purpose: TREATMENT

Brief summary: Researchers are investigating new treatments for untreated advanced non-small cell lung cancer (NSCLC), which is the most common form of lung cancer and lung cancer that has spread beyond surgical removal. Standard treatments include immunotherapy, such as pembrolizumab, and chemotherapy. This study aims to determine the effectiveness of adding other treatments, including the human epidermal growth factor receptor 3-directed antibody-drug conjugate (HER3-DXd) patritumab deruxtecan, to pembrolizumab, with or without chemotherapy. The primary goals are to assess safety and efficacy of the treatments.


Eligibility criteria: Inclusion Criteria:

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

* Histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) Staging Manual Version 8.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 7 days before randomization.
* Has archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided.
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on ART.
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to treatment randomization.

Exclusion Criteria:

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

* Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
* Participants with squamous histology are excluded if there is a known tumor-activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) or c ros oncogene 1 (ROS1) gene rearrangement.
* Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement.
* Has evidence of any leptomeningeal disease.
* Has known history of, or active, neurologic paraneoplastic syndrome.
* Has clinically significant corneal disease.
* Has myocardial infarction within 6 months.
* Has New York Heart Association (NYHA) Classes 3 or 4 congestive heart failure.
* Has uncontrolled angina pectoris within 6 months.
* Has cardiac arrhythmia requiring ongoing antiarrhythmic treatment.
* Has history of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
* Has bradycardia of less than 50 beats per minute (bpm) unless the participant has a pacemaker.
* Has history of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
* Has coronary/peripheral artery bypass graft within 6 months.
* Has complete left bundle branch block.
* Has inadequate washout period from prior concomitant therapy as specified in protocol before randomization.
* Has received prior treatment with a topoisomerase I inhibitor or an anti-HER3 antibody and/or ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor.
* Has received prior systemic anticancer therapy for their metastatic NSCLC.
* Has received prior therapy with an anti- programmed cell death 1 protein (anti-PD-1), anti- programmed cell death ligand 1 protein (anti-PD-L1), or anti- programmed cell death ligand 2 protein (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
* Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation related toxicity requiring corticosteroids.
* Has received radiation therapy to the lung that is \>30 gray within 6 months of start of study intervention.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has severe hypersensitivity to any of the study interventions and/or any of their excipients.
* Has active autoimmune disease that has required systemic treatment in the past 2 years.
* Has active infection requiring systemic therapy.
* Has concurrent active Hepatitis B and Hepatitis C virus infection.
* Have not adequately recovered from major surgery or have ongoing surgical complications.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to ~ 5 years
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to ~ 5 years
measure: Number of Participants Discontinuing Study Drug Due to AEs
timeFrame: Up to ~ 2 years
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to ~ 5 years
measure: Progression-free Survival (PFS)
timeFrame: Up to ~ 5 years
measure: Overall Survival (OS)
timeFrame: Up to ~ 5 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: MedStar Franklin Square Medical Center ( Site 0033)
state: Maryland
city: Fargo
country: United States
facility: Sanford Fargo Medical Center ( Site 0039)
state: North Dakota
city: Thessaloniki
country: Greece
facility: European Interbalkan Medical Center-Oncology Department ( Site 0205)
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 0076)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 0074)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0077)
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
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152)
state: Zachodniopomorskie
city: Barcelona
country: Spain
facility: HOSPITAL CLÍNIC DE BARCELONA ( Site 0092)
city: Madrid
country: Spain
facility: Hospital Universitario Quiron Madrid ( Site 0091)
city: Cherkasy
country: Ukraine
facility: CNE CC of Oncology Hematol ( Site 0130)
state: Cherkaska Oblast
city: Ivano-Frankivsk
country: Ukraine
facility: CNCE Precarpathian Clinical Oncologic Center ( Site 0131)
state: Ivano-Frankivska Oblast
city: Kyiv
country: Ukraine
facility: VISION PARTNER Medical Centre ( Site 0134)
state: Kyivska Oblast
city: Vinnytsia
country: Ukraine
facility: Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council" ( Site 0133)
state: Vinnytska Oblast
city: Kyiv
country: Ukraine
facility: Shalimov Institute of Surgery and Transplantation ( Site 0135)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: