Clinical study of MK-2870 with Pembrolizumab compared to Pembrolizumab alone in adults who have undergone surgery for non-small cell lung cancer (NSCLC)
Zusammenfassung der Studie
This study evaluates the benefit of adding MK-2870 to Pembrolizumab for patients with operable NSCLC stages II-IIIB(N2). If not all tumor cells are killed after treatment with Pembrolizumab and chemotherapy, patients are included in the second part of the study that takes place after surgery. MK-2870 is an experimental drug consisting of a monoclonal antibody in combination with a toxin (KL610023). Antibodies are proteins produced by the immune system that help the body fight foreign substances such as bacteria or viruses, but also tumors. Monoclonal antibodies bind to specific targets on cells. MK-2870 binds to a target on certain cancer cells called trophoblast antigen 2 (TROP2). Through this binding, the toxin (KL610023) can damage these cancer cells. Pembrolizumab (MK-3475) is an antibody that can prevent the tumor from deceiving the immune system and thus enhance the body's natural fight against the tumor. MK-2870 is being tested in various studies for the treatment of different diseases, including endometrial carcinoma (uterine cancer) and breast cancer. In the study described here, approximately 780 patients are expected to participate worldwide. In Switzerland, about 20 patients will participate in this study. The total duration of the study is approximately 10 years.
(BASEC)
Untersuchte Intervention
After thorough counseling, eligibility assessment, and medical history collection, the patient is included in the study. During the first phase, each patient receives treatment with Pembrolizumab (MK-3475) in combination with tumor-dependent chemotherapy. The treatment occurs every 3 weeks and can last up to 12 weeks. In the next step, patients undergo surgical operation.
After a postoperative recovery period of 4-6 weeks, the second screening phase takes place. Only patients for whom not all tumor cells were killed by the treatment before surgery are included in the second part of the study and are randomly assigned (1:1 ratio) to one of the two treatment groups.
Group 1: Patients receive MK-2870 and Pembrolizumab (MK-3475)
Group 2: Patients receive only Pembrolizumab (MK-3475)
Pembrolizumab (MK-3475) and MK-2870 are administered through a needle in the arm. This is referred to as intravenous (i.v.) infusion. In the 12-week phase before surgery, Pembrolizumab is administered before each chemotherapy every 3 weeks. In the phase after surgery, MK-2870 is administered a total of 20 times every 2 weeks and Pembrolizumab a total of 7 times every 6 weeks. Thus, the duration of the second phase is approximately 42 weeks.
This study is referred to as a "open-label" study. This means that both the participants and the study physician and sponsor know which group the patients have been assigned to in the phase after surgery and thus whether they receive only Pembrolizumab (MK-3475) or MK-2870 with Pembrolizumab.
As part of study appointments, various measures and examinations may be performed, such as: electrocardiogram (ECG), blood and urine tests, tumor biopsy collection, chest and abdomen X-rays (CT and MRI), assessment of general health status, and discussions with medical staff. The study team may also contact participants between visits and after the completion of the study drug intake to inquire about their health status.
(BASEC)
Untersuchte Krankheit(en)
Lung cancer is one of the most common malignant cancers, occurring in about 2.2 million people worldwide in 2020. In Switzerland, lung cancer is the third most common cancer type. There are two main types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The non-small cell lung cancer (NSCLC) studied in this study accounts for about 85% of all lung cancer cases. Depending on the affected tissue, NSCLC is further classified into squamous or non-squamous lung cancer. The main cause of lung cancer is tobacco smoking. Additionally, passive smoking, air pollution, occupational exposure to carcinogenic substances such as asbestos, and genetic predisposition can also increase the risk of lung cancer. The symptoms of lung cancer can vary, but some common signs include persistent cough, shortness of breath, chest pain, weight loss, and fatigue. The diagnosis of lung cancer is made based on various examinations such as chest X-rays and computed tomography (CT). At the time of diagnosis, 18% of patients show disease at early stage I, 22% at stages II and III, and more than half of the patients show advanced disease up to stage IV. The treatment of lung cancer depends on the stage of the disease and other individual factors. Common treatment methods include surgery, radiation therapy, chemotherapy, targeted therapies, and immunotherapies. Early-stage lung cancer can be treated with surgical removal, although in some stages of the disease immunotherapies and targeted therapies may also be applied. Nevertheless, the occurrence of micrometastases often leads to recurrence. This results in both physical and psychological burdens for the patient. More effective early treatments are needed to minimize or prevent the high rates of recurrence. This study targets patients with operable non-small cell lung cancer (NSCLC) at stage II to IIIB (N2).
(BASEC)
1. Confirmed squamous or non-squamous non-small cell lung cancer that can be surgically removed (stage II-IIIB(N2)). 2. Patients must be able to receive Pembrolizumab and chemotherapy as treatment and undergo surgery. 3. After treatment before surgery, residual tumor cells are detected. (BASEC)
Ausschlusskriterien
1. If patients have received certain cancer therapies prior to the start of the study. 2. Presence of specific medical issues regarding the nervous system. 3. Immune system disorders such as autoimmune diseases or immunodeficiency. (BASEC)
Studienstandort
Chur, Freiburg, Lausanne, Andere
(BASEC)
Frauenfeld/Münsterlingen
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Luzern
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Klaudia Georgi
+41 79 512 34 39
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG, Luzern
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
30.04.2024
(BASEC)
ICTRP Studien-ID
NCT06312137 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
MK-2870-019: A Phase 3 Randomized Open-Label Study of Adjuvant Pembrolizumab With or Without MK-2870 in Participants With Resectable Stage II to IIIB (N2) NSCLC not Achieving pCR After Receiving Neoadjuvant Pembrolizumab With Platinum-based Doublet Chemotherapy Followed by Surgery (BASEC)
Wissenschaftlicher Titel
A Phase 3 Randomized Open-Label Study of Adjuvant Pembrolizumab With or Without MK-2870 in Participants With Resectable Stage II to IIIB (N2) NSCLC Not Achieving pCR After Receiving Neoadjuvant Pembrolizumab With Platinum-based Doublet Chemotherapy Followed by Surgery (ICTRP)
Öffentlicher Titel
A Study to Assess Efficacy and Safety of Pembrolizumab With or Without Sacituzumab Tirumotecan (MK- 2870) in Adult Participants With Resectable Non Small Cell Lung Cancer (NSCLC) Not Achieving Pathological Complete Response (pCR) (MK-2870-019) (ICTRP)
Untersuchte Krankheit(en)
Non Small Cell Lung Cancer (ICTRP)
Untersuchte Intervention
Biological: Sacituzumab tirumotecanBiological: PembrolizumabDrug: CisplatinDrug: PemetrexedDrug: GemcitabineDrug: CarboplatinDrug: PaclitaxelDrug: Rescue medication (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
The key inclusion and exclusion criteria include but are not limited to the following:
Inclusion Criteria:
- Has histological or cytological confirmation of squamous or nonsquamous non-small
cell lung cancer (NSCLC), resectable clinical Stage II, IIIA or IIIB (with nodal
involvement [N2]) per AJCC eighth edition guidelines
- Has confirmation that either epidermal growth factor receptor (EGFR)-directed or
anaplastic lymphoma kinase (ALK)-directed therapy is not indicated as primary
therapy
- Is able to undergo surgery based on opinion of investigator after consultation with
surgeon
- Is able to receive neoadjuvant pembrolizumab and platinum-based doublet chemotherapy
- Applies to screening for the adjuvant period only, before randomization: Has not
achieved pathological complete response (pCR) at surgery by local review of
pathology.
- Applies to screening for the adjuvant period only, before randomization: Tumor
tissue sample from surgical resection has been provided for determination of
programmed cell death ligand 1 (PD-L1) and trophoblast cell surface antigen 2
(TROP2) status by central vendor before randomization into the adjuvant period
- Applies to screening for the adjuvant period only, before randomization: Confirmed
to be disease-free based on re-baseline radiological assessment as documented by
contrast enhanced chest/abdomen/pelvis computed tomography (CT) (or magnetic
resonance imaging (MRI)) within 28 days before randomization
- Participants who have AEs due to previous anticancer therapies must have recovered
to =Grade 1 or baseline. Participants with endocrine-related AEs who are adequately
treated with hormone replacement are eligible
- Human immunodeficiency virus (HIV)-infected participants must have well controlled
HIV on antiretroviral therapy (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 at screening
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
viral load is undetectable at least 4 weeks before the start of study intervention
Exclusion Criteria:
- Has one of the following tumor locations/types:
- NSCLC involving the superior sulcus
- Large cell neuro-endocrine cancer (LCNEC)
- Sarcomatoid tumor
- Diagnosis of SCLC or, for mixed tumors, presence of small cell elements
- 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
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease,
including New York Heart Association Class III or IV congestive heart failure,
unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia,
prolongation of QT corrected for heart rate by Fridericia's cube root formula (QTcF)
interval to >480 ms, and/or other serious cardiovascular and cerebrovascular
diseases within the 6 months preceding study intervention
- Has received prior neoadjuvant therapy for their current NSCLC diagnosis
- Has received prior systemic anticancer therapy including investigational agents
within 4 weeks before the first dose of study intervention
- Has received prior radiotherapy within 2 weeks of start of study intervention, or
radiation-related toxicities, requiring corticosteroids
- Has received a live or live-attenuated vaccine within 30 days before the first dose
of study intervention. Administration of killed vaccines is allowed
- Has received an investigational agent or has used an investigational device within 4
weeks prior to study intervention administration
- Has a 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 the first dose of study medication
- Has a known additional malignancy that is progressing or has required active
treatment within the past 5 years
- Has an active autoimmune disease that has required systemic treatment in the past 2
years
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Is an HIV-infected participant with a history of Kaposi's sarcoma and/or
Multicentric Castleman's Disease
- Has a concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV
deoxyribonucleic acid (DNA)) and Hepatitis C virus (defined as anti-HCV antibody
(Ab) positive and detectable HCV ribonucleic acid (RNA)) infection
- Has a history of allogeneic tissue/solid organ transplant
- Has not adequately recovered from major surgery or have ongoing surgical
complications
- Severe hypersensitivity (=Grade 3) to study intervention, any of its excipients,
and/or to another biologic therapy (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Disease-free survival (DFS) as assessed by Blinded Independent Central Review (BICR) (ICTRP)
Overall Survival (OS);Distant metastasis-free survival (DMFS) as assessed by investigator;Disease-Free Survival (DFS) as assessed by investigator;Lung Cancer Specific Survival (LCSS);Number of Participants Who Experience an Adverse Event (AE);Number of Participants Who Discontinue Study Intervention Due to AEs;Change from Baseline in Global Health Status/Quality of Life (QoL) score (Quality of Life Questionnaire (QLQ)-C30 Items 29 and 30);Change from Baseline in Physical Functioning Score (QLQ-C30 Items 1 to 5);Change from Baseline in Role Functioning Score (QLQ-C30 Items 6 and 7);Change from Baseline in Dyspnea scores (QLQ-C30 Item 8);Change from Baseline in Coughing scores (QLQ-LC24 Items 31 and 52);Change from Baseline in Chest pain scores (QLQ-LC24 Item 40) (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Medical Director;Toll Free Number, Trialsites@msd.com, 1-888-577-8839, Merck Sharp & Dohme LLC, (ICTRP)
Sekundäre IDs
2023-508012-35-00, MK-2870-019, jRCT2021240020, U1111-1297-4260, 2870-019 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT06312137 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar