Partial Study 06D: Clinical Study Comparing MK-2870 Administered with Chemotherapy to Standard Chemotherapy in Patients with Advanced Gastroesophageal Adenocarcinoma
Descrizione riassuntiva dello studio
This study examines participants with advanced or metastatic gastroesophageal adenocarcinoma who have already received first-line therapy. The study aims to evaluate the safety and tolerability of MK-2870 plus chemotherapy (Paclitaxel). The safety and efficacy of MK-2870 in combination with Paclitaxel will be investigated compared to standard therapy (antibody therapy/chemotherapy). The standard therapy used in this study is Ramucirumab and Paclitaxel. These are standard treatments for patients with this type of cancer. MK-2870 is an experimental drug consisting of a monoclonal antibody combined 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 known as trophoblast antigen 2 (TROP2). Through this binding, the toxin (KL610023) can specifically attack and damage cancer cells. MK-2870 is being studied in numerous trials for the treatment of various diseases, including tumors in the stomach, at the junction between the stomach and esophagus, or in the esophagus itself. This study is expected to enroll approximately 90 participants worldwide. In Switzerland, about 12 patients will participate in this study. The total study duration is approximately 3 years.
(BASEC)
Intervento studiato
After detailed information, a thorough eligibility assessment, and a collection of medical history, participants will be enrolled in the study.
The study consists of 2 parts. In the first part of the study, different doses of MK-2870 will be tested to determine a recommended dose of MK-2870 in combination with Paclitaxel. Participants who take part in the first part of the study will receive MK-2870 with Paclitaxel.
After the completion of the first part, the second part of the study begins. In the second part of the study, participants will be randomly assigned to one of the two currently planned treatment arms.
• Group 1: Ramucirumab and Paclitaxel (standard therapy)
• Group 2: MK-2870 and Paclitaxel
o In Group 2, the dose of MK-2870 determined and deemed appropriate in Part 1 will be used with Paclitaxel.
New arms may be opened continuously as soon as a new substance from a previous study proves promising. MK-2870, Paclitaxel, and Ramucirumab will be administered via a needle into a vein. This is referred to as intravenous (IV) infusion. MK-2870 will be administered in 6-week cycles. Paclitaxel and Ramucirumab will be administered in 4-week cycles. The treatment duration is approximately two years, as long as safety is ensured and the medications are tolerated. During and after the treatment phase, health status will be regularly monitored for any potential progression of the cancer disease using imaging studies.
This study is an open-label study, meaning that both the investigator and the participants know which treatment group they have been assigned to.
As part of the study visits, various measures and examinations may be performed. These include, among others: discussion of health status and current medication, answering a questionnaire, administration of study medication, imaging procedures (bone scan, CT and/or MRI scans), cardiac examinations (multiple gated acquisition scan (MUGA) or echocardiogram (ECHO) as well as electrocardiogram (12-lead ECG)), collection of blood and urine samples, or tissue (biopsy), as well as examination of vital signs (pulse, blood pressure, etc.).
(BASEC)
Malattie studiate
Gastroesophageal carcinomas are tumors that arise in the stomach, at the junction between the stomach and esophagus (gastroesophageal junction), or in the esophagus itself. The esophagus is the tube that carries food and drink from the mouth to the stomach. Sometimes a gastroesophageal carcinoma can also spread to other parts of the body, which is referred to as metastasis. Adenocarcinoma is the most common type of gastroesophageal carcinoma. It arises from the glandular cells that line the mucosa of the esophagus and stomach. Each year, around 1,000 people in Switzerland are diagnosed with stomach cancer and about 610 people with esophageal cancer. The current standard treatment for advanced/metastatic gastroesophageal adenocarcinomas consists of a combination of chemotherapy and/or immunotherapy. Despite these advances, there are still significant challenges in treatment, as many patients become resistant to chemotherapeutics and the disease is often diagnosed at an advanced stage, with a median survival in the advanced stage of just under 12 months.
(BASEC)
1. Histologically and/or cytologically confirmed diagnosis of a previously treated locally advanced, unresectable, or metastatic adenocarcinoma of the stomach, gastroesophageal junction, or esophagus. 2. Documented disease progression during or after first-line therapy with a platinum/fluoropyrimidine agent in combination with or without immunotherapy. 3. Gastroesophageal adenocarcinoma must not be HER2/neu-positive. (BASEC)
Criteri di esclusione
1. Weight loss of more than 20% over the 3 months prior to the first dose of the study intervention. 2. Immunosuppression or chronic systemic steroid therapy or any form of other immunosuppressive therapy within the last 7 days prior to the first study treatment dose. 3. Previously received treatment with a TROP2-directed antibody-drug conjugate (ADC) and/or chemotherapy based on a topoisomerase-1 inhibitor. (BASEC)
Luogo dello studio
Chur, Ginevra
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Switzerland
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Klaudia Georgi
+41 58 618 33 88
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG
(BASEC)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione etica Zurigo
(BASEC)
Data di approvazione del comitato etico
20.08.2024
(BASEC)
ID di studio ICTRP
NCT06445972 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A Phase 1/2 Open-Label, Umbrella Platform Design Study to Evaluate the Safety and Efficacy of Investigational Agents in Combination With Standard of Care Treatments as the Second-Line Treatment of Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma: Substudy 06D (BASEC)
Titolo accademico
A Phase 1/2 Open-Label, Umbrella Platform Design Study to Evaluate the Safety and Efficacy of Investigational Agents in Combination With Standard of Care Treatments as the Second-Line Treatment of Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma: Substudy 06D (ICTRP)
Titolo pubblico
Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06) (ICTRP)
Malattie studiate
Gastroesophageal JunctionGastroesophageal AdenocarcinomaEsophageal NeoplasmsEsophageal Cancer (ICTRP)
Intervento studiato
Biological: RamucirumabDrug: PaclitaxelBiological: Sacituzumab TirumotecanDrug: Rescue MedicationsBiological: HER3-DXd (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor). (ICTRP)
Criteri di inclusione/esclusione
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
- Has histologically and/or cytologically confirmed diagnosis of previously treated,
second line (2L) (received first line (1L) treatment) gastric adenocarcinoma,
gastroesophageal junction adenocarcinoma, or esophageal adenocarcinoma
- Has metastatic disease or locally advanced, unresectable disease
- Has experienced documented objective radiographic or clinical disease progression
during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or
without immunotherapy
- Tumor tissue must be confirmed as negative for HER2 expression (IHC 0/1+ or IHC2+/in
situ hybridization negative) as classified by American Society of Clinical
Oncology/College of American Pathologists (ASCO-CAP) guidelines
- Can provide a core/excisional biopsy of a tumor lesion not previously irradiated
(collected from a biopsy performed after the most recent systemic anticancer therapy
regimen)
- AEs due to previous anticancer therapies must be =Grade 1 or baseline (except
alopecia and vitiligo). Endocrine-related AEs adequately treated with hormone
replacement are acceptable
- Has Eastern Cooperative Oncology Group performance status of 0 or 1
- Has a life expectancy of at least 3 months
- 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 allocation/randomization
- Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV
viral load is undetectable at screening
- Human Immunodeficiency Virus (HIV)-infected participants must have well controlled
HIV on antiretroviral therapy
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
- Has squamous cell or undifferentiated gastroesophageal cancer
- Has experienced weight loss >20% over 3 months before the first dose of study
intervention
- 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 Grade =2 peripheral neuropathy
- Has active inflammatory bowel disease requiring immunosuppressive medication or
previous history of inflammatory bowel disease
- Has a serious or nonhealing wound or peptic ulcer or bone fracture within 28 days
prior to allocation/randomization
- Has a bowel obstruction, history or presence of inflammatory enteropathy or
extensive intestinal resection (hemicolectomy or extensive small intestine resection
with chronic diarrhea)
- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
- Has experienced any arterial thrombotic event, including myocardial infarction,
unstable angina, cerebrovascular accident, or transient ischemic attack, within 6
months prior to allocation/randomization
- Has uncontrolled arterial hypertension =150/=90 mm mercury (Hg)
- Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or
diuretic drugs within 2 weeks prior to enrollment
- Has undergone major surgery within 28 days prior to allocation/randomization, or
central venous access device placement within 7 days prior to
allocation/randomization or planned major surgery following initiation of study
treatment
- Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin
or similar agents
- Is receiving chronic therapy with nonsteroidal anti-inflammatory agents or other
antiplatelet agents
- Has a history of deep vein thrombosis, pulmonary embolism, or any other significant
thromboembolism during the 3 months prior to allocation/randomization
- Has significant bleeding disorders, vasculitis, or had a significant bleeding
episode from the gastrointestinal (GI) tract within 3 months prior to study entry
- Has history of GI perforation and/or fistulae within 6 months prior to
allocation/randomization
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
Castleman's Disease
- Has received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)- or
HER3-targeted agent, topoisomerase 1 inhibitor-based ADC and/or a topoisomerase 1
inhibitor-based chemotherapy, or any previous systemic therapy targeting vascular
endothelial growth factor (VEGF) or the vascular endothelial growth factor receptor
(VEGFR) signaling pathways
- Has received prior systemic anticancer therapy within 4 weeks before the first dose
of study intervention
- Has received prior radiotherapy within 2 weeks of start of study intervention, or
has 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 known additional malignancy that is progressing or has required active treatment
within the past 3 years. Basal cell carcinoma of the skin, squamous cell carcinoma
of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that
have undergone potentially curative therapy are not excluded
- Has known active central nervous system metastases and/or carcinomatous meningitis
- Has an active infection requiring systemic therapy
- Has concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV
deoxyribonucleic acid) and Hepatitis C virus (defined as anti-HCV antibody positive
and detectable HCV ribonucleic acid) infection
- History of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease, or where suspected
ILD or pneumonitis cannot be ruled out by imaging at screening
- Has severe hypersensitivity (Grade =3) to MK-2870, or HER3-DXd, any of their
excipients, and/or to another biologic therapy
- Has not adequately recovered from major surgery or have ongoing surgical
complications (ICTRP)
non disponibile
Endpoint primari e secondari
Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) During the Safety Lead-In Phase;Percentage of Particiapants who Experience an Adverse Event (AE) During the Safety Lead-In Phase;Percentage of Participants who Discontinue Study Intervention Due to an AE During the Safety Lead-In Phase;Objective Response Rate (ORR) (ICTRP)
Progression Free Survival (PFS);Duration of Response (DOR);Overall Survival (OS);Percentage of Particiapants who Experience an AE During the Efficacy Phase;Percentage of Participants who Discontinue Study Intervention Due to an AE During the Efficacy Phase;Incidence of sacituzumab tirumotecan anti-drug antibody (ADA);Incidence of HER3-DXd ADA (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
Daiichi Sankyo (ICTRP)
Contatti aggiuntivi
Medical Director;Toll Free Number, Trialsites@msd.com, 1-888-577-8839, Merck Sharp & Dohme LLC, (ICTRP)
ID secondari
2023-509306-29-00, U1111-1299-8160, MK-3475-06D, 3475-06D (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT06445972 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile