Open Phase I/II Study in Umbrella Platform Design of Experimental Agents with Pembrolizumab (MK-3475) in Participants with Advanced Esophageal Cancer Who Have Previously Received PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06B
Descrizione riassuntiva dello studio
This study aims to determine whether the combinations of the study drugs being tested are safe and effective for the treatment of esophageal squamous cell carcinoma. The study investigates the safety and efficacy of Pembrolizumab (immunotherapy) with or without chemotherapy in combination with new experimental substances in patients who have already been treated with a PD-1/PD-L1 antibody. Approximately 30 patients per treatment arm are expected to participate worldwide. One of the arms consists solely of chemotherapy. Two additional arms consist of the standard treatment with Pembrolizumab plus a new substance and the combination with chemotherapy or Lenvatinib. New arms may be opened as soon as a new substance from a previous study proves promising.
(BASEC)
Intervento studiato
In tumor control, the immune system plays an important role. Many of the substances used here support the immune system in fighting the tumor. Here are the mechanisms of action of the current investigational agents in this study:
-Pembrolizumab is an antibody that can inhibit immune suppression by the tumor and thus enhance the body's natural fight against it.
-MK-4830 is an antibody with high specificity for binding to the ILT4 receptor. This inhibits its interactions with certain molecules, thereby improving the body's immune response against tumors.
-Lenvatinib is an inhibitor of various molecules that promote cell growth and the formation of new blood vessels in tumor cells. By inhibiting the formation of new blood vessels, the nutrient supply to the tumor is reduced, thereby slowing its growth. Additionally, Lenvatinib has been shown to increase immune system activation within the tumor.
The chemotherapies that may be used in this study are Irinotecan or Paclitaxel. These are standard therapies for patients with this cancer.
After a thorough eligibility assessment and detailed information, the participant is included in the study and randomly assigned to one of the three currently planned treatment arms:
A) Treatment with chemotherapy
B) Treatment with Pembrolizumab, MK-4830, and chemotherapy
C) Treatment with Pembrolizumab, MK-4830, and Lenvatinib
The probability of assignment is equal for all treatment arms, although not all arms will always be open.
This study is an open-label study, meaning that both the physician and the participants know which treatment group they have been assigned to.
The treatment duration is approximately two years, as long as safety is ensured and the medications show efficacy. During and after the treatment phase, health status will be regularly monitored for any potential progression of the cancer condition through imaging studies.
As part of the study visits, various measures and examinations may be performed, including: discussion of health status and current medication, completion of a questionnaire, administration of the study medication (intravenous and/or oral), imaging procedures (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
This study examines patients with advanced esophageal cancer (esophageal squamous cell carcinoma) who have already been treated with a PD-1/PD-L1 antibody and for whom chemotherapy (platinum-based first-line therapy) has not led to an improvement in their cancer condition. Esophageal cancer, also known as esophageal carcinoma, is a cancer that begins in the esophagus. The esophagus is the tube through which food and drinks pass from the mouth to the stomach. An esophageal carcinoma can spread to other parts of the body. There are two common types of esophageal carcinomas: - Esophageal adenocarcinoma: usually starts in the lower part of the esophagus. - Esophageal squamous cell carcinoma: usually starts in the upper and middle parts of the esophagus. This study exclusively examines patients with esophageal squamous cell carcinoma. In Switzerland, approximately 600 people are diagnosed with esophageal cancer each year, with only a minority having the variant of esophageal squamous cell carcinoma. The first-line treatment with a platinum-based combination chemotherapy has not changed over the years. Recently, new findings have shown that a combination of chemotherapy and immunotherapy as first-line treatment can significantly improve treatment efficacy. Despite recent advances in the treatment of esophageal cancer, there remains a significant challenge as many patients become resistant to chemotherapeutics and the disease is often diagnosed only at an advanced stage.
(BASEC)
• Confirmed diagnosis of locally advanced, metastatic, or unresectable esophageal cancer (ESCC "esophageal squamous cell carcinoma") and need for second-line therapy • Documented disease progression after first-line therapy with a platinum agent and prior treatment with a PD-1/PD-L1 antibody (as combination therapy with chemotherapy or monotherapy). • Controlled blood pressure (blood pressure ≤150/90 mmHg), with or without antihypertensive medication, and no change in antihypertensive medications within 1 week prior to randomization (BASEC)
Criteri di esclusione
• Prior treatment with VEGF TKI (including Lenvatinib) or anti-VEGF antibodies; any treatment targeting other stimulatory or co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, or CD137) or a substance targeting ILT4 or HLA-G. • Immunosuppression or chronic systemic steroid therapy or any form of other immunosuppressive therapy within the last 7 days prior to the first dose of the study medication. • Clinically significant cardiovascular disease within 12 months after the first treatment with the study medication (with exceptions) (BASEC)
Luogo dello studio
Chur, Ginevra
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Switzerland Merck Sharp & Dohme LLC, USA
(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)
Informazioni scientifiche
Merck Sharp & Dohme LLC,
1-888-577-8839
klaudia.georgi@cluttermsd.com(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione etica Zurigo
(BASEC)
Data di approvazione del comitato etico
02.05.2023
(BASEC)
ID di studio ICTRP
NCT05319730 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer Previously Exposed to PD-1/PD-L1 Treatment: Substudy 06B (BASEC)
Titolo accademico
A Phase 1/2 Open-Label, Umbrella Platform Design Study of Investigational Agents With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer Previously Exposed to PD-1/PD-L1 Treatment (KEYMAKER-U06): Substudy 06B (ICTRP)
Titolo pubblico
A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B) (ICTRP)
Malattie studiate
Esophageal Squamous Cell Carcinoma (ICTRP)
Intervento studiato
Drug: PaclitaxelDrug: IrinotecanBiological: PembrolizumabBiological: MK-4830Drug: LenvatinibBiological: Sacituzumab tirumotecanDrug: AntihistamineDrug: H2 Receptor AntagonistDrug: Acetaminophen (or equivalent)Drug: Dexamethasone (or equivalent)Drug: Steroid Mouthwash (dexamethasone or equivalent)Drug: Supportive care measures (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Criteri di inclusione/esclusione
The main inclusion and exclusion criteria include but are not limited to the following:
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of metastatic or locally
advanced unresectable esophageal squamous cell carcinoma (ESCC)
- Has experienced investigator documented radiographic or clinical disease progression
on one prior line of standard therapy, that includes a platinum agent and previous
exposure to an anti-programmed cell death 1 (PD1)/programmed cell death ligand 1
(PD-L1) based therapy
- Has an evaluable baseline tumor sample (newly obtained or archival) for analysis
- Has adequately controlled blood pressure (BP) with or without antihypertensive
medications
- Participants who have adverse events (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 or participants who have =Grade 2
neuropathy are eligible
Exclusion Criteria:
- Direct invasion into adjacent organs such as the aorta or trachea
- Has experienced weight loss >10% over approximately 2 months prior to first dose of
study therapy
- 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
- Currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks before the first dose of
study intervention
- 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 medication
- Known additional malignancy that is progressing or has required active treatment
within the past 3 years, except basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, or carcinoma in situ that has undergone potentially curative
therapy
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Active autoimmune disease that has required systemic treatment in past 2 years
- Participants with human immunodeficiency virus (HIV) with a history of Kaposi's
sarcoma and/or Multicentric Castleman's Disease
- Concurrent active hepatitis B and hepatitis C virus infection
- History of allogenic tissue/solid organ transplant
- Clinically significant cardiovascular disease within 12 months from first dose of
study intervention
- Known gastrointestinal (GI) malabsorption or any other condition that may affect the
absorption of lenvatinib. (Not applicable to actively enrolling arms as of Amendment
5)
- Has risk for significant GI bleeding such as a serious nonhealing wound, peptic
ulcer, or bone fracture within 28 days prior to allocation/randomization,
significant bleeding disorders, vasculitis, or has had a significant bleeding
episode from the GI tract within 12 weeks prior to allocation/randomization. (Not
applicable to actively enrolling arms as of Amendment 5) (ICTRP)
non disponibile
Endpoint primari e secondari
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During Safety Lead-in Phase;Number of Participants Experiencing Adverse Events (AEs) During Safety Lead-in Phase;Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase;Objective Response Rate (ORR) (ICTRP)
Progression-Free Survival (PFS);Duration of Response (DOR);Overall Survival (OS);Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase;Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
non disponibile
Contatti aggiuntivi
Medical Director;Toll Free Number, Trialsites@msd.com, 1-888-577-8839, Merck Sharp & Dohme LLC, (ICTRP)
ID secondari
jRCT2031220582, 2023-505189-26-00, U1111-1291-1987, MK-3475-06B, KEYMAKER-U06B, 2021-005443-76, 3475-06B (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT05319730 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile