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JOURNAL ONKOLOGIE – STUDIE

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)

Rekrutierend

NCT-Nummer:
NCT05319730

Studienbeginn:
Mai 2023

Letztes Update:
22.04.2024

Wirkstoff:
Paclitaxel, Irinotecan, Pembrolizumab, MK-4830, Lenvatinib, Antihistamine, H2 Receptor Antagonist, Acetaminophen (or equivalent), Dexamethasone (or equivalent), Sacituzumab tirumotecan

Indikation (Clinical Trials):
Esophageal Neoplasms, Esophageal Squamous Cell Carcinoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 39)

Institut für Klinisch Onkologische Forschung-Klink für Onkologie und Hämatologie ( Site 4801)
60488 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 496976014187» Ansprechpartner anzeigen
Charité Campus Virchow-Klinikum-Klinik Hämatologie Onkologie Tumorimmunologie ( Site 4804)
13353 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +4930450657306» Ansprechpartner anzeigen
Clínica las Condes ( Site 4403)
7591047 Santiago
ChileAbgeschlossen» Google-Maps
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3200)
20133 Milan
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 390223903835» Ansprechpartner anzeigen
Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (
20141 Milano
ItalyAbgeschlossen» Google-Maps
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 3403)
34722 Istanbul
TurkeyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 00905063509061» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

The master protocol is MK-3475-U06.

As of Protocol Amendment 5, the Pembrolizumab Plus MK-4830 Plus Paclitaxel/Irinotecan arm and

the Pembrolizumab Plus MK-4830 Plus Lenvatinib arm are no longer actively enrolling

participants.

Ein-/Ausschlusskriterien

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 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-PD1/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.

- History of human immunodeficiency virus (HIV) infection.

- History of Hepatitis B or known active 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 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)

Studien-Rationale

Primary outcome:

1. Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During Safety Lead-in Phase (Time Frame - Up to approximately 3 weeks):
A DLT is defined as any drug-related AE according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) Version 5.0, observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle.

2. Number of Participants Experiencing Adverse Events (AEs) During Safety Lead-in Phase (Time Frame - Up to approximately 3 weeks):
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

3. Number of Participants Who Discontinue Study Treatment Due to an AE During Safety Lead-in Phase (Time Frame - Up to approximately 3 weeks):
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.

4. Objective Response Rate (ORR) (Time Frame - Up to approximately 92 weeks):
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

Secondary outcome:

1. Progression-Free Survival (PFS) (Time Frame - Up to approximately 189 weeks):
PFS is defined as the time from allocation to the first documented progressive disease (PD) as assessed by RECIST 1.1 or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.

2. Duration of Response (DOR) (Time Frame - Up to approximately 189 weeks):
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.

3. Overall Survival (OS) (Time Frame - Up to approximately 189 weeks):
OS is defined as the time from the date of allocation to death from any cause.

4. Number of Participants Experiencing at Least One Adverse Event (AE) During the Efficacy Phase (Time Frame - Up to approximately 189 weeks):
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

5. Number of Participants Who Discontinue Study Treatment Due to An AE During the Efficacy Phase (Time Frame - Up to approximately 189 weeks):
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Studien-Arme

  • Active Comparator: Paclitaxel or irinotecan
    Participants receive paclitaxel 80-100 mg/m^2 intravenously (IV) on days 1, 8, and 15 every 28-day cycle until progressive disease (PD) or discontinuation, or irinotecan 180 mg/m^2 IV on day 1 of every 14-day cycle until PD or discontinuation.
  • Experimental: Pembrolizumab + MK-4830 + paclitaxel or irinotecan
    Participants receive pembrolizumab 200 mg IV once every 3 weeks (Q3W) for up to 35 cycles (cycle=21 days) or until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + paclitaxel 80-100 mg/m^2 IV on days 1, 8, and 15 every 28-day cycle until PD or discontinuation or irinotecan 180 mg/m^2 180 mg/m^2 on day 1 every 14-day cycle until PD or discontinuation.
  • Experimental: Pembrolizumab + MK-4830 + lenvatinib
    Participants receive pembrolizumab 200 mg IV Q3W up to 35 cycles (cycle=21 days) until PD or discontinuation + MK-4830 800 mg IV Q3W up to 35 infusions + lenvatinib 20 mg oral administration every day until PD or discontinuation.
  • Experimental: Sacituzumab tirumotecan
    Participants will receive 4 mg/kg of sacituzumab tirumotecan via IV infusion on Days 1, 15, and 29 of each 42-day cycle until discontinuation.

Geprüfte Regime

  • Paclitaxel:
    80-100 mg/m2 IV infusion, administered on days 1, 8, and 15 of every 28-day cycle.
  • Irinotecan:
    180 mg/m2 IV infusion, administered on day 1 of every 14-day cycle.
  • Pembrolizumab (MK-3475 / KEYTRUDA® / ):
    200 mg IV infusion, administered every Q3W.
  • MK-4830 (anti-immunoglobulin-like transcript 4 (anti-ILT4)):
    800 mg IV infusion, administered Q3W up to 35 infusions.
  • Lenvatinib (MK-7902 / LENVIMA® / ):
    20 mg oral administration every day.
  • Sacituzumab tirumotecan (SKB264 / MK-2870 / ):
    4 mg/kg IV infusion on Days 1, 15, and 29 of each 42-day cycle.
  • Antihistamine:
    Administered per product label.
  • H2 Receptor Antagonist:
    Administered per product label.
  • Acetaminophen (or equivalent):
    Administered per product label.
  • Dexamethasone (or equivalent):
    Administered per product label.

Quelle: ClinicalTrials.gov


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