An open, multicenter phase I study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of MK-6598 as monotherapy and in combination with Pembrolizumab in participants with advanced solid tumors
Descrizione riassuntiva dello studio
The study investigates the safety, tolerability, pharmacokinetics, pharmacodynamics, and effect of MK-6598 alone and combined with Pembrolizumab. "Pharmacokinetics" refers to the absorption, metabolism, and elimination of the substance in the body, among other things. The primary goal of this study is to find the ideal dosage of this substance and to test its safety. Approximately 90 patients are expected to participate in this study worldwide. The actual number of patients will ultimately depend on the results of ongoing investigations and the number of doses examined. These are the two investigational drugs in the study: • Pembrolizumab: In tumor control, the immune system plays an important role. Tumors have certain receptors that prevent the tumor from being recognized by the immune system. Pembrolizumab is an antibody that binds to one of these receptors (PD1 receptor) and inactivates it. This allows the body's natural fight against the tumor to be enhanced by the immune system. Pembrolizumab is already approved in Switzerland and other countries for the treatment of various types of cancer. • MK-6598: The protein IL4I4 is found in the tumor environment and leads to the production of molecules that can prevent the immune system from recognizing the tumor. MK-6598 contains a chemical active ingredient that specifically inhibits the protein IL4I4. This is intended to enhance the body's natural fight against the tumor. In combination with Pembrolizumab, the body's natural fight against the tumor is expected to be further strengthened.
(BASEC)
Intervento studiato
After a thorough eligibility assessment, collection of medical history, and detailed explanation, the participant will be included in the study. Subsequently, the participant will be assigned to one of the following two groups:
Group 1: Receives the drug MK-6598
Group 2: Receives the drugs MK-6598 combined with Pembrolizumab
All study participants receive MK-6598. The dose of MK-6598 administered depends on the timing of enrollment in the study. Participants assigned to Group 1 (MK-6598 only) may potentially switch to Group 2 (MK-6598 combined with Pembrolizumab) if their cancer condition worsens and they meet the necessary requirements. If participants develop intolerances to MK-6598, they cannot continue to be treated in Group 2 and will be excluded from the study.
This study is an open-label study, meaning that both the physician and the participants themselves know which treatment they have been assigned.
MK-6598 is a tablet and is taken orally (swallowed). Participants in Group 1 take the drug MK-6598 daily and come to the study center for control visits every 3 weeks during the treatment period (more often at the beginning).
Participants in Group 2 receive, in addition to the daily intake of MK-6598, an intravenous infusion of Pembrolizumab every 3 weeks during their visit to the study center. The duration of treatment with Pembrolizumab is limited to 2 years (35 administrations).
During study visits, various measures and examinations may take place, including: discussion of well-being and current medication, questioning about daily activities and any restrictions regarding them, administration/handing out of study medication, heart examinations (electrocardiogram (ECG), multiple samples of blood, urine, or tissue, physical examination including checking vital signs (pulse, blood pressure, etc.). Additionally, two tumor biopsies will be performed during the study, one before treatment begins and another 3 weeks after treatment starts.
During and after the treatment phase, health status will be regularly monitored for any potential progression of the cancer using imaging studies (for example, CT and/or MRI scans). In case of disease worsening, participants will visit the study center at least one more time for safety follow-up visits. Subsequently, participants will be contacted by phone approximately every 12 weeks.
(BASEC)
Malattie studiate
For cancer patients suffering from an advanced solid tumor that cannot be treated with approved medications or therapies, there are often limited treatment options. This study investigates a novel substance (MK-6598) that has never been tested in humans, either alone or in combination with an approved medication, and aims to study the safety of MK-6598, find the recommended dosages of MK-6598, and measure what happens when MK-6598 passes through the body. This new substance has been tested so far in laboratory models and on animals, but never in humans. Adult male and female participants with advanced or metastatic solid (firm) tumors who have already received all approved treatment options will be included. Participants must be in good general health and meet certain laboratory values to participate in the study. The laboratory values must reflect adequate organ function (for example, of the blood system, kidneys, and liver).
(BASEC)
• Patients with a confirmed diagnosis of advanced or metastatic solid tumor. Patients must have already received or not tolerated all treatments known to provide clinical benefit. • Patients must still be in good general health. • One or more malignant lesions must be present that are accessible for at least two separate biopsies. The investigator will assess at the beginning of the study whether the biopsy of such lesions is medically safe. (BASEC)
Criteri di esclusione
• Treatment with chemotherapeutics, radiotherapy, or biological cancer therapy within the last 4 weeks prior to the first dose of the study intervention (2 weeks for palliative radiotherapy). • History of a second malignancy, unless successful treatment was completed without signs of recurrence for 2 years. • Active metastasis of the CNS (central nervous system) and/or carcinomatous meningitis (inflammatory reaction due to cancer spread to the meninges). (BASEC)
Luogo dello studio
Bellinzona, Ginevra, San Gallo
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Luzern
(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, Luzern
(BASEC)
Informazioni generali
Merck Sharp & Dohme LLC
(ICTRP)
Informazioni generali
Merck Sharp & Dohme LLC
(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica Ticino
(BASEC)
Data di approvazione del comitato etico
13.12.2022
(BASEC)
ID di studio ICTRP
NCT05594043 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A Phase 1, Open-label, Multicenter Study to Assess Safety, Tolerability, PK, and Efficacy of MK-6598 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (BASEC)
Titolo accademico
A Phase 1, Open-label, Multicenter Study to Assess Safety, Tolerability, PK, and Efficacy of MK-6598 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (ICTRP)
Titolo pubblico
A Study of MK-6598 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Advanced Solid Tumors (MK-6598-001) (ICTRP)
Malattie studiate
Advanced or Metastatic Solid Tumors (ICTRP)
Intervento studiato
Drug: MK-6598Biological: Pembrolizumab (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Criteri di inclusione/esclusione
Inclusion Criteria:
- Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor by
pathology report and has received, or been intolerant to, all treatment known to
confer clinical benefit.
- Has measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
as assessed by the local site investigator/radiology.
- Has one or more discrete malignant lesions that are amenable to a minimum of 2
separate biopsies.
- Has a baseline tumor sample that can be submitted for analysis.
- Human immunodeficiency virus (HIV)-infected participants must have well controlled
HIV on antiretroviral therapy (ART).
- A participant assigned male sex at birth who receives MK-6598 must agree to use
contraception and should refrain from donating sperm during the specified period(s)
of at least 102 days after study interventions.
- A participant assigned female sex at birth is eligible to participate if not
pregnant or breastfeeding and at least 1 of the following: not a participant of
childbearing potential (POCBP) or a POCBP who agrees to follow the contraceptive
guidance during the treatment period and for up to 120 days after study
intervention.
Exclusion Criteria:
- Received prior systemic anticancer therapy including investigational agents within 4
weeks before the first dose of study intervention or has not recovered to CTCAE
Version 5.0 Grade 1 or better from any AEs that were due to cancer therapeutics
administered more than 4 weeks earlier (this includes participants with previous
immunomodulatory therapy with residual immune-related AEs).
- Known additional malignancy that is progressing or has required active treatment
within 2 years.
- Clinically active central nervous system (CNS) metastases and/or carcinomatous
meningitis.
- A severe hypersensitivity (=Grade 3) reaction to treatment with a monoclonal
antibody/components of the study intervention.
- Active infection requiring therapy.
- History of interstitial lung disease.
- History of (noninfectious) pneumonitis that required steroids or current
pneumonitis.
- Active autoimmune disease that has required systemic treatment in the past 2 years.
Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is
allowed.
- Has known hepatitis B or C infections or known to be positive for hepatitis B
surface antigen (HBsAg)/hepatitis B virus (HBV) deoxyribonucleic acid (DNA) or
hepatitis C antibody or ribonucleic acid (RNA).
- Has a history or current evidence of any condition, therapy, laboratory abnormality,
or other circumstance that might confound the results of the study or interfere with
the participant's participation for the full duration of the study, such that it is
not in the best interest of the participant to participate, in the opinion of the
treating investigator.
- Received prior radiotherapy within 2 weeks of start of study intervention, has
radiation-related toxicities requiring corticosteroids, or had a history of
radiation pneumonitis.
- Has received a live or live-attenuated vaccine within 30 days before the first dose
of study intervention. Administration of killed vaccines are allowed.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,
cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137), and was
discontinued from that treatment due to a =Grade 3 immune-related AE (irAE).
- 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 before the start of study treatment.
- Has had an allogeneic tissue/solid organ transplant in the last 5 years or has
evidence of graft-versus-host disease. (ICTRP)
non disponibile
Endpoint primari e secondari
Number of Participants with a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 5.0;Number of Participants Who Experience At Least One AE;Number of Participants Who Discontinue Study Treatment Due to an AE (ICTRP)
Area Under the Curve (AUC) of MK-6598;Minimum Serum Concentration (Cmin) of MK-6598;Maximum Serum Concentration (Cmax) of MK-6598;Tumor Phenylpyruvate Concentrations (ICTRP)
Data di registrazione
21.10.2022 (ICTRP)
Inclusione del primo partecipante
non disponibile
Sponsor secondari
non disponibile
Contatti aggiuntivi
Medical Director, Merck Sharp & Dohme LLC (ICTRP)
ID secondari
MK-6598-001, 6598-001 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT05594043 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile