A Phase 1/1b/2 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AMG 193 alone and in combination with Docetaxel in patients with advanced solid methylthioadenosine phosphorylase (MTAP)-null tumors
Descrizione riassuntiva dello studio
This project is being conducted to test the efficacy (how well something works), tolerability (how the study drug feels), and safety of the tested preparation/drug AMG 193 alone and in combination with Docetaxel for the treatment of advanced solid tumors with MTAP loss. The study will include patients with advanced cancer who have a DNA alteration, either the loss of methylthioadenosine phosphorylase (MTAP) or the loss of cyclin-dependent kinase inhibitor 2A (CDKN2A), which can restrict the functioning of the enzyme protein-arginine-methyltransferase 5 (PRMT5) in your cancer. Protein-arginine-methyltransferase 5 is important for the survival of cancer cells, and AMG 193 is a PRMT5 inhibitor that may interact with the DNA alteration in your cancer cells to further inhibit PRMT5 and thus kill the cancer. In the lab, AMG 193 inhibits PRMT5 activity in cancer cells with MTAP loss and selectively kills them.
(BASEC)
Intervento studiato
The study will consist of 2 parts: Part 1 and Part 2: In Part 1 and Part 2, it will be investigated which doses of AMG 193 alone or in combination with Docetaxel are safe for people with metastatic or locally advanced solid tumors without methylthioadenosine phosphorylase (MTAP). The study will also evaluate the anticancer effect of AMG 193 alone or in combination with Docetaxel in patients with solid tumors without MTAP. Part 1 consists of parts 1a to 1h, where AMG 193 is administered as a single agent. In parts 1a and 1b, it will be investigated which doses of AMG 193 are safe for patients. In parts 1c to 1h, the safe dose determined in parts 1a and 1b will be confirmed across different cancer types and it will be determined whether AMG 193 is effective against the various cancer types. Part 2 consists of parts 2a and 2b, where AMG 193 is administered in combination with Docetaxel. The study will include approximately 340 participants, of whom 290 individuals will be included in Part 1 and 50 individuals in Part 2 of the study, coming from approximately 50 hospitals/facilities in North America, Canada, Europe, and the Asia-Pacific region. In Switzerland, approximately 28 participants will be recruited over a period of 22 months (so-called "recruitment period"), and the total duration of study participation for each participant is expected to be 2 years. During the study, approximately 12 to 15 visits to the clinic will take place. Additionally, you will be contacted by phone as needed throughout the study period to check on your well-being. All participants who meet the study requirements and are enrolled in the study will receive AMG 193 as part of this study.
(BASEC)
Malattie studiate
You are suffering from an advanced tumor that has an altered DNA: either a loss of methylthioadenosine phosphorylase (MTAP) or a loss of cyclin-dependent kinase inhibitor 2A (CDKN2A). This study aims to investigate whether AMG 193 alone or in combination with Docetaxel represents a safe and effective treatment option for advanced solid tumors with MTAP loss.
(BASEC)
- The subject has provided informed consent prior to the initiation of any study-specific activities/procedures. - Age ≥ 18 years. - Evidence of a homozygous loss of CDKN2A (null) and/or MTAP (null) or lost MTAP expression in tumor tissue. - Histologically confirmed metastatic or locally advanced solid tumor that is not amenable to curative treatment by surgery and/or radiation therapy. - Participants must be able to swallow and retain the study treatment administered orally and be willing to document daily intake of the investigational product. (BASEC)
Criteri di esclusione
- Spinal cord compression or active brain metastases or leptomeningeal disease due to non-brain tumors. Subjects who have had brain metastases resected or who have received radiation therapy that ended at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) remaining neurological symptoms grade ≤ 2; b) stable doses of dexamethasone if applicable; and c) follow-up MRI within 30 days of day 1 showing no new lesions. - Presence of a primary brain tumor. - Presence of a hematological malignancy or lymphoma. - Signs of current interstitial lung disease or pneumonitis or a prior history of interstitial lung disease or non-infectious pneumonitis. (BASEC)
Luogo dello studio
Bellinzona, Berna, Ginevra
(BASEC)
Sponsor
Amgen Inc. Thousand Oaks, CA, USA Amgen Switzerland AG, Rotkreuz
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Dr. med. Alfredo Addeo
+41 22 372 98 62
alfredo.addeo@clutterhcuge.chHôpitaux Universitaire Genève (HUG), Département d’Oncologie
(BASEC)
Informazioni scientifiche
non disponibile
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica Ginevra
(BASEC)
Data di approvazione del comitato etico
13.06.2022
(BASEC)
ID di studio ICTRP
non disponibile
Titolo ufficiale (approvato dal comitato etico)
Eine Phase-1/1b/2-Studie zur Bewertung der Sicherheit, Verträglichkeit, Pharmakokinetik, Pharmakodynamik und Wirksamkeit von AMG 193 allein und in Kombination mit Docetaxel bei Patienten mit fortgeschrittenen soliden Methylthioadenosinphosphorylase (MTAP)-null-Tumoren (BASEC)
Titolo accademico
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Intervento studiato
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Tipo di studio
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Criteri di inclusione/esclusione
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Endpoint primari e secondari
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Data di registrazione
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Inclusione del primo partecipante
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Risultati-Dati individuali dei partecipanti
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Ulteriori informazioni sullo studio
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Risultati dello studio
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