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

Zusammenfassung der Studie

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)

Untersuchte Intervention

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)

Untersuchte Krankheit(en)

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)

Sponsor

Amgen Inc. Thousand Oaks, CA, USA Amgen Switzerland AG, Rotkreuz

(BASEC)

Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Genf

(BASEC)

Datum der Bewilligung durch die Ethikkommission

13.06.2022

(BASEC)

Ergebnisse der Studie