Novartis Pharmaceuticals
The purpose of this study is to evaluate the safety, tolerability, and efficacy of two different treatment combinations of tulmimetostat in participants with de novo or recurrent metastatic hormone-sensitive prostate cancer (mHSPC). Phase I aims to determine the recommended dose(s) for expansion (RDE) of tulmimetostat in combination with darolutamide or abiraterone. Phase II is designed to further evaluate the efficacy and safety of tulmimetostat in combination with darolutamide compared with darolutamide alone in participants with mHSPC.
This is a Phase I/II, open-label, global, multicenter study evaluating tulmimetostat in combination with androgen receptor pathway inhibitors in participants with de novo or recurrent metastatic hormone-sensitive prostate cancer (mHSPC). The study consists of two phases: Phase I (Dose Escalation) Phase I includes two treatment groups: 1. Group A (Part 1): tulmimetostat in combination with darolutamide. 2. Group B (Part 2): tulmimetostat in combination with abiraterone. The primary objective of Phase I is to determine the recommended dose(s) for expansion (RDE) of tulmimetostat in each comb…
Key Inclusion Criteria: * Adult men ≥ 18 years old with de novo or recurrent mHSPC (without neuroendocrine or small cell features). The tumor lesion(s) may be located in the bone, soft tissue/visceral region, or both. * Participants must have castrate levels of testosterone, i.e., ≤ 50 ng/dL (≤ 1.7 nM). * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * Adequate bone marrow and organ function * Prior ADT: Participants must have started ADT at least 1 month (at least 28 days) but no more than 12 months before study entry and be willing to continue ADT during treatment * Pr…
Tulmimetostat is an oral dual EZH1/EZH2 inhibitor administered once daily. In Phase I, escalating dose levels will be evaluated in combination with darolutamide or abiraterone. In Phase II, one or two dose levels selected from Phase I will be evaluated in combination with darolutamide.
Darolutamide 600 mg administered orally twice daily (BID).
Abiraterone 1000 mg administered orally once daily (QD) in combination with prednisone/prednisolone according to local prescribing information.
Oral corticosteroid administered with abiraterone in Phase I Group B according to local prescribing information.
Background therapy consisting of a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior orchiectomy to maintain castrate testosterone levels (\<50 ng/dL \[\<1.7 nmol/L\]). All participants will continue ADT throughout study participation.