Andrew Laccetti, MD, MS, discusses results from a phase 1 trial of masofaniten monotherapy in patients with metastatic castration-resistant prostate cancer and highlights the rationale for launching a phase 1/2 study evaluating masofaniten in combination with enzalutamide vs enzalutamide alone in this patient population.
Andrew Laccetti, MD, MS, medical oncologist, assistant attending, Genitourinary Medical Oncology, Memorial Sloan Kettering Cancer Center, discusses results from a phase 1 trial (NCT04421222) of masofaniten (EPI-7386) monotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC) and highlights the rationale for launching a phase 1/2 study (NCT05075577) evaluating masofaniten in combination with enzalutamide (Xtandi) vs enzalutamide alone in this patient population.
The single-arm, first-in-human, phase 1 trial with masofaniten monotherapy has been discussed at prior medical meetings, Laccetti begins. This study aimed to determine the ideal monotherapy dosage for the agent and assess its safety, toxicity, and initial efficacy. In the trial, this agent was highly tolerable across all tested dose levels, with adverse effects (AEs) largely resembling those of other androgen receptor (AR) antagonists and androgen deprivation therapy (ADT), Laccetti explains. These include AEs such as fatigue and hot flashes. Although a minority of patients experienced gastrointestinal AEs such as diarrhea, the overall safety profile of masofaniten closely aligns with that of ADT and other AR pathway inhibitors, he notes.
Accordingly, oncologists remain optimistic regarding the continued tolerability of masofaniten, Laccetti continues. Specific patient groups have experienced early indications of positive responses, fueling the ongoing investigation of the agent and its use in a broader patient population, he emphasizes.
Furthermore, the phase 1/2 trial investigating the combination of masofaniten and enzalutamide represents another significant step in human clinical research, Laccetti continues. Preclinical evidence strongly supports the idea that this combination could offer enhanced treatment efficacy compared with that elicited by either agent alone, he says, noting that these data are from preclinical studies and require further exploration in human trials. The rationale behind this investigation is that this approach may delay or reduce the development of resistance mechanisms, he explains. The primary goal of the combination study is to establish the safety of using masofaniten and enzalutamide together and determine the recommended dosage for both after considering the potential for pharmacokinetic interactions between these 2 drugs, Laccetti concludes.