Dr Qin on the Design of the HARMONY Trial of Niraparib-Based Therapy in mHSPC

"The HARMONY trial...is more of an adaptive trial that allows patient to have a choice [of treatment] based on their PSA response."

Qian (Janie) Qin, MD, an assistant professor in the Department of Internal Medicine at the University of Texas Southwestern Medical Center and the Eugene P. Frenkel, MD, Scholar in Clinical Medicine at the Harold C. Simmons Comprehensive Cancer Center, discussed the unique aspects of the design of the phase 2 HARMONY trial (NCT06392841) investigating ​niraparib (Zejula) plus abiraterone acetate (Zytiga) and prednisone in patients with treatment-naive metastatic hormone-sensitive prostate cancer (mHSPC) with deleterious homologous recombination repair (HRR) alterations.

The HARMONY trial uses an adaptive clinical study design that incorporates patient choice based on prostate-specific antigen (PSA) response dynamics, Qin began. This trial structure allows treatment to be tailored according to early biomarkers of response, she noted. The investigational therapeutic backbone under evaluation in this trial is composed of the same agents evaluated in the investigational arm of the phase 3 AMPLITUDE trial (NCT04497844) in patients with metastatic castration-sensitive prostate cancer. In HARMONY, all patients will initially receive ADT in combination with niraparib during a 24-week induction phase. PSA kinetics during this period will guide subsequent treatment decisions, she explained.

For patients who do not achieve an optimal PSA level decline—defined as PSA levels remaining above 4 ng/mL without radiographic or clinical progression—treatment intensification is permitted. These patients may either continue the triplet regimen of ADT plus abiraterone and niraparib or transition to an alternative triplet strategy by discontinuing niraparib and adding docetaxel to ADT and abiraterone. This approach allows for escalation of therapy in cases of suboptimal biochemical response, Qin emphasized.

Conversely, patients achieving PSA level reduction to 4 ng/mL or lower at the 24-week mark are eligible to continue to receive the niraparib-based triplet regimen for a total of 1 year. At the 12-month time point, treatment is further stratified. Patients achieving deep PSA level suppression to less than 0.2 ng/mL may choose either to discontinue therapy—a de-escalation strategy—or maintain treatment, Qin highlighted. Patients with PSA levels of at least 0.2 ng/mL will be advised to continue to receive the niraparib-based triplet until disease progression or unacceptable toxicity, for a maximum duration of 2 years.

An additional distinguishing feature of the HARMONY trial is its intentional prioritization of enrollment among historically underrepresented populations in prostate cancer research, according to Qin. Prior pivotal phase 3 trials leading to current standard-of-care therapies for patients with prostate cancer included disproportionately low numbers of racial and ethnic minority patients, with African American men comprising fewer than 3% to 5% of patients and Hispanic/Latino men comprising fewer than 10% to 15% of enrolled patients, she stated. HARMONY is specifically designed to increase participation of non-Hispanic Black and Hispanic/Latino patients, she emphasized. The goal is to elucidate potential differences in HRR alterations, therapeutic response, and toxicity profiles between these populations, thereby generating more inclusive and clinically relevant data to inform precision medicine approaches in prostate cancer care, she concluded.