HLD-0915 Earns FDA Fast Track Designation in Metastatic CRPC

HLD-0915 is engineered by developers as a bifunctional small molecule therapy holding together a tumor-specific intracellular targeting protein and effector protein to selectively target prostate cancer tumor cells.

The FDA has granted fast track designation to HLD-0915 for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC), according to a news release from the drug’s developer, Halda Therapeutics.¹

Additionally, the developers are currently enrolling patients on a first-in-human phase 1/2 clinical trial (NCT06800313) to evaluate the safety and tolerability of HLD-0915 in metastatic CRPC. The study is composed of a phase 1 dose-escalation portion to determine the maximum tolerated dose (MTD) and/or recommended expansion doses of HLD-0915 monotherapy as well as a phase 2 expansion portion to further evaluate the agent’s efficacy and safety.

“We are pleased HLD-0915 has been granted fast track designation by [the] FDA for patients with [metastatic] CRPC,” Christian Schade, president and chief executive officer of Halda Therapeutics, said in the news release.¹ “Fast track designation is an important step forward as we work to advance this program through clinical development and, ultimately, to bring a novel, highly selective, oral-based treatment option to patients living with this challenging disease.”

Patients in the phase 1/2 trial will undergo 21-day treatment cycles with oral HLD-0915 given as monotherapy.² Treatment may continue until disease progression, withdrawal of consent, intercurrent illness, unacceptable toxicities, or other discontinuation criteria.

The phase 1 portion of the trial will utilize a Backfill Bayesian Optimal Interval (BF-BOIN) design, which will enable backfilling patients to doses of the study drug that are cleared for safety during dose escalation, facilitating additional generation of safety, tolerability, and preliminary efficacy data on doses beneath the MTD. Cohort sizes will include 3 patients with enrollment staggered between cohorts.

The antitumor activity of HLD-0915 will be assessed in the phase 2 portion of the trial at the recommended doses for expansion in this patient population. The design and population will be determined based on the outcomes of the phase 1 portion of the trial.

HLD-0915 is engineered by developers as a bifunctional small molecule therapy holding together a tumor-specific intracellular targeting protein and effector protein to selectively target prostate cancer tumor cells. Bypassing an essential function within cancer cells, the agent’s ternary complex drives the formation of neomorphic protein-protein interactions, resulting in an antitumor effect. Preclinical prostate cancer models revealed that oral HLD-0915 resulted in reductions in tumor size as well as prostate-specific antigen (PSA).

The coprimary end points of the phase 1 portion of the trial are dose-limiting toxicities and the frequency and severity of adverse effects. Secondary end points include plasma concentrations, pharmacokinetics, PSA decline, objective response rate, duration of response, radiographic progression-free survival, and time to response.

Those eligible for enrollment include patients 18 years and older with histologically, pathologically, and/or cytologically confirmed adenocarcinoma of the prostate. Patients must additionally have had a prior orchiectomy and/or ongoing androgen-deprivation therapy; have experienced progression on a prior line of therapy; an ECOG performance status score of 0 to 1; a life expectancy of at least 3 months; and adequate hematological, renal, and hepatic function.

Furthermore, exclusion criteria include those with a recent major bleed or a known bleeding disorder, those with tumors exhibiting neuroendocrine or small cell carcinoma histology, and those receiving continuous corticosteroids at prednisone-equivalent dose of more than 10 mg per day. Those who have received systemic anti-cancer therapies or investigational drugs within 2 weeks of first study dose; a history of myocardial infarction or unstable angina within 6 months before enrollment; known clinically significant active or chronic infection; and acute or chronic uncontrolled renal disease, pancreatitis, or liver disease were also excluded from trial enrollment.

References

1. Halda Therapeutics receives FDA fast track designation for HLD-0915 for the treatment of metastatic castration-resistant prostate cancer. News release. Halda Therapeutics. August 14, 2025. Accessed August 14, 2025. https://tinyurl.com/3rrzwzv5
2. A study of HLD-0915 in patients with metastatic castration resistant prostate cancer (mCRPC). ClinicalTrials.gov. Updated April 16, 2025. Accessed August 14, 2025. https://tinyurl.com/ysdsszrw