First Patient Dosed in Phase 1/2 Trial of HLD-0915 for mCRPC
A phase 1/2 trial is evaluating HLD-0915, a novel oral therapy, for metastatic castration-resistant prostate cancer in up to 80 patients.
Two prostate cancer cells in the final stage of cell division: ©PRB ARTS - stock.adobe.com
A first-in-human, phase 1/2 clinical trial of HLD-0915 (NCT06800313), an investigational bifunctional small molecule therapy, has dosed its first patient with metastatic castration-resistant prostate cancer (mCRPC).1
In the open-label study, experts are evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of HLD-0915 given orally and as a monotherapy for the treatment of patients with mCRPC.2
Up to 80 adult patients with mCRPC whose tumors have progressed on prior systemic therapies are expected to be included in the study that will take place across the US.
“We are very pleased to have initiated the clinical evaluation of HLD-0915 to address the unmet needs of cancer patients with mCRPC,” said Christian Schade, president and chief executive officer of Halda Therapeutics, in a press release.1 “Initiation of this study marks a significant step in advancing our novel small molecule RIPTAC modality as an important new approach for the treatment of cancer.”
About HLD-0915
HLD-0915 is an innovative small molecule therapy designed to selectively target prostate cancer cells by creating a ternary complex between the androgen receptor and an essential effector protein. This mechanism drives the formation of neomorphic protein-protein interactions, disrupting critical cellular functions and inducing an antitumor effect.1
Preclinical studies have shown HLD-0915’s ability to achieve optimal activity and pharmacology by precisely orchestrating interactions between selected proteins.3 In prostate cancer models, oral administration of HLD-0915 resulted in significant tumor shrinkage and reductions in prostate-specific antigen (PSA) levels. Notably, the therapy exhibited a favorable therapeutic index, even in models of drug resistance.
Comparative data highlighted HLD-0915’s superior oral efficacy over enzalutamide (Xtandi) in castrated mouse models with VCaP xenografts, showing its potential as a promising treatment for advanced prostate cancer, including resistant disease.
Behind the Phase 1/2 Trial
The study will consist of 2 parts.2 In phase 1, the dose-escalation part of the study, investigators aim to determine the recommended phase 2 dose to be used in phase 2, the expansion part of the trial. In phase 2, the antitumor activity of HLD-0915 at the recommended expansion doses will be further evaluated.
Enrollment is open to patients aged 18 years and older with confirmed adenocarcinoma of the prostate, progressive mCRPC, and a prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone. An ECOG performance score of 0 to 1, a life expectancy of at least 3 months, and adequate hematological, renal, and hepatic function are all required for those to be included in the trial.
Once enrolled, patients will be given oral HLD-0915 as a single agent on a 21-day cycle until either disease progression or discontinuation of treatment.
Dose-limiting toxicities and the frequency and severity of adverse events (AEs) and serious AEs serve as the primary end points of the study. Secondary end points include evaluating several plasma pharmacokinetic parameters, PSA declines (PSA30, PSA50, and PSA90), objective response rates, and duration of response.
Primary completion of the study is expected in March 2027, and patients are actively being recruited in Michigan and Texas.
REFERENCES:
Halda Therapeutics announces first patient dosed in phase 1/2 clinical trial evaluating HLD-0915 in metastatic castration-resistant prostate cancer. News release. Halda Therapeutics. February 24, 2025. Accessed March 3, 2025. https://tinyurl.com/36azcsae
A study of HLD-0915 in patients with metastatic castration resistant prostate cancer (mCRPC). ClinicalTrials.gov. Last updated February 4, 2025. Accessed March 3, 2025. https://clinicaltrials.gov/study/NCT06800313
Halda Therapeutics presents preclinical data for RIPTAC Therapeutics demonstrating oral efficacy as a monotherapy for the treatment of prostate cancer. News release. Halda Therapeutics. April 17, 2023. Accessed March 3, 2025. https://tinyurl.com/ymwsfxzw
