The first patient has been dosed in the first-in-human phase 1/2 clinical trial, which is evaluating HLD-0915, a part of a novel class of cancer therapies called RIPTACT (Regulated Induced Proximity TArgeting Chimeras) therapeutics, for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC), according to a press release from Halda Therapeutics.
“We are very pleased to have initiated the clinical evaluation of HLD-0915 to address the unmet needs of patients with mCRPC,” Christian Schade, president and chief executive officer of Halda Therapeutics, stated in the news release. “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.”
HLD-0915 is a bifunctional small molecule therapy engineered to selectively target prostate cancer cells by linking the androgen receptor — a tumor-specific intracellular target — with an effector protein in a precise orientation. This then disrupts critical cancer cell functions, leading to an antitumor effect.
The agent is designed to promote specific protein interactions for optimal activity and pharmacological properties; it has demonstrated results in previous preclinical studies. Furthermore, in preclinical prostate cancer models, oral administration of HLD-0915 led to tumor reduction and decreased prostate-specific antigen (PSA) levels while maintaining a favorable therapeutic index, including in drug-resistant models, according to the press release.
Understanding the Phase 1/2 Investigation of HLD-0915
The press release states that this is a phase 1/2 multi-center clinical trial which is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of single-agent HLD-0915 orally administered in patients with mCRPC. In the initial phase 1 dose escalation portion of the study, investigators aim to determine the maximum tolerated dose and/or recommended dose for expansion of HLD-0915 as monotherapy, whereas the phase 2 expansion cohort will further evaluate the efficacy and safety of HLD-0915. Up to 80 patients with mCRPC could be enrolled onto the clinical trial.
According the ClinicalTrials.gov page which houses all the information for the phase 1/2 trial, unless surgically castrated, all patients on the study must continue androgen deprivation therapy. The informational page goes on to state additional eligibility criteria for the trial. To qualify for participation in the phase 1 study, male patients must aged 18 years or older and have histological, pathological or cytological confirmation of prostate adenocarcinoma. Additionally, patients must have progressive mCRPC with PSA progression, with or without radiographic progression, after prior lines of therapy. An ECOG performance status of 0 to 1 and a life expectancy of at least three months are required. Patients must also have adequate hematologic, renal and hepatic function, be able to swallow oral medication, and commit to study visits and protocol requirements.
Contrarily, certain conditions will exclude patients from participation in the ongoing trial. Individuals with a recent major bleed or a known bleeding disorder, tumors with a neuroendocrine or small cell carcinoma component, or those on continuous corticosteroids exceeding a prednisone-equivalent dose of 10 milligrams a day will not qualify for enrollment. Additionally, patients who have received systemic anti-cancer therapy or investigational drugs within two weeks before the first study dose — with exceptions requiring longer washout periods — are ineligible.
A history of myocardial infarction or unstable angina within six months prior to enrollment, significant cardiac disease, or clinically significant active or chronic infections also will also be excluded from the trial. Finally, patients with acute or chronic uncontrolled renal disease, pancreatitis or liver disease will not be eligible for study participation.
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