Phase 1/2 trial launches of first-in-class RIPTAC therapeutic in mCRPC

The first patient has been dosed in a phase 1/2 clinical trial (NCT06800313) evaluating the investigational bifunctional small molecule therapy HLD-0915 in patients with metastatic castration-resistant prostate cancer (mCRPC), Halda Therapeutics announced in a news release.¹

Primary completion is expected in March 2027.

According to the company, HLD-0915 is part of a new class of small molecule cancer therapies called RIPTAC (Regulated Induced Proximity TArgeting Chimeras) therapeutics. The company is also developing a RIPTAC therapeutic for hormone receptor positive metastatic breast cancer, with additional RIPTACS in development.²

“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 CEO of Halda Therapeutics, in the news 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.”

Overall, the trial is assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of oral HLD-0915 monotherapy in patients with mCRPC.³ The phase 1 portion of the study will involve dose escalation to find the recommended phase 2 dose for expansion. Phase 2 will further assess the anti-tumor activity of HLD-0915 at the recommended expansion doses.

In total, the phase 1/2, open-label trial plans to enroll up to 80 adult patients with mCRPC whose tumors have progressed on prior systemic therapies. Participants will be enrolled through clinical trial sites across the US.

To be eligible for enrollment, patients need to have confirmed adenocarcinoma of the prostate, progressive mCRPC, and a prior orchiectomy and/or ongoing androgen deprivation therapy and a castrate level of serum testosterone. Patients must also have an ECOG performance score of 0 to 1, a life expectancy of at least 3 months, and adequate hematological, renal, and hepatic function.

For the study, patients with receive oral HLD-0915 as a single agent on a 21-day cycle until disease progression or treatment discontinuation.

The primary end points include dose-limiting toxicities and the frequency and severity of adverse events and serious adverse events. As secondary outcome measures, the study will also assess several plasma pharmacokinetic parameters, prostate-specific antigen (PSA) declines (PSA30, PSA50, and PSA90), objective response rates, and duration of response, among other measures.

Primary completion of the study is expected in March 2027.

Additional information on HLD-0915

According to Halda Therapeutics, RIPTAC therapies are “designed to selectively target prostate cancer tumors cells by holding together, with defined orientation and purpose, androgen receptor (a tumor-specific intracellular targeting protein) and a protein with essential function (effector protein).” This leads to the formation of new protein-protein interactions, which then dissolves an essential function of cancer cells, leading to anti-tumor activity.

Preclinical data showed that treatment with HLD-0915 led to tumor shrinkage and PSA decline, “while delivering a favorable therapeutic index including in models of drug resistance,” the company reported. Data also suggested superior oral efficacy of multiple RIPTACs to enzalutamide in in vivo castrated mice models bearing VCaP xenografts.⁴

References

1. 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. Published online and accessed February 24, 2025. https://haldatx.com/halda-therapeutics-announces-first-patient-dosed-in-phase-1-2-clinical-trial-evaluating-hld-0915-in-metastatic-castration-resistant-prostate-cancer/

2. View our pipeline. Halda Therapeutics. Accessed February 24, 2025. https://haldatx.com/our-pipeline/

3. A study of HLD-0915 in patients with metastatic castration resistant prostate cancer (mCRPC). ClinicalTrials.gov. Last updated February 4, 2025. Accessed February 24, 2025. https://clinicaltrials.gov/study/NCT06800313

4. 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 February 24, 2025. https://haldatx.com/halda-therapeutics-presents-preclinical-data-for-riptac-therapeutics-demonstrating-oral-efficacy-as-a-monotherapy-for-the-treatment-of-prostate-cancer/