HLD-0915 for Prostate Cancer

Recruiting at 10 trial locations

Overseen By Medical Monitor

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Halda Therapeutics OpCo, Inc.

Must be taking: Bisphosphonates, Denosumab

Must not be taking: Corticosteroids, Chemotherapy

Disqualifiers: Bleeding disorder, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called HLD-0915, an experimental drug for prostate cancer that has spread and resisted other treatments. The aim is to assess the safety and effectiveness of this drug when used alone. Men whose prostate cancer has worsened despite previous therapies and who have undergone surgical or medical procedures to lower testosterone may be suitable candidates. The trial involves taking an oral medication every 21 days. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must not have received certain cancer treatments or investigational drugs within 2 weeks before starting the study drug. Some treatments may require a longer period without them before joining the trial.

Is there any evidence suggesting that HLD-0915 is likely to be safe for humans?

Research has shown that HLD-0915 is generally easy for patients to handle. Early studies suggested that this pill is safe to use. Reports indicated that patients did not experience serious side effects, and the treatment showed early signs of helping to fight prostate cancer. These results are encouraging for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for prostate cancer, which often include hormone therapy, radiation, or surgery, HLD-0915 is unique because it is an oral medication administered as a single agent on a 21-day cycle. Researchers are excited about HLD-0915 because it offers a potentially less invasive option with a novel mechanism of action, which could provide a more convenient treatment alternative for patients. This new approach might also lead to fewer side effects compared to traditional therapies, which can significantly impact the quality of life.

What evidence suggests that HLD-0915 might be an effective treatment for prostate cancer?

Research has shown that HLD-0915, the investigational treatment in this trial, shows early signs of effectiveness in treating metastatic castration-resistant prostate cancer (mCRPC). Initial findings suggest that patients found this pill easy to take, and it showed promise in slowing cancer cell growth. In previous studies, patients who had tried other treatments responded positively to HLD-0915. This suggests HLD-0915 could be an option for those whose cancer did not respond to other therapies. While more research is needed, these early results offer encouragement for those considering this treatment. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic castration-resistant prostate cancer (mCRPC) who have already tried other systemic therapies. Participants should meet specific health criteria set by the researchers.

Inclusion Criteria

Willing and able to adhere to the study visit schedule and other protocol requirements

My prostate cancer diagnosis was confirmed through lab tests.

Life expectancy of at least 3 months

Exclusion Criteria

I have had a major bleeding event recently or have a bleeding disorder.

My tumor shows signs of neuroendocrine or small cell features under the microscope.

I haven't had cancer treatment or experimental drugs in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose-escalation and cohort expansion to determine the maximum tolerated dose and recommended dose for expansion of HLD-0915

21 days per cycle

Multiple visits per cycle for dose-escalation and monitoring

Phase 2 Treatment

Evaluation of anti-tumor activity of HLD-0915 at recommended dose for expansion

21 days per cycle

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HLD-0915

Trial Overview

The study is testing HLD-0915 as a solo treatment to see how safe and effective it is for mCRPC patients after establishing an appropriate dose in the first phase of the trial.

How Is the Trial Designed?

Group I: HLD-0915 Experimental Treatment 1 Intervention

Oral HLD-0915 administered as a single agent on a 21-day treatment cycle.

Who Is Running the Clinical Trial?

Halda Therapeutics OpCo, Inc.

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study of 879 patients with metastatic prostate cancer, BRCA2, ATM, and CDK12 were identified as the most frequently disrupted DNA damage repair genes, found in 15% of cases, indicating potential therapeutic vulnerabilities.

The presence of BRCA2 and CDK12 mutations was linked to poorer clinical outcomes, while the stability of these mutations in both plasma cell-free DNA and archival tissues suggests that ctDNA could be a valuable diagnostic tool for monitoring disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRCA2, ATM, and CDK12 Defects Differentially Shape Prostate Tumor Driver Genomics and Clinical Aggression. Warner, E., Herberts, C., Fu, S., et al.[2022]

In a study of 36 patients with locally advanced prostate cancer and germline DNA damage repair gene defects, the combination of docetaxel and cisplatin chemotherapy showed a significant improvement in biochemical progression-free survival compared to docetaxel alone, with a median bPFS not reached in the cisplatin group versus 7.76 months in the docetaxel group.

The docetaxel plus cisplatin group also demonstrated a higher rate of tumor down-staging (78.57%) compared to the docetaxel group (40.9%), indicating enhanced efficacy, while maintaining a tolerable safety profile with only one case of severe liver insufficiency due to viral hepatitis A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant docetaxel + cisplatin chemo-hormonal therapy versus docetaxel chemo-hormonal therapy in patients with locally advanced prostate cancer with germline DNA damage repair gene alterations. Chi, C., Liu, J., Fan, L., et al.[2022]

The study identified PSMA(27) as the most effective peptide for binding to HLA-A2 molecules on dendritic cells, suggesting its potential as a key component in prostate cancer vaccines.

This research is significant as it provides the first evaluation of PSMA peptides based on their binding efficiency to dendritic cells, paving the way for future clinical applications in HLA-A2 positive prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binding of prostate-specific membrane antigen to dendritic cells: a critical step in vaccine preparation. Garetto, S., Sizzano, F., Brusa, D., et al.[2018]

The study developed a prostate-restricted replicative adenovirus (AdIU3) that delivers Fas ligand (FasL) specifically to prostate cancer cells, enhancing its antitumor effects while significantly reducing systemic toxicity compared to traditional methods.

AdIU3 effectively induced apoptosis in prostate cancer cells without harming normal cells, and systemic administration showed no detectable toxicity, unlike the control virus which caused severe harm, demonstrating a safer approach to cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fas ligand delivery by a prostate-restricted replicative adenovirus enhances safety and antitumor efficacy. Li, X., Liu, YH., Zhang, YP., et al.[2018]

The CDCA1 peptide vaccine was well tolerated in a phase I trial with 12 patients suffering from castration-resistant prostate cancer (CRPC), showing no serious adverse events, which highlights its safety profile.

The vaccine induced specific immune responses in patients, with a median overall survival of 11 months, suggesting that it may effectively stimulate the immune system to target CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination for castration resistant prostate cancer. Obara, W., Sato, F., Takeda, K., et al.[2021]

The novel human gene HSDL1, located on chromosome 16q24.2, encodes a protein related to 17beta-HSD3 and is highly expressed in reproductive tissues like the testis and ovary.

HSDL1 expression is significantly increased in prostate cancer tissues compared to normal prostate tissues, indicating its potential role in the development of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel human hydroxysteroid dehydrogenase like 1 gene (HSDL1) is highly expressed in reproductive tissues. Huang, Y., Tang, R., Dai, J., et al.[2019]

In a study of 127 high-risk prostate cancer patients, high expression of PDL1 was found to be common and significantly associated with poorer outcomes, including shorter time to biochemical recurrence (BCR) after treatment.

PDL1 expression serves as an independent prognostic biomarker for high-risk prostate cancer, suggesting that targeting the PD1/PDL1 pathway could be a promising adjuvant therapy following radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Immune Checkpoint Regulator PDL1 is an Independent Prognostic Biomarker for Biochemical Recurrence in Prostate Cancer Patients Following Adjuvant Hormonal Therapy. Li, H., Wang, Z., Zhang, Y., et al.[2020]

In a study of 28 patients with high-risk prostate cancer, 50% developed strong immune responses to a vaccine targeting the PSA146-154 peptide, indicating the vaccine's potential to stimulate the immune system against cancer.

Patients who showed enhanced T-cell responses after vaccination had a significantly lower risk of disease progression, and those with specific immune responses tended to have better overall survival rates, averaging 60 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of HLA-A2+ patients with high-risk, hormone-sensitive prostate cancer vaccinated with the prostate specific antigen peptide homologue (PSA146-154). Perambakam, S., Xie, H., Edassery, S., et al.[2021]

In a Phase I clinical trial involving 8 patients with hormone-refractory prostate cancer, a dendritic cell vaccine using a cocktail of prostate cancer-associated peptides was found to be safe, with only minor local skin reactions reported.

One patient achieved a significant reduction in PSA levels (over 50%), while three others had stable or slowed PSA increases, indicating potential efficacy in inducing immune responses against prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial. Fuessel, S., Meye, A., Schmitz, M., et al.[2022]

In a phase I study involving 16 men with hormone refractory prostate cancer, the combination of thalidomide and oral cyclophosphamide was found to be well tolerated, with the most common side effects being mild constipation, peripheral neuropathy, and fatigue.

The treatment showed some efficacy, with 15% of patients experiencing a greater than 50% decrease in prostate-specific antigen (PSA) levels, suggesting potential for further investigation in larger phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalidomide in combination with oral daily cyclophosphamide in patients with pretreated hormone refractory prostate cancer: a phase I clinical trial. Di Lorenzo, G., Autorino, R., De Laurentiis, M., et al.[2020]

Citations

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haldatx.com

haldatx.com/halda-therapeutics-announces-first-in-human-results-for-hld-0915-an-oral-riptac-therapeutic-demonstrating-encouraging-safety-and-anti-tumor-activity-in-metastatic-castration-resistance-prost/

News & - Publications

The first-in-human findings demonstrate that HLD-0915 was well-tolerated and showed encouraging preliminary signs of anti-tumor activity, ...

2.

mdanderson.org

mdanderson.org/newsroom/research-newsroom/new-oral-therapy-shows-early-signs-of-safety-and-effectiveness-i.h00-159780390.html

New oral therapy shows early signs of safety and ...

With that knowledge, researchers are evaluating HLD-0915 in clinical trials to assess its safety and effectiveness in slowing tumor growth.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06800313

NCT06800313 | A Study of HLD-0915 in Patients With ...

Study Overview. Brief Summary. Assessment of the safety and efficacy of HLD-0915 as monotherapy in patients with metastatic castration resistant prostate cancer ...

4.

oncologypipeline.com

oncologypipeline.com/apexonco/triple-meeting-2025-haldas-proximity-play-prostate

Triple meeting 2025 – Halda's proximity play in prostate

HLD-0915's ongoing phase 1 trial has enrolled 31 patients who had progressed on prior systemic therapies. Participants received once daily oral ...

5.

yalemedicine.org

yalemedicine.org/clinical-trials/hld-0915-onc-101-a-study-of-hld-0915-in-patients-with-metastatic-castration-resistant-prostate-canc

Phase 1/2 Study of HLD-0915 in Patients With Metastatic ...

Phase 2 of this study will evaluate the anti-tumor activity of HLD-0915 administered at the RDEs in patients with mCRPC. Phase 2 study design ...

6.

onclive.com

onclive.com/view/fda-grants-fast-track-designation-to-hld-0915-for-metastatic-castration-resistant-prostate-cancer

FDA Grants Fast Track Designation to HLD-0915 for ...

In preclinical prostate cancer models, treatment with HLD-0915 led to tumor shrinkage and reductions in prostate-specific antigen (PSA), with ...

7.

targetedonc.com

targetedonc.com/view/hld-0915-receives-fda-fast-track-designation-for-mcrpc-treatment

HLD-0915 Receives FDA Fast Track Designation for ...

FDA fast-tracks HLD-0915, a novel therapy for metastatic castration-resistant prostate cancer, promising rapid development and potential ...