Clinical trial NCT06800313: A Study of HLD-0915 in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
Official title: Phase 1/2 Study of HLD-0915 in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer Metastatic Disease
Prostate Cancer (Adenocarcinoma)
Keywords: prostate cancer
RIPTAC
HLD-0915
Lead sponsor: Halda Therapeutics OpCo, Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-30
Enrollment: 33
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Phase 1 dose escalation will employ the BF-BOIN design (to find the Maximum Tolerated Dose (MTD)/ Recommended Dose for Expansion (RDE). BF-BOIN enables backfilling patients to doses that are cleared for safety during the dose escalation, thereby generating additional data on safety, tolerability, and preliminary activity on doses below the MTD. This facilitates the identification of the RDE(s). The BF-BOIN consists of two interrelated components: dose escalation and backfill.
Primary purpose: TREATMENT

Brief summary: Assessment of the safety and efficacy of HLD-0915 as monotherapy in patients with metastatic castration resistant prostate cancer (mCRPC) that have progressed on prior systemic therapies, once a recommended dose for expansion (RDE) has been determined in Phase 1 of the trial.

Detailed description: This is a Phase 1/2, open-label study of the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of oral single-agent HLD-0915. Patients on the study must continue androgen deprivation therapy (ADT) unless surgically castrated,

The study will include an initial Phase 1 portion to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) of HLD-0915 as monotherapy and Phase 2 expansion cohorts to further evaluate the efficacy and safety of HLD-0915.

Phase 1 of this study is an open-label, dose-escalation and cohort expansion study in patients with mCRPC that have progressed after prior systemic therapies. Patients will be enrolled in monotherapy dose-escalation cohorts using a Bayesian optimal interval with backfill (BF-BOIN) design. Patients are treated in cohort size of 3 with the enrollment staggered between cohorts.

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 and patient population will be based on the outcomes of Phase 1 of the trial.

Eligibility criteria: Key Inclusion Criteria:

All patients must meet the following criteria to be eligible for Phase 1 study participation:

1. Males of age 18 years at the time of signing the informed consent form (ICF).
2. Able to understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures.
3. Patients must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
4. Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone.
5. Patients must have progressed on prior line(s) of therapy.
6. Patients must have progressive mCRPC defined as having demonstrated PSA progression on the prior regimen. PSA progression may have occurred with or without accompanying radiographic progression.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
8. Life expectancy of at least 3 months.
9. Adequate hematological, renal, and hepatic function.
10. Able to swallow an oral medication.
11. Willing and able to adhere to the study visit schedule and other protocol requirements.
12. Patients on a stable bisphosphonate or denosumab regimen for 30 days prior to enrollment are eligible.

Key Exclusion Criteria:

Patients with any of the following will be excluded from participation in Phase 1 of the study:

1. Has experienced a recent major bleed or has a known bleeding disorder.
2. Tumors exhibiting neuroendocrine or small cell carcinoma component by histopathology.
3. Receiving continuous corticosteroids at prednisone-equivalent dose of \>10 mg/day.
4. Has received systemic anti-cancer therapy (cytotoxic chemotherapy, biologic agent, checkpoint inhibitors, or radiation therapy) or investigational drugs within 2 weeks prior to first dose of study drug with certain exceptions requiring longer washout periods.
5. History of myocardial infarction or unstable angina within 6 months prior to enrollment, or clinically significant cardiac disease.
6. Known clinically significant active or chronic infection.
7. Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease.

Primary outcomes:
measure: Phase 1: Frequency of dose-limiting toxicities (DLTs)
timeFrame: 21 days
measure: Phase 1: Frequency and severity of AEs and serious adverse events (SAEs), including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs changed from baseline
timeFrame: 21 days
Secondary outcomes:
measure: Phase 1: Plasma concentrations of HLD-0915 as a function of time post-dosing
timeFrame: 21 days
measure: Phase 1: Plasma PK Parameters (Cmax)
timeFrame: 21 days
measure: Phase 1: Plasma PK Parameters (Tmax)
timeFrame: 21 days
measure: Phase 1: Plasma PK Parameters (T1/2)
timeFrame: 21 days
measure: Phase 1: Plasma PK Parameters (AUC0-inf)
timeFrame: 21 days
measure: Phase 1: The proportion of pts with a confirmed prostate-specific antigen (PSA) decline ≥30%, ≥50%, and ≥90%
timeFrame: 21 days
measure: Phase 1: Objective response rate (ORR) per RECIST in evaluable patients
timeFrame: 21 days
measure: Phase 1: Duration of response (DOR)
timeFrame: 21 days
measure: Phase 1: Radiographic progression-free survival (rPFS)
timeFrame: 21 days
measure: Phase 1: Time to response (TTR)
timeFrame: 21 days
measure: Phase 1: Change in PSA over time
timeFrame: 21 days
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Grand Rapids
country: United States
facility: START Midwest, LLC
state: Michigan
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Austin
country: United States
facility: NEXT Austin
state: Texas
Study officials:
References: