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Advanced Prostate CancerPhase 1/2NCT03577028

Study of HPN424 in Patients With Advanced Prostate Cancer

A Phase 1/2 study testing HPN424 Fixed IV 1.3 to 150 ng/kg, HPN424 Prime Step IV 36 ng/kg Target and HPN424 1 Prime Step IV 225-300 ng/kg Target in people with Advanced Prostate Cancer, run by Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 15 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

An open-label, Phase 1/2a, study of HPN424 as monotherapy to assess the safety, tolerability and PK in patients with advanced prostate cancer refractory to androgen therapy Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Advanced Prostate Cancer
What is being tested?
HPN424 Fixed IV 1.3 to 150 ng/kg, HPN424 Prime Step IV 36 ng/kg Target and HPN424 1 Prime Step IV 225-300 ng/kg Target
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
15 sitesin 2 countries
Study dates
24 Jul 2018to 27 Feb 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male patients ≥18 years of age at the time of signing informed consent
  • Histologically or cytologically confirmed adenocarcinoma of the prostate
  • Progressive metastatic castrate-resistant prostate cancer (mCRPC):
  • Serum testosterone levels less than 50 ng/dL (or ≤0.50 ng/mL or 1.73 nmol/L) within 28 days prior to start of study drug
  • Radiographic evidence of metastatic disease
  • Disease progression on the prior systemic regimen, per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria:
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  • A sequence of at least 2 rising PSA values measured at a minimum of 1 week apart with a 2 ng/mL minimum starting value, or ii. Appearance of two or more new lesions on bone scans, or iii. Progressive visceral disease, or iv. Progressive nodal disease; previously normal (<1.0 cm) lymph nodes must have grown by ≥5 mm in the short axis from baseline or nadir and be ≥1.0 cm in the short axis to be considered to have progressed
  • Must have received at least 2 prior systemic therapies approved for mCRPC
  • Ongoing androgen depletion therapy with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration)
  • For patients previously treated with first generation anti-androgens, discontinuation must have occurred ≥4 weeks (for flutamide or nilutamide) or ≥6 weeks (for bicalutamide) prior to start of study drug, with no evidence of an anti-androgen withdrawal response (i.e., no decline in serum PSA)
  • For patients previously treated with a second-generation anti-androgen (e.g., enzalutamide or equivalent) or with abiraterone acetate, discontinuation must have occurred 2 weeks or 5 half-lives prior to start of study drug
  • For patients previously treated with systemic chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent, discontinuation must have occurred ≥2 weeks, or at least 4 half-lives (up to 4 weeks), whichever is longer, prior to start of study drug
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate bone marrow function, including:
  • Absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5 x 109/L
  • Platelets ≥100,000/mm3 or ≥100 x 109/L
  • Hemoglobin ≥9 g/dL (no transfusions allowed within 1 week prior to screening)
  • Adequate renal function, including:
  • Estimated creatinine clearance ≥50 mL/min as calculated using the method standard for the institution
  • Adequate liver function, including:
  • Total serum bilirubin ≤1.5 x upper limit of normal (ULN) unless the patient has documented Gilbert syndrome in which case the maximum total serum bilirubin should be 5 mg/dL
  • Aspartate and Alanine transaminase (AST and ALT) ≤2.5 x ULN
  • Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 except for adverse events (AEs) not constituting a safety risk per the Investigator
  • If of reproductive potential, willing to use 1 effective method of contraception (as defined in this protocol) during the treatment period, if partner is a female of childbearing potential
  • Willing to complete all scheduled visits and assessments at the institution administering therapy
  • Able to read, understand and provide written informed consent

Who cannot join

  • Previously treated or current brain metastases
  • Untreated spinal cord compression. Participants must be neurologically stable off steroids for at least 4 weeks prior to first dose of study drug
  • Ongoing treatment with anti-tumor necrosis factor (TNF) alpha therapies, systemic corticosteroids (prednisone dose >10 mg per day or equivalent), or other immune suppressive drugs
  • History of or known or suspected autoimmune disease (exception(s): patients with vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at Screening are allowed)
  • History of clinically significant cardiovascular disease such as symptomatic congestive heart failure (CHF), uncontrolled hypertension defined as sustained BP >150 mmHg systolic, or >100 mmHg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening), unstable angina pectoris, clinically significant cardiac arrhythmias, history of stroke (including TIA, or other ischemic event) within 6 months before first dose of study drug, myocardial infarction within 6 months before first dose of study drug, history of thromboembolic event within 3 months before first dose of study drug
  • Known active or chronic hepatitis B or hepatitis C as demonstrated by hepatitis B surface antigen (HBsAg) positivity and/or anti-hepatitis C virus (HCV) positivity, respectively, or known history of human immunodeficiency virus (HIV) seropositive status
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  • Clinically active liver disease, including liver cirrhosis of Child-Pugh class B or C
  • Second primary malignancy that has not been in remission for greater than 3 years. Exceptions that do not require a 3-year remission: non-melanoma skin cancer, resected melanoma in situ, or non-muscle invasive urothelial carcinoma
  • In the judgment of the Investigator, patient has a clinically significant concurrent illness or psychological, familial, sociological, geographical, or other concomitant condition that would not permit adequate follow-up and compliance with the study protocol
  • Any serious underlying medical or psychiatric condition (e.g., alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the patient to understand informed consent or that in the opinion of the Investigator would contraindicate the patient's participation in the study or confound the results of the study
  • Known hypersensitivity, allergies, or intolerance to immunoglobulins, or to any excipient contained in HPN424 (see Investigator's Brochure)
  • Is a participant or plans to participate in another interventional clinical study, while taking part in this protocol. Participation in an observational study is acceptable

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States14 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago

    Chicago, Illinois, 60637

  • Mary Crowley Cancer Research

    Dallas, Texas, 75230

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53972

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • New York Presbyterian Hospital-Columbia University Medical Center.

    New York, New York, 10032

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2497

  • Oregon Health & Science University Knight Cancer Institute

    Portland, Oregon, 97239

  • University of California San Francisco

    San Francisco, California, 94143

Other trials in United States

United Kingdom1 site

  • The Royal Marsden Hospital

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

Official title: A Phase 1/2a Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN424 in Patients With Advanced Prostate Cancer Refractory to Androgen Therapy

An open-label, Phase 1/2a, study of HPN424 as monotherapy to assess the safety, tolerability and PK in patients with advanced prostate cancer refractory to androgen therapy

Being tested
HPN424 Fixed IV 1.3 to 150 ng/kg, HPN424 Prime Step IV 36 ng/kg Target, HPN424 1 Prime Step IV 225-300 ng/kg Target, HPN424 2 Prime Step IV 300 ng/kg Target, HPN424 2 Prime Step IV 450 ng/kg Target
Keywords
Prostate Cancer, Metastatic Castration Resistant Prostate Cancer, Harpoon, TriTAC
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HPN424 Fixed IV 1.3 to 150 ng/kgBiological

    Fixed dose IV cohorts at doses from 1.3 to 150 ng/kg

  • HPN424 Prime Step IV 36 ng/kg TargetBiological

    Step-dosing IV cohort at a single Prime Dose followed by the Target Dose (12/36 ng/kg)

  • HPN424 1 Prime Step IV 225-300 ng/kg TargetBiological

    Step-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (100/300 ng/kg and 75/225 ng/kg)

  • HPN424 2 Prime Step IV 300 ng/kg TargetBiological

    Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (50/150/300 ng/kg with prior chemotherapy and 50/150/300 ng/kg no prior chemotherapy)

  • HPN424 2 Prime Step IV 450 ng/kg TargetBiological

    Step-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (100/300/450 ng/kg and 50/150/450 ng/kg)

  • HPN424 Fixed SCBiological

    Fixed subcutaneous dose 120 ng/kg

Study groups in NCT03577028
Study groupRoleWhat they receive
Fixed IVExperimentalHPN424 administered once weekly via IV infusion in doses ranging from 1.3 to 150 ng/kg
Receives: Biological: HPN424 Fixed IV 1.3 to 150 ng/kg
1 Prime Step IV 36 ng/kg TargetExperimentalStep-dosing IV cohort who received a single Prime Dose followed by the Target Dose (12/36 ng/kg)
Receives: Biological: HPN424 Prime Step IV 36 ng/kg Target
1 Prime Step IV 225-300 ng/kg TargetExperimentalStep-dosing IV cohorts who received a single Prime Dose followed by the Target Dose (100/300 ng/kg and 75/225 ng/kg]
Receives: Biological: HPN424 1 Prime Step IV 225-300 ng/kg Target
2 Prime Step IV 300 ng/kg TargetExperimentalStep-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (50/150/300 ng/kg with prior chemotherapy and 50/150/300 ng/kg no prior chemotherapy)
Receives: Biological: HPN424 2 Prime Step IV 300 ng/kg Target
2 Prime Step IV 450 ng/kg TargetExperimentalStep-dosing IV cohorts who received 2 Prime Doses followed by the Target Dose (100/300/450 ng/kg and 50/150/450 ng/kg)
Receives: Biological: HPN424 2 Prime Step IV 450 ng/kg Target
Fixed SCExperimentalFixed subcutaneous dose (120 ng/kg)
Receives: Biological: HPN424 Fixed SC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number and Severity of Dose Limiting Toxicities (DLTs) Following Treatment With Escalating Doses of HPN424

    Assess safety and tolerability at increasing dose levels of HPN424 in successive cohorts of patients with metastatic castrate resistant prostate cancer (mCRPC) to estimate the maximum tolerated dose (MTD). The study was terminated early, therefore the primary goal of the final data analysis was to look at dosing schedule rather than individual dose levels. The results displayed are shown broken out by dosing schedules and no analysis of specific dose levels was performed. This analysis is as outlined in the final Statistical Analysis Plan.

    Measured: 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2018
  2. Study start24 Jul 2018
  3. Primary completion27 Feb 2023
  4. Study completion27 Feb 2023

Why it stopped: Decision not to continue to the expansion portion of the study

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03577028
Sponsor's protocol ID
HPN424-1001
Status last verified
Jan 2024
First submitted
22 Jun 2018
Last updated
14 Feb 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing HPN424 Fixed IV 1.3 to 150 ng/kg, HPN424 Prime Step IV 36 ng/kg Target and HPN424 1 Prime Step IV 225-300 ng/kg Target in people with Advanced Prostate Cancer, run by Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number and Severity of Dose Limiting Toxicities (DLTs) Following Treatment With Escalating Doses of HPN424 (time frame: 21 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03577028.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2024.

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