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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03577028
Other study ID # HPN424-1001
Secondary ID
Status Terminated
Phase Phase 1/Phase 2
First received
Last updated
Start date July 24, 2018
Est. completion date February 27, 2023

Study information

Verified date January 2024
Source Harpoon Therapeutics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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


Recruitment information / eligibility

Status Terminated
Enrollment 104
Est. completion date February 27, 2023
Est. primary completion date February 27, 2023
Accepts healthy volunteers No
Gender Male
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Male patients =18 years of age at the time of signing informed consent 2. Histologically or cytologically confirmed adenocarcinoma of the prostate 3. Progressive metastatic castrate-resistant prostate cancer (mCRPC): 1. 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 2. Radiographic evidence of metastatic disease 3. Disease progression on the prior systemic regimen, per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria: i. 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 4. Must have received at least 2 prior systemic therapies approved for mCRPC 5. Ongoing androgen depletion therapy with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration) 6. 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) 7. 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 8. 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 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 10. Adequate bone marrow function, including: 1. Absolute neutrophil count (ANC) =1500/mm3 or =1.5 x 109/L 2. Platelets =100,000/mm3 or =100 x 109/L 3. Hemoglobin =9 g/dL (no transfusions allowed within 1 week prior to screening) 11. Adequate renal function, including: a. Estimated creatinine clearance =50 mL/min as calculated using the method standard for the institution 12. Adequate liver function, including: 1. 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 2. Aspartate and Alanine transaminase (AST and ALT) =2.5 x ULN 13. 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 14. 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 15. Willing to complete all scheduled visits and assessments at the institution administering therapy 16. Able to read, understand and provide written informed consent Exclusion Criteria: 1. Previously treated or current brain metastases 2. Untreated spinal cord compression. Participants must be neurologically stable off steroids for at least 4 weeks prior to first dose of study drug 3. 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 4. 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) 5. 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 6. 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 7. Clinically active liver disease, including liver cirrhosis of Child-Pugh class B or C 8. 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 9. 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 10. 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 11. Known hypersensitivity, allergies, or intolerance to immunoglobulins, or to any excipient contained in HPN424 (see Investigator's Brochure) 12. 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

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
HPN424 Fixed IV 1.3 to 150 ng/kg
Fixed dose IV cohorts at doses from 1.3 to 150 ng/kg
HPN424 Prime Step IV 36 ng/kg Target
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 Target
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 Target
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 Target
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 SC
Fixed subcutaneous dose 120 ng/kg

Locations

Country Name City State
United Kingdom The Royal Marsden Hospital Sutton Surrey
United States University of Colorado Hospital Aurora Colorado
United States Massachusetts General Hospital Boston Massachusetts
United States Northwestern University Chicago Illinois
United States University of Chicago Chicago Illinois
United States Mary Crowley Cancer Research Dallas Texas
United States UT Southwestern Medical Center Dallas Texas
United States Karmanos Cancer Institute Detroit Michigan
United States USC Norris Comprehensive Cancer Center Los Angeles California
United States University of Wisconsin Carbone Cancer Center Madison Wisconsin
United States Sarah Cannon Research Institute Nashville Tennessee
United States New York Presbyterian Hospital-Columbia University Medical Center. New York New York
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States Oregon Health & Science University Knight Cancer Institute Portland Oregon
United States University of California San Francisco San Francisco California

Sponsors (1)

Lead Sponsor Collaborator
Harpoon Therapeutics

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 21 days
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