Clinical trial NCT04662580: ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer
Official title: A Phase 1, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of ARX517 as Monotherapy and in Combination With Androgen Receptor Pathway Inhibitors in Subjects With Metastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Prostate Cancer
Keywords: ADC
Antibody drug conjugate
Prostate neoplasia
Metastatic castration-resistant prostate cancer
PSMA
Prostate specific membrane antigen
PSMA ADC
Prostate Cancer
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-12-10
Enrollment: 253
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study has dose-escalation (Phase 1a) and dose-expansion (Phase 1b) stages to identify the maximum tolerated dose (MTD) and/or recommended development doses (RDDs) of ARX517. The initial treatment regimen is by weight-based infusion at an interval of every 3 weeks. In the Phase 1b dose expansion stage, the Sponsor will evaluate cohorts with alternative dose regimens to determine RDD(s). The term "alternative dose regimen" refers to any monotherapy treatment regimen where ARX517 is not given at a fixed interval of every 3 weeks.

In the Phase 1b dose expansion stage, the Sponsor will also evaluate the safety and preliminary anti-tumor activity of ARX517 in combination with ARPIs (apalutamide or abiraterone acetate plus prednisone). ARPIs will be administered at the approved doses per product information. The starting dose of ARX517 to be given in combination with ARPIs will be determined by data emerging from the monotherapy dose expansion stage.
Primary purpose: TREATMENT

Brief summary: This is a phase 1 study to assess the safety and tolerability of ARX517 as monotherapy or combination therapy in adult subjects with metastatic prostate cancer (mPC).

Detailed description: This is a first-in-human (FIH), Phase 1, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, PK, pharmacodynamic (PDy), and preliminary anti-tumor activity of ARX517 alone, or in combination with androgen receptor pathway inhibitors (ARPIs), in adult subjects with metastatic prostate cancer .

Eligibility criteria: Key Inclusion Criteria:

* Male and ≥18 years at the time of providing written informed consent.
* Histologically confirmed prostate adenocarcinoma.
* For subjects who have not undergone an orchiectomy, must be undergoing treatment with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist and must agree to continue such therapy while on study treatment. Subjects enrolled to mCRPC cohorts must have serum testosterone levels of ≤50ng/dL (1.73nM at Screening).
* Must receive prior treatment(s) as defined in the protocol for each cohort
* Documented evidence of disease progression on or after the most-recent prior regimen for mCRPC cohorts
* mCSPC combination cohorts: High volume metastatic disease documented by CT/MRI and/or 99mTC bone scan (for bone lesions)
* Adequate blood counts
* Must have at least 1 PSMA-positive metastatic lesion and no measurable PSMA-negative lesions by local assessment for alternative dosing regimen and combination cohorts.

Key Exclusion Criteria

* Receipt of chemotherapy within 21 days prior to enrollment; hormonal therapy (not including LHRH analogs) within 7 days prior to enrollment; palliative radiation therapy within 7 days prior to enrollment; or any other anticancer therapy within 21 days prior to enrollment or other therapy for monotherapy cohorts
* Receipt of more than 1 prior taxane regimen or non-taxane chemotherapy for prostate cancer for alternative dose regimen and mCRPC combination cohorts
* Receipt prior apalutamide, enzalutamide, or darolutamide, or AAP for mCRPC combination cohorts
* Receipt any prior chemotherapy or prior ARPI, and must be greater than 90 days of ADT prior to enrollment for mCSPC combination cohorts
* Use of chronic systemic glucocorticoids equivalent to \> 10 mg prednisone daily. Note: short-term administration of systemic corticosteroids \> 10 mg prednisone equivalent (e.g., for allergic reactions or management of immune- or infusion-related AEs) is allowed.
* Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, untreated CNS metastases are eligible provided they have been clinically stable (neurologically stable and not requiring steroids for at least 28 days prior to enrollment).
* History of any invasive malignancy (other than primary) within the previous 2 years prior to the enrollment date that requires active therapy or is at high risk of recurrence in the opinion of the investigator.
* Marked baseline prolongation of QT/QT interval corrected for heart rate (QTc), e.g., a triplicate-average QTc interval \> 480 milliseconds (CTCAE Grade 2) using Fridericia's QT correction formula at any time within 28 days before enrollment, ongoing history of CTCAE Grade ≥2 QTc at enrollment, or anticipated need to perform repeat ECG evaluations to satisfy re-treatment criteria.
* Prior history of interstitial lung disease, pneumonitis, or other clinically significant lung disease within 12 months prior to enrollment date.
* Clinically significant ocular findings by a qualified ophthalmologist or optometrist including active ocular infections or chronic corneal disorders unless approved by the Medical Monitor.
* Peripheral neuropathy Grade ≥ 2 within 28 days prior to enrollment.
* For combination cohorts with apalutamide: no prior history of seizure or condition that may predispose to seizure (including but not limited to prior cerebrovascular accident, TIA or loss of consciousness within the last 12 months, brain AVM, brain metastases).
* 24-hour urine protein \> 1g/24h

Primary outcomes:
measure: Assess incidence of adverse events
timeFrame: 1.5 Years
Secondary outcomes:
measure: Area under the serum concentration-time curve (AUC) for ARX517 alone or in combination with ARPIs
timeFrame: 3 Year
measure: Maximum serum concentration (Cmax) for ARX517 alone or in combination with ARPIs
timeFrame: 3 Year
measure: Trough concentration (Ctrough) for ARX517 alone or in combination with ARPIs
timeFrame: 3 Year
measure: Incidence of ADA against ARX517 alone or in combination with ARPIs
timeFrame: 3 year
measure: Overall survival (OS)
timeFrame: 3 year
measure: Assess changes in serum prostate specific antigen (PSA) levels
timeFrame: 3 year
measure: Progression-free survival (PFS)
timeFrame: 3 year
Other outcomes:
measure: Evaluate of biomarkers
timeFrame: 3 years
measure: Evaluate PSMA expression
timeFrame: 3 years
measure: Assess changes in Brief Pain Inventory-Short Form (BPI-SF)
timeFrame: 3 year
measure: Assess changes in Functional Assessment of Cancer Therapy for Patients with Prostate Cancer (FACIT-P)
timeFrame: 3 year
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles School of Medicine
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center at Mission Bay
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University St. Louis School Medicine Siteman Cancer Center
state: Missouri
city: Omaha
country: United States
facility: GU Research Network
state: Nebraska
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: