Clinical trial NCT04644770: A Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer
Official title: A Phase 1 Study of JNJ-69086420, an Actinium-225-Labeled Antibody Targeting Human Kallikrein-2 (hK2) for Advanced Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Prostatic Neoplasms
Adenocarcinoma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-11-25
Enrollment: 247
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the recommended Phase 2 dose(s) (RP2D\[s\]) of JNJ-69086420 in Part 1 (Dose Escalation), to determine safety and preliminary signs of clinical activity at the RP2D(s) in Part 2 (Dose Expansion), to determine safety of JNJ-69086420 at the RP2D(s) as a combination therapy in Part 3 (combination therapy) and to determine safety of JNJ-69086420 at the RP2D(s) in participants with metastatic hormone-sensitive prostate cancer (mHSPC) in Part 4.


Eligibility criteria: Inclusion Criteria:

* For Part 1, Part 2, Part 3: Metastatic castration resistant prostate cancer (mCRPC) with histologic confirmation of adenocarcinoma (adenocarcinoma with small-cell or neuroendocrine features is allowed) with prior exposure to at least one androgen receptor (AR) targeted therapy (for example \[e.g.\], abiraterone acetate, enzalutamide, apalutamide, darolutamide). In addition: Part 1: prior taxane or other chemotherapy is acceptable but not required. Part 2a: prior taxane or other chemotherapy required, Part 2b: no prior taxane or other chemotherapy, Part 2c: mCRPC that has progressed after prior treatment with lutetium Lu-177 vipivotide tetraxetan, with or without prior chemotherapy, Part 3: prior taxane or other chemotherapy is acceptable but not required \& For Part 4a: metastatic HSPC, For Part 4b: disease that can be treated with less than or equal to (\<=) 5 radiation fields and no visceral metastases
* Parts 1, 2 \& 3: Prior orchiectomy or medical castration, or, for participants who have not undergone orchiectomy, must be receiving ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analog (agonist or antagonist) prior to the first dose of study drug and must continue this therapy throughout the treatment phase. This criterion does not apply to Part 4
* Palliative radiotherapy (e.g. soft tissue lesions) must be completed greater than (\>) 2 weeks prior to start of study drug except for palliative radiotherapy for pain (e.g., bone pain), which may be used any time prior to first dose
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate organ functions as reflected in laboratory parameters

Exclusion Criteria:

* Prior treatment with radium Xofigo (Ra 223 dichloride), strontium, samarium, or other radioconjugate therapy, other systemic anti-neoplastic therapy \<=30 days prior to the first dose of study drug except for luteinizing hormone-releasing hormone agonists/antagonists or GnRH agonists/antagonists. Novel androgen axis drugs \<=14 days prior to the first dose of study drug. In addition: Part 2b: Must not have received prior treatment with chemotherapy (eg, docetaxel) or poly ADP ribose polymerase (PARP) inhibitors, Part 2c: Prior treatment with lutetium Lu-177 vipivotide tetraxetan is required, but must have been completed \>42 days prior to first dose of study drug, Part 3: Must not have received prior treatment with JNJ-78278343, Part 4: Must not have received ADT or AR-targeted therapy less than or equal to (\<=) 56 days prior to first dose of study drug
* Known history of myelodysplastic syndrome, leukemia, or hematological malignancy with features suggestive of myelodysplastic syndrome/acute myeloid leukemia at any timepoint
* Toxicity from prior anticancer therapy has not resolved to baseline levels or to Grade \<= 1 (except alopecia, radiation tissue fibrosis, or peripheral neuropathy)
* Known allergies, hypersensitivity, or intolerance to JNJ-69086420 or its excipients and protein therapeutics. For Part 3, known allergies, hypersensitivity, or intolerance to JNJ-78278343 or its excipients or protein therapeutics
* Active or chronic hepatitis B or hepatitis C infection

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 2 years and 4 months
measure: Part 1: Number of Participants with Dose-Limiting Toxicity (DLT)
timeFrame: Up to 2 years and 4 months
measure: Number of Participants with AEs by Severity
timeFrame: Up to 2 years and 4 months
Secondary outcomes:
measure: Percentage of Participants with Prostate Specific Antigen (PSA) Response
timeFrame: Up to 2 years and 4 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 2 years and 4 months
measure: Maximum Observed Serum Concentration/Radioactivity (Cmax) of JNJ-69086420
timeFrame: Up to 2 years and 4 months
measure: Time to Reach Maximum Observed Serum Concentration/Radioactivity (Tmax) of JNJ-69086420
timeFrame: Up to 2 years and 4 months
measure: Area Under the Serum Concentration-time Curve From Time Zero to t Time (AUC[0-t]) of JNJ-69086420
timeFrame: Up to 2 years and 4 months
measure: Number of Participants With Anti-JNJ-69086420 Antibodies
timeFrame: Up to 2 years and 4 months
measure: Part 3: Serum Concentration of JNJ-78278343
timeFrame: Up to 2 years and 4 months
measure: Part 3:Number of Participants With Anti-JNJ-78278343 Antibodies
timeFrame: Up to 2 years and 4 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Metairie
country: United States
facility: East Jefferson General Hospital
state: Louisiana
city: Omaha
country: United States
facility: XCancer Omaha / Urology Cancer Center
state: Nebraska
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: