Prostatic Neoplasms, Adenocarcinoma
Conditions
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.
Interventions
DRUGJNJ-69086420
Participants will receive JNJ-69086420.
DRUGJNJ-78278343
Participants will receive JNJ-78278343.
RADIATIONStereotactic body radiation therapy
Participants will receive stereotactic body radiaition therapy.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | Up to 2 years and 4 months | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. |
| Part 1: Number of Participants with Dose-Limiting Toxicity (DLT) | Up to 2 years and 4 months | Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. |
| Number of Participants with AEs by Severity | Up to 2 years and 4 months | Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Prostate Specific Antigen (PSA) Response | Up to 2 years and 4 months | PSA response rate is defined as the percentage of participants with a decline of PSA of 50 percent (%) or more from baseline and that is subsequently confirmed. |
| Overall Response Rate (ORR) | Up to 2 years and 4 months | ORR is defined as the percentage of participants who have a Partial Response (PR) or better according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 without evidence of bone progression according to Prostate Cancer Working Group 3 (PCWG3). |
| Maximum Observed Serum Concentration/Radioactivity (Cmax) of JNJ-69086420 | Up to 2 years and 4 months | Cmax is defined as the maximum observed serum concentration/radioactivity of JNJ-69086420. |
| Time to Reach Maximum Observed Serum Concentration/Radioactivity (Tmax) of JNJ-69086420 | Up to 2 years and 4 months | Tmax is defined as time to reach maximum observed serum concentration/radioactivity of JNJ-69086420. |
| Area Under the Serum Concentration-time Curve From Time Zero to t Time (AUC[0-t]) of JNJ-69086420 | Up to 2 years and 4 months | AUC(0-t) is defined as the area under the serum concentration-time curve from time zero to t of JNJ-69086420. |
| Number of Participants With Anti-JNJ-69086420 Antibodies | Up to 2 years and 4 months | Number of participants with anti-JNJ-69086420 antibodies will be assessed to evaluate the potential immunogenicity. |
| Part 3: Serum Concentration of JNJ-78278343 | Up to 2 years and 4 months | Venous blood samples will be collected for assessment of serum concentrations of JNJ-78278343. |
| Part 3:Number of Participants With Anti-JNJ-78278343 Antibodies | Up to 2 years and 4 months | Number of participants with anti-JNJ-78278343 antibodies will be assessed to evaluate the potential immunogenicity. |
Countries
United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed