An Open-label, Multicenter, Phase 1b Study of JNJ-63723283, a PD-1 Inhibitor, Administered in Combination with Apalutamide in Subjects with Metastatic Castration- Resistant Prostate Cancer
- Conditions
- Metastatic Castration-Resistant Prostate Cancer10036958
- Registration Number
- NL-OMON50489
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
Each potential subject must satisfy all of the following criteria to be
enrolled in the study:
1. >=18 years of age
2. Criterion modified per Amendment 3
2.1
* Pathologically confirmed adenocarcinoma of the prostate on initial diagnosis
* Pathologically confirmed t-SCNC (by screening biopsy of a metastatic site):
Cohort 5 only
3. Criterion modified per Amendment 1
3.1 Metastatic disease as documented by technetium-99m (99mTc) bone scan or
metastatic lesions by computed tomography (CT) or magnetic resonance imaging
(MRI) scans (visceral or lymph node disease). CT-portion of PET/CT scan may be
used for eligibility. If lymph node metastasis is the only evidence of
metastatic disease, it must be >= 1.0 cm in the short axis and above the level
of the iliac bifurcation.
4. Criterion modified per Amendment 1
4.1 Criterion modified per Amendment 4
4.2 Criterion modified per Amendment 5
4.3 Progression (all of the criteria below must be met):
* PSA progression confirmed per Prostate Cancer Clinical Trials Working Group
(PCWG3): Castration-resistant prostate cancer (CRPC) demonstrated during
continuous ADT, defined as 2 rises of PSA, at least 1 week apart with the last
PSA >=2 ng/mL.
* PSA progression on AR-targeted therapy (abiraterone plus
prednisone/prednisolone [AA-P]; apalutamide, darolutamide, or enzalutamide).
* Radiographic progression of soft tissues according to Response Evaluation
Criteria in Solid Tumors, version 1.1 (RECIST 1.1) modified based on PCWG3, or
radiographic progression of bone according to PCWG3.
5. Criterion modified per Amendment 2
5.1 Criterion modified per Amendment 3
5.2 Criterion modified per Amendment 4
5.3 Criterion modified per Amendment 5
5.4 Progressed while on therapy with AA-P, enzalutamide, darolutamide, or
apalutamide. No washout is required, and no additional therapy may have been
administered between discontinuation of AR-targeted the agents and study
treatment. Subjects will be assigned to cohorts based on the results of the
biomarker panel.
Cohort 1: Biomarker-negative or biomarker-unknown subjects with adenocarcinoma
(and not t-SCNC) who progressed on AA-P
Cohort 2: Biomarker-negative or biomarker-unknown subjects with adenocarcinoma
(and not t-SCNC) who progressed on apalutamide, darolutamide, or enzalutamide
Cohort 3: Biomarker-positive subjects who progressed on AA-P
Cohort 4: Biomarker-positive subjects who progressed on apalutamide,
darolutamide, or enzalutamide
Cohort 5: Biomarker-negative subjects with t-SCNC who progressed on treatment
with AA-P, apalutamide, darolutamide, or enzalutamide
Note: Prior docetaxel for HSPC is allowed; no washout is required.
Note: Subjects who have developed t-SCNC and are biomarker-positive will be
assigned to either Cohort 3 or 4, depending on therapy history.
6. Surgical or medical castration, with testosterone levels of <50 ng/dL. If
the subject is being treated with GnRH analogs (subject who has not undergone
bilateral orchiectomy), this therapy must have been initiated at least 4 weeks
prior to first dose of study drug and must be continued throughout the study.
7. ECOG PS grade of 0 or 1 (see Attachment 2 for conversion from KPS)
8. Criterion modified per Amendment 3
8.1 Criterion modified per Amendment 4
8.2 Clinical laboratory values at Screening:
a. Hemoglobi
1. Criterion modified per Amendment 3
1.1 Initial diagnosis of primary prostatic neuroendocrine or small cell
carcinoma.
2. Brain metastases.
3. Prior treatment with an anti-PD-1, anti-PD-L1, or anti CTLA-4 antibody.
4. Prior chemotherapy, except for docetaxel for HSPC.
5. Prior therapy with poly ADP-ribose polymerase (PARP) inhibitors.
6. Criterion modified per Amendment 5
6.1 Both prior abiraterone acetate plus prednisone/prednisolone (AA-P) and
apalutamide, darotulamide or enzalutamide.
7. Criterion modified per Amendment 3
7.1 Therapies that must be discontinued or substituted at least 4 weeks prior
to first dose of
study drug include the following:
* Medications known to lower the seizure threshold (see Prohibited Medications)
* Herbal and non-herbal products that may decrease PSA levels (eg, megestrol,
5a-
reductase inhibitors).
8. Criterion modified per Amendment 3
8.1 Any investigational agent for the treatment of castration-resistant
prostate cancer
9. If a subject has undergone major surgery, they must have recovered
adequately from the toxicities or complications from the intervention within 4
weeks prior to starting therapy.
10.History of any of the following:
* Seizure or known condition that may pre-dispose to seizure (including but not
limited
to: stroke, transient ischemic attack, or loss of consciousness within 1 year
prior to first
dose of study drug, brain arteriovenous malformation; or intracranial masses
such as
schwannomas and meningiomas that are causing edema or mass effect)
* Active malignancies (ie, requiring treatment change in the last 24 months)
other than
urothelial cancer (except skin cancers within the last 24 months that are
considered
completely cured).
* Any of the following within 6 months prior to first dose of study drug:
Severe or
unstable angina, myocardial infarction, symptomatic congestive heart failure,
arterial or
venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident
including transient ischemic attacks), or clinically significant ventricular
arrhythmias or
New York Heart Association (NYHA) Class II to IV heart disease; uncomplicated
deep
vein thrombosis (DVT) is not considered exclusionary
11. Criterion modified per Amendment 3
11.1 Criterion modified per Amendment 4
11.2 Uncontrolled hypertension (2 or more readings of blood pressure at the
clinic that are
above: systolic >=160 mmHg or diastolic >=100 mmHg)
12. Gastrointestinal disorder affecting absorption.
13. Active infection or conditions requiring treatment with antibiotics.
14. Has taken immunosuppressive doses of systemic medications, such as
corticosteroids (doses >10 mg/day prednisone or equivalent), within 2 weeks
before first dose of study drug.
15. Active autoimmune disease or a documented history of autoimmune disease
that requires immunosuppressive medications (eg, chronic steroids,
methotrexate, tacrolimus, etc.).
Note: Subjects with vitiligo or resolved childhood asthma/atopy would be an
exception to this rule. Subjects that require intermittent use of
bronchodilators or local steroid injections would not be excluded from the
study. Subjects with a history of transient autoimmune manifestations of an
acute infectious disease that resolved upon treatment of the infectious agent
(eg,
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p># Incidence and severity of adverse events.<br /><br># PSA response rate at 12 weeks in all-treated subjects.</p><br>
- Secondary Outcome Measures
Name Time Method <p># Maximal PSA decline in all-treated subjects.<br /><br># Circulating tumor cell (CTC) response.</p><br>