A Phase 1b/2 Study of BXCL701, Administered in Combination with Pembrolizumab (PEMBRO; Keytruda®) in Patients with Small Cell Neuroendocrine Prostate Cancer (SCNC; NEPC)
- Conditions
- Small Cell Neuroendocrine Prostate CancerMedDRA version: 20.0Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003734-32-GB
- Lead Sponsor
- BioXcel Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 68
1. Patient has evidence of progressive mCRPC as defined by PCWG3 criteria.
2. Progression during or following completion of at least 1 prior line of systemic therapy for locally advanced or metastatic prostate cancer.
a. Patients with de novo small cell prostate cancer are not required to have received androgen deprivation therapy (ADT).
3. Efficacy Stage only:
For Cohort A (SCNC):
a. Patient has histologic evidence of SCNC either with archival tissue or a fresh tumor biopsy obtained during Screening. Archival or fresh tumor biopsy tissue must be submitted for a central laboratory pathology review; however, enrollment can proceed if SCNC is determined by a local pathology review. (Central pathology review is optional for patients enrolled in the lead-in.)
b. Patient has previously received at least 1 prior line of cytotoxic chemotherapy. Patients who either have refused chemotherapy or are considered unsuitable for chemotherapy may be eligible following discussion with the sponsor.
c. Must be willing to undergo metastatic tumor biopsy during Screening. Requirement may be waived in patients without safely accessible lesion or for patients with evaluable archival metastatic tumor tissue.
d. Has measurable disease per RECIST 1.1 criteria.
For Cohort B (Adenocarcinoma):
a. Patient has histologically or cytologically confirmed adenocarcinoma of the prostate without small cell neuroendocrine features.
b. Patients with soft tissue disease must provide a fresh core or excisional biopsy or archival tissue obtained = 3mo prior to study start from a site not previously irradiated for central pathology review; however enrollment may proceed if predominant adenocarcinoma without small cell neuroendocrine features is determined by local pathology review.
c. Has been treated with at least 1 but no more than 2 second generation AR pathway target agents (e.g., abiraterone acetate and/or enzalutamide or other next generation agent) and at least 1 regimen/line of taxane containing chemotherapy in the metastatic castration-sensitive prostate cancer (mCSPC) or mCRPC setting. Patients with known actionable mutations should have progressed applicable standard care targeted therapy or have documented intolerance to or be unsuitable for such therapy.
d. RECIST 1.1 measurable disease or detectable bone metastases by whole body bone scintigraphy.
4. Patient has serum testosterone <50 ng/dL during Screening except for those with de novo small cell prostate cancer.
a. Patients with treatment-emergent SCNC without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analog during the course of protocol therapy except for patients with de novo small cell prostate cancer.
5. Patient has an ECOG performance status of 0-2.
6. Patient is =18 years of age.
7. Patient’s acute toxic effects of previous anticancer therapy have resolved to =Grade 1 except for Grade 2-3 peripheral neuropathy or any grade of alopecia.
8. Patient has adequate baseline organ function, as demonstrated by the following:
a. Serum creatinine (Cr) =1.5 times institutional upper limit of normal (ULN) or calculated Cr clearance >50 mL/min.
b. Serum albumin =2.5 g/dL.
c. Total bilirubin =1.5 × ULN.
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × institutional ULN (patients with hepatic metastases must have AST/ALT =5 × ULN).
9. Patient has adequate baseline hematologic function, as demonstrated by the following:
a. Abso
1. Patient has received treatment with >2 cytotoxic chemotherapy regimens for castration-resistant prostate cancer (CRPC). Chemotherapy in the hormone-sensitive setting does not count in this assessment provided the last dose was >6 months before study entry. A change in chemotherapy agents due to intolerance after brief exposure may not count in this assessment, pending review with Medical Monitor.
2. Patient has received external-beam radiation or another systemic anticancer therapy within 14 days or 5 half-lives, whichever is shorter, prior to study treatment.
3. Patient has received treatment with an investigational systemic anticancer agent within 14 days prior to study drug administration.
4. Patient has received prior treatment with an anti-PD-1, anti-PD-L1, anti-programmed death ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., cytotoxic T lymphocyte–associated antigen 4 [CTLA-4], OX-40, CD137), or requires concomitant treatment with DPP4 inhibitors (e.g., gliptins).
5. Patient has an additional active malignancy that may confound the assessment of the study endpoints. If the patient has a past cancer history (active malignancy within 2 years prior to study entry) with substantial potential for recurrence, this must be discussed with the sponsor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer and carcinomas in situ (including transitional cell carcinoma, anal carcinoma, and melanoma in situ).
6. Patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
7. Patient has QT interval corrected for heart rate using Bazett’s formula (QTcB) >480 msec at Screening.
8. Patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the investigator would put the patient at significant risk for pulmonary complications during the study.
9. Patient has brain or leptomeningeal metastases that are symptomatic and progressive on imaging. Patients with a history of CNS metastases must have received appropriate treatment. CNS imaging is not required prior to study entry unless there is a history of CNS involvement or clinical suspicion of CNS involvement. Imaging of patients with a prior history of CNS metastases should be compared to prior imaging to discern disease progression.
10. Patient has an active autoimmune disease or Grade =3 (non-infectious) pneumonitis that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) or treatment with drugs (e.g., neomercazol, carbimazole, etc.) that function to decrease the generation of thyroid hormone by a hyperfunctioning thyroid gland (e.g., in Graves’ disease) is not considered a form of systemic treatment of an autoimmune disease.
11. Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a prednisone equivalent dose of >10 mg daily fo
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method