A Trial of BXCL701 and Pembrolizumab in Patients With mCRPC Either Small Cell Neuroendocrine Prostate Cancer or Adenocarcinoma Phenotype.

NCT03910660 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BXCL701-201
• Study Type: interventional
• Target: 98
• Locations: 2 countries
• Sites: 12

Brief Summary

An open-label, multicenter, Phase 1b/2 study to identify the recommended Phase 2 dose and assess the efficacy and safety of BXCL701 administered orally, as monotherapy and in combination with PEMBRO, in patients with mCRPC. Patients enrolled in the Phase 2a portion of the study will have either Small Cell Neuroendocrine Prostate Cancer(SCNC)(Cohort A) or adenocarcinoma phenotype (Cohort B), while the Phase 2b randomized portion of the study will enroll only the histologic subtype(s) showing preliminary evidence in Phase 2a. The study will also assess other efficacy parameters, such as rPFS, PSA PFS, OS, and DOR, as well as the safety of the combined treatment. The study will consist of three components.

Conditions

Prostate Cancer; Neuroendocrine Tumors; Small Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Phase 2a: Estimate the composite response rate of the combination of BXCL701 + PEMBRO

  Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria; circulating tumor cell (CTC) conversion from \>5/7.5 mL to \<5/7.5 mL per Veridex assay; and 50% or greater prostate-specific antigen (PSA) decline from baseline.

  up to 36 months

• Phase 2b: Evaluate response rates in patients treated with the combination of BXCL701 + PEMBRO and with BXCL701 monotherapy

  To evaluate the response rates, defined by RECIST 1.1 criteria, by histologic subtype in patients treated with the combination of BXCL701 + PEMBRO and with BXCL701 monotherapy.

  up to 36 months

Secondary Outcomes (8)

• Phase 2a: Estimate the median radiographic progression-free survival (rPFS) of the combination of BXCL701 and PEMBRO in Cohort A and B

  up to 36 months

• Phase 2a: Estimate the median PSA progression-free survival (PSA PFS) of the combination of BXCL701 and PEMBRO in Cohort A and B.

  up to 36 months

• Phase 2a: Estimate the median overall survival (OS) of the combination of BXCL701 and PEMBRO in Cohort A and B.

  up to 36 months

• Phase 2a: Estimate the median duration of response (DOR) of the combination of BXCL701 and PEMBRO in Cohort A and B.

  up to 36 months

• Phase 2a: Determine the risk profile of the use of BXCL701 in combination with PEMBRO.

  up to 36 months

Study Arms (4)

Phase 1b

OTHER

Patients will be observed for dose-limiting toxicity (DLT) during Cycle 1. 3 patients will be treated initially with 0.4 mg BXCL701 plus PEMBRO: If there are no DLTs, the dose of BXCL701 will be escalated to 0.6 mg in the next cohort. If ≥1/3 of patients has a DLT in Cycle 1, either 3 patients (if 1 experience a DLT) or 6 to 9 patients (if 2 or 3 experiences a DLT) will be added at the 0.4 mg dose. At the 0.4mg dose: If \<1/3 of the patients experience a DLT, consideration will be given to dose to 0.6 mg BXCL701 plus PEMBRO. If 1/3 of the patients experience a DLT, the Phase 2a can commence. If \>1/3 of the patients experience a DLT, a discussion will be held as to how to proceed. Following 0.6 mg dose. If there are no DLTs, the Phase 2a can commence. If ≥1/3 patients have a DLT in Cycle 1, after a discussion, 6 to 9 patients will be added at the 0.6 mg dose. For this cohort of 6 to 9 patients: If \</=1/3 of the patients experience a DLT, the Phase 2a can commence

Drug: BXCL701 plus Pembrolizumab

Phase 2a

OTHER

After assessment of the safety and confirmation of the BXCL701/+PEMBRO dose schedule to be used in the subsequent stage, the Phase 2a will begin. Eligible patients will receive BXCL701 QD on Days 1 to 14 of a 21-day cycle plus PEMBRO 200 mg administered IV on Day 1 every 21 days.

Drug: BXCL701 plus Pembrolizumab

Phase 2b combination

OTHER

Upon completion of the Phase 2a and achievement of the protocol required composite responses for a given histologic subtype, the Phase 2b enrollment will begin for that subtype. Eligible patients will be randomized to receive: • Combination therapy of BXCL701 on Days 1 to 14 of a 21-day cycle plus PEMBRO 200 mg administered IV on Day 1 of every 21 days.

Drug: BXCL701 plus Pembrolizumab

Phase 2b monotherapy

OTHER

Upon completion of the Phase 2a and achievement of the protocol required composite responses for a given histologic subtype, the Phase 2b enrollment will begin for that subtype. Eligible patients will be randomized to receive: * Monotherapy BXCL701 on Days 1 to 14 of a 21-day cycle. Upon radiographic disease progression with monotherapy, crossover to combination treatment is allowed.

Drug: BXCL701 monotherapy

Interventions

BXCL701 plus Pembrolizumab DRUG

BXCL701 tablets dosage strengths include 0.05mg and 1mg tablets for oral administration. BXCL701 will be administered orally as 0.05mg and 1mg tablets. Patients will take the prescribed number of tablets on Days 1 to 14 of each cycle, for a total daily dose of 0.4 mg, 0.6 mg, or an intermediate dose. BXCL701 will be continued until PD or unacceptable toxicity, or closure of the study by the sponsor; no maximum duration of therapy has been set. BXCL701 should not be taken on an empty stomach. On days when PD studies are being performed, BXCL701 should be administered at the study center and should be administered at approx. the same time of day on each treatment day in the cycle. In cycles in which PD are not evaluated, BXCL701 also should be administered at approx. the same time of day on each treatment day. The PEMBRO dose will be 200 mg, administered as an IV infusion over 30 mins. on Day 1 of each 21-day cycle.

Also known as: BXCL701 plus Pembro

Phase 1b; Phase 2a; Phase 2b combination

BXCL701 monotherapy DRUG

BXCL701 tablets dosage strengths include 0.05mg and 1mg tablets for oral administration. BXCL701 will be administered orally as 0.05mg and 1mg tablets. Patients will take the prescribed number of tablets on Days 1 to 14 of each cycle, for a total daily dose of 0.4 mg, 0.6 mg, or an intermediate dose. BXCL701 will be continued until PD or unacceptable toxicity, or closure of the study by the sponsor; no maximum duration of therapy has been set. BXCL701 should not be taken on an empty stomach. On days when PD studies are being performed, BXCL701 should be administered at the study center and should be administered at approx. the same time of day on each treatment day in the cycle. In cycles in which PD are not evaluated, BXCL701 also should be administered at approx. the same time of day on each treatment day.

Also known as: BXCL701

Phase 2b monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Patient has evidence of progressive, metastatic castration-resistant disease, as defined by PCWG3 criteria.
• a. Patients with de novo small cell prostate cancer are not required to have received androgen deprivation therapy (ADT).
• Progression during or following completion of at least 1 prior line of systemic therapy for locally advanced or metastatic prostate cancer.
• Phases 2a and 2b Only:
• SCNC - Cohort A of Phase 2a only:
• Patient has histologic evidence of SCNC either with archival tissue or a fresh tumor biopsy obtained during screening. 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.
• 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.
• 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
• Has measurable disease per RECIST 1.1 criteria.
• Adenocarcinoma - Cohort B of Phase 2a; randomized population for Phase 2b
• Patient has histologically or cytologically confirmed adenocarcinoma of the prostate without small cell neuroendocrine features.
• Patients with soft tissue disease must provide a fresh core or excisional biopsy or archival tissue 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.
• 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 mCSPC or mCRPC setting. Patients with known actionable mutations should have progressed on applicable standard care targeted therapy or have documented intolerance to or be unsuitable for such therapy.
• RECIST 1.1 measurable disease or detectable bone metastases by whole body bone scintigraphy.
• Patient has serum testosterone \<50 ng/dL during Screening except for those with de novo small cell prostate cancer.

Sponsors & Collaborators

• BioXcel Therapeutics Inc: lead

Study Sites (12)

University of California San Francisco (UCSF)

San Francisco, California, 94158, United States

Location

BioXcel Clinical Research Site

Denver, Colorado, 80211, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

BioXcel Clinical Research Site

Detroit, Michigan, 48201, United States

Location

Center for Advanced Medicine / R.J. Zuckerberg Cancer Center (Northwell Health Cancer Institute)

Lake Success, New York, 11042, United States

Location

Weill Cornell Medicine New York

New York, New York, 10021, United States

Location

White Plains Hospital Center for Cancer Care

White Plains, New York, 10601, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

BioXcel Clinical Research Site

Glasgow, England, G12 0YN, United Kingdom

Location

BioXcel Clinical Research Site

London, Great Britain, W1T 7HA, United Kingdom

Location

BioXcel Clinical Research Site

Sutton, Surrey, SM2 5NG, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neuroendocrine Tumors; Carcinoma, Small Cell

Interventions

PT-100 dipeptide; pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Carcinoma; Neoplasms, Glandular and Epithelial

Study Officials

• Amir Hafeez, MD

  Bioxcel Therapeutics

  STUDY DIRECTOR

• Vincent O'Neill, MD

  Bioxcel Therapeutics

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: April 10, 2019
• Study Start: February 12, 2019
• Primary Completion: October 31, 2023
• Study Completion: December 12, 2024
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); GB (3)