ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer

NCT03480646 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 1205-201
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 41

Brief Summary

This was an open-label Phase 1b/2 study involving oral administration of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone in male patients with metastatic Castration-Resistant Prostate Cancer. The study was designed to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) based on the safety, tolerability, pharmacokinetic, and efficacy profiles of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone. Following the determination of the MTD and RP2D, the study proceeded to Phase 2. Patients in Phase 2 received CPI-1205 at the RP2D in combination with either enzalutamide or abiraterone/prednisone versus either enzalutamide or abiraterone/prednisone as a control arm.

Conditions

Metastatic Castration Resistant Prostate Cancer (mCRPC)

Keywords

Phase 1/2; Oncology; EZH2 Inhibitor

Outcome Measures

Primary Outcomes (4)

• Efficacy: Best Objective Response Rate Percent by Treatment Group

  Best overall response rate (%) defined as complete response (CR) + partial response (PR) divided by the total number of subjects as assessed by Investigator. The response assessment was performed per Prostate Cancer Working Group 3 (PCWG3) based on modifications of the RECIST 1.1 criteria. Per RECIST 1.1, a CR was assessed when all target lesions disappeared (any pathological lymph node must have reduction in short axis to \<10 mm) in the post-baseline scan. A PR was assessed when there was at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 2 years [or until disease progression or unacceptable toxicity]

• Efficacy: Percentage (%) of Subjects With PSA30

  The number of subjects who had a confirmed reduction of 30% of prostate-specific antigen (PSA30) from baseline

  2 years [or until progressive disease or unacceptable toxicity]

• Efficacy: Percentage (%) of Subjects With PSA50

  The number of subjects who had a confirmed reduction of 50% of prostate-specific antigen (PSA50) from baseline

  2 years [or until progressive disease or unacceptable toxicity]

• Efficacy: Composite Response Rate (%) for Phase 2 Randomized and Phase 2 Single-arm Treatment Groups

  Subjects who had a circulating tumor cell of 30% (CTC 30%) or an objective response rate divided by the number of evaluable subjects

  Up to 2 years [or until progressive disease or unacceptable toxicity]

Secondary Outcomes (2)

• Efficacy: Best Responses by Treatment Group

  Up to 2 years [or until disease progression or unacceptable toxicity]

• Safety: Number of Participants With Treatment-emergent AEs Leading to Treatment Discontinuation

  Up to 2 years [or until clinical progression, radiographic disease progression, or until unacceptable toxicity]

Study Arms (8)

Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza

EXPERIMENTAL

CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Enzalutamide 160 mg PO QD (28-day cycles)

Drug: CPI-1205; Drug: Cobicistat; Drug: Enzalutamide

Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred

EXPERIMENTAL

CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)

Drug: CPI-1205; Drug: Cobicistat; Drug: Abiraterone; Drug: Prednisone

Phase 1b Dose Escalation: CPI-1205 800 mg TID + Enza

EXPERIMENTAL

CPI-1205 800 mg TID in combination with Enzalutamide 160 mg PO QD (28-day cycle)

Drug: CPI-1205; Drug: Enzalutamide

Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred

EXPERIMENTAL

CPI-1205 800 mg TID in combination with Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle)

Drug: CPI-1205; Drug: Abiraterone; Drug: Prednisone

Phase 1b HPEC: CPI-1205 800 mg TID + Enza

EXPERIMENTAL

CPI-1205 800 mg TID highly pretreated expansion cohort (HEPC) in combination with Enzalutamide 160 mg PO QD (28-day cycles)

Drug: CPI-1205; Drug: Enzalutamide

Phase 2 Randomized Controlled Group: Enza

ACTIVE COMPARATOR

Drug: Enzalutamide 160mg PO QD (28-day cycles)

Drug: Enzalutamide

Phase 2 Randomized at RP2D: CPI-1205 800 mg TID + Enza

EXPERIMENTAL

CPI-1205 (at Recommended Phase 2 Dose \[RP2D\]) in combination with Drug: Enzalutamide 160 mg PO QD

Drug: CPI-1205; Drug: Enzalutamide

Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred

EXPERIMENTAL

CPI-1205 at 800 mg TID (Recommended Phase 2 Dose \[RP2D\]) 800 mg TID in combination with Abiraterone 1000 mg PO QD and Prednisone 5 mg PO BID (28-day cycles)

Drug: CPI-1205; Drug: Abiraterone; Drug: Prednisone

Interventions

CPI-1205 DRUG

CPI-1205: Either 400 mg BID or 800 mg TID during Phase 1 dose-escalation and RP2D, 800 mg TID, for Phase 2

Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza; Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred; Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred; Phase 1b Dose Escalation: CPI-1205 800 mg TID + Enza; Phase 1b HPEC: CPI-1205 800 mg TID + Enza; Phase 2 Randomized at RP2D: CPI-1205 800 mg TID + Enza; Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred

Cobicistat DRUG

Cobicistat 150 mg PO BID

Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza; Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred

Enzalutamide DRUG

Enzalutamide 160mg PO QD

Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza; Phase 1b Dose Escalation: CPI-1205 800 mg TID + Enza; Phase 1b HPEC: CPI-1205 800 mg TID + Enza; Phase 2 Randomized Controlled Group: Enza; Phase 2 Randomized at RP2D: CPI-1205 800 mg TID + Enza

Abiraterone DRUG

Abiraterone 1000mg PO QD

Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred; Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred; Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred

Prednisone DRUG

Prednisone 5mg PO BID

Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred; Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred; Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred

Eligibility Criteria

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

You may qualify if:

• Patients must meet all the following criteria to be enrolled in this study:
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Life expectancy of at least 12 weeks
• Histologically or cytologically confirmed adenocarcinoma of the prostate (pure small cell carcinoma excluded)
• Documented metastatic disease
• Must have undergone bilateral orchiectomy (surgical castration) or willing to continue gonadotropin-releasing hormone (GnRH) analog or antagonist (medical castration)
• Serum testosterone \< 50 ng/dL
• Progressive disease in the setting of medical or surgical castration (i.e., Castration-resistant Prostate Cancer \[CRPC\]) as assessed by the investigator and includes at least one of the following:
• Evidence of progression as measured by PSA increase of ≥ 25% and an absolute increase of ≥ 2 ng/mL in \< 6 months from end of last therapy prior to enrollment and/or
• Soft tissue disease progression as per Response Evaluation Criteria in Solid Tumors (RECIST) and/or
• Bone disease progression defined by two or more new lesions on bone scan
• Bisphosphonate or denosumab therapy allowed provided dose has been stable for at least 4 weeks prior to Day 1 of treatment
• Prior treatment:
• Prior treatment for metastatic CRPC (mCRPC) must have included at least one line with a second-generation androgen inhibitor (e.g., abiraterone, enzalutamide, apalutamide, daralutamide)

You may not qualify if:

• Patients who meet any of the following criteria will not be enrolled in the study:
• Known symptomatic brain metastases
• Treatment with any of the following for prostate cancer within the indicated timeframe prior to Day 1 of treatment
• First generation: AR antagonists (e.g., bicalutamide, nilutamide, flutamide) within 4 weeks
• alpha reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol \[DES\]), or progesterones within 2 weeks
• Chemotherapy within 3 weeks
• Biologic therapy within 4 weeks
• Investigational therapy within 3 weeks (or within a time interval less than at least 5 half-lives of the investigational agent \[if known\], whichever is longer).
• Immunotherapy within 4 weeks
• Radionuclide therapy within 4 weeks
• Radiation therapy for the treatment of metastasis within 1 week prior to Day 1 of treatment
• Herbal products that may decrease PSA levels within 4 weeks prior to day 1 of treatment
• Systemic steroids greater than 10 mg of prednisone/prednisolone per day within 4 weeks prior to day 1 of treatment
• Major surgery within 4 weeks prior to Day 1 of treatment
• Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery

Sponsors & Collaborators

• Constellation Pharmaceuticals: lead

Study Sites (41)

Alaska Urological Institute

Anchorage, Alaska, 99503, United States

Location

Beverly Hills Cancer Center (BHCC)

Beverly Hills, California, 90211, United States

Location

John Wayne Cancer Inst.

Duarte, California, 91010, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

Rocky Mountain Cancer Centers

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

University of Florida

Jacksonville, Florida, 32209, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami, Florida, 33140, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois Hospital and Health Systems

Chicago, Illinois, 60612, United States

Location

Indiana University- Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

John Hopkins Kimmel Cancer Center

Baltimore, Maryland, 21205, United States

Location

Maryland Oncology Hematology

Rockville, Maryland, 20850, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

GU Research Network

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89135, United States

Location

New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

North Shore Hematology Oncology Associates

East Setauket, New York, 11733, United States

Location

NYU Langone Medical Center Laura and Isaac Permlutter Cancer Center

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mt. Sinai

New York, New York, 10029, United States

Location

Eastchester Center for Cancer Care

The Bronx, New York, 10469, United States

Location

University of North Carolina-Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 22710, United States

Location

Ohio State University - James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

Location

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

Location

Williamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

Location

Compass Oncology - East

Tualatin, Oregon, 97062, United States

Location

St. Luke's University

Bethlehem, Pennsylvania, 18015, United States

Location

Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17331, United States

Location

Greenville Hospital System, Institute for Translational Oncology Research

Greenville, South Carolina, 29605, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Texas Oncology - Central Austin Cancer Center

Austin, Texas, 78731, United States

Location

Texas Oncology- Fort Worth

Fort Worth, Texas, 76104, United States

Location

Texas Oncology- Tyler

Tyler, Texas, 75702, United States

Location

Virginia Oncology Associates

Hampton, Virginia, 23666, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

(R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide; Cobicistat; enzalutamide; abiraterone; Prednisone

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Clinical Program Lead
• Organization: Constellation, Inc.

medinfo@morphosys.com

1-844-667-1992

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

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: March 7, 2018
• First Posted: March 29, 2018
• Study Start: November 15, 2017
• Primary Completion: February 3, 2021
• Study Completion: February 3, 2021
• Last Updated: October 29, 2025
• Results First Posted: October 29, 2025

Record last verified: 2025-10

Locations

US (41)