I-131-1095 Radioligand Plus Enzalutamide vs Enzalutamide for mCRPC That Progressed During Abiraterone (ARROW).

NCT03939689 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1095-2301
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 27

Brief Summary

This clinical trial was done to show whether a radioactive drug (I-131-1095) that binds to prostate-specific membrane antigen (PSMA) is useful in treating metastatic prostate cancer that is positive for PSMA. The trial enrolled men whose PSMA-positive metastatic prostate cancer had progressed while they were taking abiraterone. During the trial, all of the men took enzalutamide (standard-of-care therapy) once a day. However, some of the men also had up to 4 doses (8 weeks apart) of I-131-1095 (in addition to taking enzalutamide once a day). At specified times during the trial, all of the men had blood tests (to measure levels of prostate-specific antigen \[PSA\]) and imaging studies (to assess tumor status). The two groups of men were then compared in several ways. The main comparison was the percentage of men in each group with at least a 50% decrease in PSA levels. Other comparisons involved the response of the tumors (as seen on imaging) and overall survival. To assess safety, the number of adverse events in both groups were also compared.

Conditions

Metastatic Prostate Cancer; Castration-resistant Prostate Cancer; Prostatic Neoplasm; Cancer of the Prostate; Progressive mCRPC

Keywords

bone metastases; 18F-DCFPyL; PSMA PET; PSMA-avidity; biomarker; radioligand therapy; adjunct radiation therapy; dosimetry; SPECT/CT; docetaxel

Outcome Measures

Primary Outcomes (1)

• PSA Response Rate

  The percentage of participants with a PSA response according to PCWG3 criteria. PCWG3 defines PSA response as the first occurrence of a 50 percent or more decline in PSA from baseline, confirmed by a second measurement at least 3 weeks later.

  Up to 53 weeks

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  Up to 53 weeks

• Radiographic Progression Free Survival (rPFS)

  Up to 5 years.

• Overall Survival (OS)

  Up to 5 years

• PSA Progression

  Up to 53 weeks

• Duration of Response

  Up to 5 years.

Study Arms (2)

Enzalutamide

ACTIVE COMPARATOR

Participants received the label dosage of enzalutamide once daily for up to 53 weeks.

Drug: Enzalutamide

I-131-1095 in combination with enzalutamide

EXPERIMENTAL

Participants received up to 4 (8-week) cycles of I-131-1095: 100 mCi for the first dose. Subsequent dose(s) were reduced to 75 mCi for participants experiencing any of the dose-limiting toxicities. The third and fourth therapeutic doses could be reduced to 75 mCi on the basis of dosimetry assessment after administration of 10 mCi of I-131-1095 prior to the third dosing cycle. Participants also received the label dosage of enzalutamide once daily for up to 53 weeks.

Drug: I-131-1095; Drug: Enzalutamide

Interventions

I-131-1095 DRUG

Participants received up to 4 (8-week) cycles of I-131-1095: 100 mCi for the first dose. Subsequent dose(s) were reduced to 75 mCi for participants experiencing any dose-limiting toxicities. The third and fourth therapeutic doses could be reduced to 75 mCi on the basis of dosimetry assessment after administration of 10 mCi of I-131-1095 prior to the third dosing cycle. Participants also received the label dosage of enzalutamide once daily for up to 53 weeks.

Also known as: 131 I-PSMA-1095, 131I-LNTH-1095

I-131-1095 in combination with enzalutamide

Enzalutamide DRUG

Participants received the label dosage of enzalutamide once daily for up to 53 weeks.

Also known as: Xtandi

Enzalutamide; I-131-1095 in combination with enzalutamide

Eligibility Criteria

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

You may qualify if:

• Male ≥ 18 years of age
• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features at initial diagnosis
• Castration-resistant prostate cancer, with serum testosterone ≤ 50 ng/dL at Screening
• Radiographic evidence of metastatic disease prior to Randomization or up to 21 days prior to Screening
• Disease progression on prior abiraterone therapy as defined by meeting at least one of the following criteria per the investigator:
• PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart
• Soft tissue disease progression defined by RECIST 1.1
• Bone disease progression defined by two or more new lesions on bone scan
• Planned to receive treatment with enzalutamide
• Subjects who are ineligible or choose not to receive taxane-based chemotherapy based on personal preference or physician opinion. Examples of conditions that could make a patient ineligible or refuse to receive taxane-based chemotherapy, but would allow them to still be eligible to receive I-131-1095 include the following:
• Poor performance status
• Prior intolerance to cytotoxic agents
• History of another malignancy suspected for recurrence or metastases
• Other serious medical conditions such as symptomatic peripheral neuropathy CTCAE Grade 2 or higher; or clinically significant cardiovascular disease per the Investigator or treating physician
• Subjects receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Randomization

You may not qualify if:

• Received any anti-tumor therapy within 4 weeks of Randomization, with the exception of abiraterone, GnRH therapy and non-radioactive bone-targeted agents
• Received prior chemotherapy for castration-resistant prostate cancer
• Superscan as evidenced on baseline bone scan
• Treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 within 6 months prior to Randomization
• Prior hemi-body irradiation
• Prior PSMA-targeted radioligand therapy
• Major surgery within 4 weeks of Randomization
• Impaired organ function as evidenced by the following laboratory values at Screening:
• Absolute neutrophil count \< 1500 μL
• Platelet count \< 100,000/μL
• Hemoglobin \< 9.5 g/dL
• Albumin \< 3.0 g/dL (30 g/L)
• Total bilirubin \> 2 x ULN unless in instances of known or suspected Gilbert's disease
• AST or ALT \> 2.5 x ULN
• Calculated creatinine clearance (CrCL) \< 30 mL/min (Cockroft-Gault equation), or currently on renal dialysis.

Sponsors & Collaborators

• Progenics Pharmaceuticals, Inc.: lead

Study Sites (27)

City of Hope

Duarte, California, 91010, United States

Location

VA Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

UCLA

Los Angeles, California, 90095-7370, United States

Location

Hoag Family Cancer Institute

Newport Beach, California, 92663, United States

Location

VA Palo Alto Healthcare System

Palo Alto, California, 94303, United States

Location

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Tulane Medical School

New Orleans, Louisiana, 70112, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

LifeSpan Cancer Institute

Providence, Rhode Island, 09206, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

London Health Sciences Centre

Toronto, Ontario, Canada

Location

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

Centre Hospitalier Del' Universite de Montreal

Montreal, Quebec, Canada

Location

Jewish General Hospital

Montreal, Quebec, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Location

Related Publications (2)

• Afshar-Oromieh A, Haberkorn U, Zechmann C, Armor T, Mier W, Spohn F, Debus N, Holland-Letz T, Babich J, Kratochwil C. Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with 131I-MIP-1095. Eur J Nucl Med Mol Imaging. 2017 Jun;44(6):950-959. doi: 10.1007/s00259-017-3665-9. Epub 2017 Mar 9.

  PMID: 28280855 BACKGROUND

• Zechmann CM, Afshar-Oromieh A, Armor T, Stubbs JB, Mier W, Hadaschik B, Joyal J, Kopka K, Debus J, Babich JW, Haberkorn U. Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014 Jul;41(7):1280-92. doi: 10.1007/s00259-014-2713-y. Epub 2014 Feb 28.

  PMID: 24577951 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: June Li, Vice President, Biometrics and Data Sciences
• Organization: Lantheus

lij@lantheus.com

978-671-8107

Study Officials

• Jean-Claude Provost, MD

  Progenics Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study population includes patients with PSMA-avid mCRPC whose disease has progressed despite abiraterone therapy, and are planned for treatment with enzalutamide.

Study Record Dates

• First Submitted: May 3, 2019
• First Posted: May 7, 2019
• Study Start: May 30, 2019
• Primary Completion: September 21, 2023
• Study Completion: September 24, 2024
• Last Updated: October 14, 2025
• Results First Posted: October 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (20); CA (7)