RECRUITING

A Study of Tarlatamab for People With Prostate Cancer

Conditions

Metastatic Prostate Cancer Tarlatamab Delta-like protein expression 3 (DLL3)25-138

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The researchers are doing this study to find out whether tarlatamab is an effective treatment for Delta-like Protein 3 (DLL3)-positive prostate cancer that has spread to other parts of your body (metastasized) and has either come back after treatment (relapsed) or not responded to treatment (refractory).

Official Title

TIDAL: Phase 2 Study of Tarlatamab in Patients With Delta-like Protein 3 (DLL3) Positive Metastatic Prostate Cancer

Quick Facts

Study Start:2025-07-31

Study Completion:2027-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07111507

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* To be included in this study, participants should complete all screening procedures and meet all of the following criteria: * Willing and able to provide, or have a legally authorized representative provide, written informed consent and privacy authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed. * 18 years of age and above * Resting oxygen saturation of ≥ 90% on room air. * Histologically confirmed prostate cancer. Any histologic subtype of prostate cancer is allowed. * Documented metastatic disease based on conventional imaging (soft tissue disease on computed topography (CT)/magnetic resonance imaging (MRI), or at least 2 lesions as found on bone scan) obtained during Screening. Metastatic disease as seen only on PET scan is exclusionary. Metastatic disease may include pelvic lymph nodes above and/or below the aortic bifurcation. * Serum testosterone ≤ 50 ng/dL with ongoing androgen-deprivation therapy (ADT) or de novo small cell NEPC (neither testosterone levels nor ADT are required in participants with de novo small cell NEPC). * Progression on at least one line of therapy in the metastatic setting based on at least one of the following criteria: 1. Prostate-specific antigen (PSA) progression defined as a minimum of 2 rising PSA levels with a minimum of a 1-week interval between each determination. There is no minimum PSA level required. 2. Nodal or visceral progression as defined by RECIST 1.1 with PCWG3 modifications 3. Progression of bone disease with two or more new bone lesions on bone scan (i.e., PCWG3) * Participants with de novo small cell NEPC are required to have received prior platinum-based chemotherapy or be ineligible for this treatment. * No more than two prior lines of cytotoxic chemotherapy in the metastatic castration-resistant disease setting or the de novo small cell NEPC setting * DLL3 positive disease as defined by archival or fresh tumor biopsy with positive DLL3 expression using a CLIA certified assay (50% or more of tumor cells with DLL3 expression by IHC). DLL3 testing may be obtained at any point prior to study enrollment * Participants with brain metastases are eligible provided definitive treatment completed at least two weeks prior to C1D1, no concurrent steroids for the treatment of central nervous system (CNS) disease, and no progression noted on CNS imaging obtained during screening obtained following completion of definitive treatment. * ECOG status of ≤ 2 * Normal organ function with acceptable initial laboratory values within 14 days of treatment start. Red blood cell transfusions during screening may be allowed if laboratory values initially fall outside of the following ranges: * Absolute neutrophil count (ANC) ≥ 1,500/μ * Hemoglobin ≥9g/dL * Platelet count ≥75,000/μl * Bilirubin ≤ 1.5 upper limit of normal (ULN) or \< 2 if liver metastases or Gilbert's disease * SGOT (AST) \< 3 x ULN or \< 5 if liver metastases * SGPT (ALT) \< 3 x ULN or \< 5 if liver metastases * Adequate renal function CrCl ≥ 30mL/min using Cockroft Gault or MDRD calculation * Participants must agree to use a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study, including 60 days after the last dose of study drug. Sperm donation is prohibited during the study and for 60 days after the last dose of study drug. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.	* Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessments in the judgment of the site Principal Investigator (PI). * Medical conditions such as uncontrolled hypertension (sustained SBP \> 160 mm Hg or diastolic BP \> 100 mm Hg), any history of seizure, or major cardiovascular event (myocardial infarction), stroke or transient ischemia event within 6 months prior to study entry, or NYHA class ≥ III congestive heart failure, or uncontrolled cardiac arrhythmia. * Active hepatitis B or C infection (defined as positive HBsAg or positive HBV DNA in participants who are HBV core Ab +; detectable HCV RNA by PCR). Prior treatment for HBV or HCV is allowed. * Active human immunodeficiency (HIV) infection on antiviral therapy as measured by a detectable viral load. * History of leptomeningeal disease. * Active autoimmune disease requiring systemic treatment within the past 2 years or Grade \> 2 autoimmune adverse effect from prior immune checkpoint inhibition (exception: any grade endocrine disorders on replacement treatment are allowed). Prednisone or equivalent at doses of up to 10 mg/day along with oral weekly methotrexate are allowed. No other immunosuppressive medications are allowed * History of interstitial lung disease and/or Grade ≥ 2 pneumonitis at the time of study entry * Diagnosis of immunodeficiency or receiving systemic steroid therapy (prednisone \> 10 mg/day or equivalent) within 7 days of C1D1 * Presence of infection requiring IV antibiotics within 7 days of C1D1 * Prior DLL3-targeting treatment * Systemic anti-cancer treatment (other than LHRH analog) within 14 days or 5 half-lives, whichever is shorter, prior to C1D1 * Receipt of another investigational therapeutic agent within 14 days or 5 half-lives, whichever is shorter, prior to C1D1 * Major surgical procedure within 28 days prior to C1D1 * Palliative radiotherapy if \< 1 week prior to C1D1 * Use of any prohibited concomitant medications (Appendix C: Medications With the Potential for Drug-Drug Interactions) within two weeks prior to C1D1. * Grade \> 2 treatment-related adverse event related to prior therapy that is ongoing at the start of study treatment. * Known allergy to any of the compounds under investigation * Any other condition which, in the opinion of the Investigator, would preclude participation in this trial

Inclusion Criteria

Exclusion Criteria

* To be included in this study, participants should complete all screening procedures and meet all of the following criteria:
* Willing and able to provide, or have a legally authorized representative provide, written informed consent and privacy authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.
* 18 years of age and above
* Resting oxygen saturation of ≥ 90% on room air.
* Histologically confirmed prostate cancer. Any histologic subtype of prostate cancer is allowed.
* Documented metastatic disease based on conventional imaging (soft tissue disease on computed topography (CT)/magnetic resonance imaging (MRI), or at least 2 lesions as found on bone scan) obtained during Screening. Metastatic disease as seen only on PET scan is exclusionary. Metastatic disease may include pelvic lymph nodes above and/or below the aortic bifurcation.
* Serum testosterone ≤ 50 ng/dL with ongoing androgen-deprivation therapy (ADT) or de novo small cell NEPC (neither testosterone levels nor ADT are required in participants with de novo small cell NEPC).
* Progression on at least one line of therapy in the metastatic setting based on at least one of the following criteria:
1. Prostate-specific antigen (PSA) progression defined as a minimum of 2 rising PSA levels with a minimum of a 1-week interval between each determination. There is no minimum PSA level required.
2. Nodal or visceral progression as defined by RECIST 1.1 with PCWG3 modifications
3. Progression of bone disease with two or more new bone lesions on bone scan (i.e., PCWG3)
* Participants with de novo small cell NEPC are required to have received prior platinum-based chemotherapy or be ineligible for this treatment.
* No more than two prior lines of cytotoxic chemotherapy in the metastatic castration-resistant disease setting or the de novo small cell NEPC setting
* DLL3 positive disease as defined by archival or fresh tumor biopsy with positive DLL3 expression using a CLIA certified assay (50% or more of tumor cells with DLL3 expression by IHC). DLL3 testing may be obtained at any point prior to study enrollment
* Participants with brain metastases are eligible provided definitive treatment completed at least two weeks prior to C1D1, no concurrent steroids for the treatment of central nervous system (CNS) disease, and no progression noted on CNS imaging obtained during screening obtained following completion of definitive treatment.
* ECOG status of ≤ 2
* Normal organ function with acceptable initial laboratory values within 14 days of treatment start. Red blood cell transfusions during screening may be allowed if laboratory values initially fall outside of the following ranges:
* Absolute neutrophil count (ANC) ≥ 1,500/μ
* Hemoglobin ≥9g/dL
* Platelet count ≥75,000/μl
* Bilirubin ≤ 1.5 upper limit of normal (ULN) or \< 2 if liver metastases or Gilbert's disease
* SGOT (AST) \< 3 x ULN or \< 5 if liver metastases
* SGPT (ALT) \< 3 x ULN or \< 5 if liver metastases
* Adequate renal function CrCl ≥ 30mL/min using Cockroft Gault or MDRD calculation
* Participants must agree to use a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study, including 60 days after the last dose of study drug. Sperm donation is prohibited during the study and for 60 days after the last dose of study drug. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.

* Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessments in the judgment of the site Principal Investigator (PI).
* Medical conditions such as uncontrolled hypertension (sustained SBP \> 160 mm Hg or diastolic BP \> 100 mm Hg), any history of seizure, or major cardiovascular event (myocardial infarction), stroke or transient ischemia event within 6 months prior to study entry, or NYHA class ≥ III congestive heart failure, or uncontrolled cardiac arrhythmia.
* Active hepatitis B or C infection (defined as positive HBsAg or positive HBV DNA in participants who are HBV core Ab +; detectable HCV RNA by PCR). Prior treatment for HBV or HCV is allowed.
* Active human immunodeficiency (HIV) infection on antiviral therapy as measured by a detectable viral load.
* History of leptomeningeal disease.
* Active autoimmune disease requiring systemic treatment within the past 2 years or Grade \> 2 autoimmune adverse effect from prior immune checkpoint inhibition (exception: any grade endocrine disorders on replacement treatment are allowed). Prednisone or equivalent at doses of up to 10 mg/day along with oral weekly methotrexate are allowed. No other immunosuppressive medications are allowed
* History of interstitial lung disease and/or Grade ≥ 2 pneumonitis at the time of study entry
* Diagnosis of immunodeficiency or receiving systemic steroid therapy (prednisone \> 10 mg/day or equivalent) within 7 days of C1D1
* Presence of infection requiring IV antibiotics within 7 days of C1D1
* Prior DLL3-targeting treatment
* Systemic anti-cancer treatment (other than LHRH analog) within 14 days or 5 half-lives, whichever is shorter, prior to C1D1
* Receipt of another investigational therapeutic agent within 14 days or 5 half-lives, whichever is shorter, prior to C1D1
* Major surgical procedure within 28 days prior to C1D1
* Palliative radiotherapy if \< 1 week prior to C1D1
* Use of any prohibited concomitant medications (Appendix C: Medications With the Potential for Drug-Drug Interactions) within two weeks prior to C1D1.
* Grade \> 2 treatment-related adverse event related to prior therapy that is ongoing at the start of study treatment.
* Known allergy to any of the compounds under investigation
* Any other condition which, in the opinion of the Investigator, would preclude participation in this trial

Contacts and Locations

Study Contact

Karen Autio, MD

CONTACT

646-422-4632

autiok@mskcc.org

Michael Morris, MD

CONTACT

646-422-4469

Principal Investigator

Karen Autio, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Karen Autio, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-07-31

Study Completion Date2027-08-31

Study Record Updates

Study Start Date2025-07-31

Study Completion Date2027-08-31

Terms related to this study

Keywords Provided by Researchers

Tarlatamab
Delta-like protein expression 3 (DLL3)
25-138

Additional Relevant MeSH Terms

Metastatic Prostate Cancer