RecruitingInterventionalPhase 2

A Phase II Clinical Trial to Evaluate the Efficacy and Safety of Fam-Trastuzumab Deruxtecan-Nxki (T-DXd) as a Subsequent Line of Therapy in HER2-Positive Metastatic Castration-Resistant Prostate Adenocarcinoma

NCT ID: NCT06610825Sponsor: Washington D.C. Veterans Affairs Medical CenterLast updated: 2026-04-13

Summary

Use of Enhertu as a Subsequent Line of Therapy in HER2-Positive Metastatic Castration-Resistant Prostate Adenocarcinoma.

Detailed description

This Phase II clinical trial aims to evaluate the efficacy and safety of Enhertu in HER-2 positive mCRPC who have progressed on prior androgen deprivation therapy and novel hormonal agents, who are either not candidates for or have refused taxane based chemotherapy. Led by Dr. Maneesh Jain at the Washington DC VA, the open label multi center study will include 60 participants treated with Enhertu. Primary endpoints focus on objective response rates, while secondary measures include safety, progression-free survival, overall survival, and quality of life.

Arms & interventions

DrugEnhertu
This is an open label, multi-center, single arm, phase II study designed to investigate the anti-tumor activity, efficacy and safety of Enhertu in HER2-positive metastatic castrate-resistant prostate cancer patients who progressed on androgen deprivation therapy and novel hormonal agents (such as Abiraterone and Enzalutamide), who also progressed, refused, or were not candidates to receive taxane-based chemotherapy.

Outcome measures

Primary

ORR
Objective Response Rate by local review, combining radiographic and biochemical responses
Time frame: 2 years

Secondary

Progression Free Survival
Time frame: 2 years
Overall Survival
Time frame: 2 years
Disease Control Rate
Time frame: 2 years
Duration of Response
Time frame: 2 years

Eligibility criteria

Sex: MaleAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * Pathologically confirmed adenocarcinoma of the prostate * Diagnosis of mCRPC * Documented progression on androgen deprivation and novel hormonal agents, with or without progression on taxane containing regimen * Ongoing ADT to maintain serum testosterone levels below 50 ng/dL * Formalin fixed paraffin embedded tumor tissue for HER2 immunohistochemistry * Life expectancy 6 months * ECOG 0 or 1 * LVEF at least 50% * Adequate Blood Clotting function * Adequate Organ and Bone Marrow function * Adequate Renal function * Adequate Hepatic function Exclusion Criteria: * History of interstitial lung disease or pneumonitis requiring steroids * Significant coronary vascular disease * Previous exposure to HER2 targeted therapy

Study locations (1)

Washington DC VAMC

Washington D.C., District of Columbia, 20422

Recruiting

Asha Escobar · Contact

2027431090 asha.escobar@Va.gov

Maneesh Jain, MD · Principal Investigator

References

Zamalloa N, Rose J, Lap CJ, Rajendran R, Estephan F, Jatwani K, Poudel A, Subrahmanyam R, Hurley PJ, Nava VE, Jain M. Historical Perspective of HER2 Testing and Treatment in Prostate Cancer. Curr Oncol. 2026 Feb 2;33(2):91. doi: 10.3390/curroncol33020091.(PubMed)
Rajendran R, Lap CJ, Madapoosi S, Heiraty A, Estephan F, Hahn W, Poudel A, Nava VE, Subrahmanyam R, Jain M. Clinical response to novel combination of trastuzumab deruxtecan and abiraterone in HER2-expressing metastatic castration-resistant prostate cancer. Oncologist. 2025 Sep 1;30(9):oyaf207. doi: 10.1093/oncolo/oyaf207.(PubMed)
Lap CJ, Rajendran R, Martin JM, Uppal M, Escobar A, Heiraty AM, Estephan F, Hahn W, Subrahmanyam R, Nava VE, Jain M. Response of Human Epidermal Growth Factor Receptor 2-Expressing Prostate Cancer to Trastuzumab Deruxtecan. Ann Intern Med. 2024 Dec;177(12):1738-1741. doi: 10.7326/ANNALS-24-01409. Epub 2024 Nov 5. No abstract available.(PubMed)
Estephan F, Lap CJ, Banagan J, Antonio M, Liu S, Diao G, Rozalen AZ, Rajendran R, Krasnow S, Subrahmanyam R, Nava VE, Jain M. The prevalence and clinical significance of HER2 expression in prostate adenocarcinoma. Ann Diagn Pathol. 2023 Dec;67:152219. doi: 10.1016/j.anndiagpath.2023.152219. Epub 2023 Oct 20.(PubMed)