ASCO 2023: PSMAddition: A Phase 3 Trial to Compare Treatment with 177Lu-PSMA-617 + Standard of Care and Standard of Care Alone in Patients with mHSPC

(UroToday.com) The 2023 ASCO annual meeting included a prostate cancer session, featuring a trials in progress presentation by Dr. Scott Tagawa discussing PSMAddition, a phase 3 trial comparing 177Lu-PSMA-617 + standard of care and standard of care alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC). PSMA is a promising theranostic target for prostate cancer, owing to its expression in around 90% of all prostate cancers and its limited expression in non-prostate cancer tissue. 177Lu-PSMA-617 is a high affinity PSMA-targeted radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and their surrounding environment. In the phase 3 VISION study,1 177Lu-PSMA-617 + protocol-permitted standard of care significantly improved radiographic progression-free survival and overall survival in patients with PSMA-positive metastatic castration-resistant prostate cancer, previously treated with at least one androgen receptor pathway inhibitor and one or two taxanes. However, ADT and androgen receptor pathway inhibitors may alter PSMA expression and radiosensitivity. As such, PSMAddition will assess the efficacy and safety of 177Lu-PSMA-617 plus standard of care versus standard of care alone in adults with mHSPC.

 

PSMAddition (NCT04720157) is an international, prospective, open-label, randomized, phase 3 trial that will enroll an estimated 1,126 patients with treatment-naïve or minimally treated PSMA-positive mHSPC. Eligible patients are treatment-naive or minimally treated candidates for hormonal therapy, with PSMA-positive disease (determined by 68Ga-PSMA-11 PET/CT), ECOG performance status of 0 to 2, and adequate major organ function. Patients are excluded if they have rapidly progressing tumors that require chemotherapy. Patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq every 6 weeks for a maximum of 6 cycles) + standard of care or standard of care alone (an androgen receptor pathway inhibitor and ADT). The study design for PSMAddition is as follows:

ASCO 2023_Tagawa_PSMAAddition_0 

Stratification factors are tumor volume (high/low), age (≥ 70/ < 70 years), and previous/planned prostatectomy or radiation treatment of the primary prostate tumor (yes/no). Recruitment for a China extension cohort (40–60 patients) will follow after completion of main study recruitment. The primary endpoint is radiographic progression-free survival, as assessed by blinded independent centralized review. Upon centrally confirmed radiographic progression, participants in the standard of care-only arm can cross over to the 177Lu-PSMA-617 arm. The planned sample size provides 95% power to detect a hazard ratio of 0.7 for radiographic progression-free survival after 418 events with an overall one-sided significance level of 0.025.

Secondary endpoints include:

  • Overall survival
  • Proportion of patients with a PSA decline of ≥ 90% from baseline
  • Time to development of metastatic castration-resistant prostate cancer
  • Composite PFS (radiographic, clinical or PSA progression)
  • Safety
  • Tolerability
  • Health-related quality of life

Imaging and biospecimen (tissue and blood) collection is embedded for correlative analysis. Participants who have received 177Lu-PSMA-617 will have the option to enroll in a separate long-term safety follow-up study. The first participant was enrolled into the study on June 9, 2021. In total, 19 countries are participating in PSMAddition:

ASCO 2023_Tagawa_PSMAAddition_1 

As of May 2023, 176 centers are recruiting patients to the study, with an estimated study completion data of February 2026.

 

Presented by: Scott T. Tagawa, M.D., MS, FACP, Weill Cornell Medicine, New York, NY

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.

References:

  1. Sartor O, de Bono J, Chi KN et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103.