1604P - PSMA-targeted radioligand therapy (RLT) with 131I-LNTH-1095 (1095) plus enzalutamide (enza) vs enza alone in chemotherapy-naïve patients (pts) whose piflufolastat F 18-avid metastatic castration-resistant prostate cancer (mCRPC) progressed on abiraterone (abi): ARROW

Background

In nonclinical studies, prostate-specific membrane antigen (PSMA)-targeted RLT plus androgen antagonist had synergistic cytotoxic effects on prostate cancer (PCa) cells.

Methods

ARROW recruited mCRPC pts (≥18 years) who were to receive enza after progression on abi. mCRPC was confirmed by histopathology and PSMA-PET avidity (piflufolastat F 18), while RECIST 1.1 and Prostate Cancer Working Group 3 (PCWG3) criteria were applied. Pts were randomized 2:1 to either enza (160 mg QD) plus 1095 (100 mCi dose, then up to 4 cycles ≥8 weeks apart, as determined by dosimetry and dose-limiting events) or enza. The primary endpoint was prostate-specific antigen response rate (PSA RR): first occurrence of ≥50% decline in PSA from baseline, confirmed by a second measurement ≥3 weeks later. Secondary endpoints included radiographic-progression–free survival (rPFS), overall response rate (ORR), landmark overall survival (OS), PSA progression (PCWG3 criteria), duration of response, & safety. The primary endpoint assumed a RR of 59% for 1095+enza and 30% for enza. With 2:1 randomization and anticipated 15% dropout, ≥102 pts were needed to provide 80% power for a 2-sided χ² test (α=0.05). A 2-sided Cochran-Mantel-Haenszel χ² test stratified by risk category was used for the primary endpoint.

Results

Of 177 screened pts, 120 were randomized to enza+1095 (n=80) or enza (n=40). Patient characteristics in both arms were similar at baseline. PSA RR was 62.86% for enza+1095 pts vs 31.25% for enza pts (p=0.0025). Median rPFS was 14.0 months (95% CI: 8.64-18.20) for enza+1095 vs 11.5 months (2.79-18.43) for enza (p=0.1032). Incidence of TEAEs of grade ≥3 was 65.8% (enza+1095) vs 41.0% (enza). Most frequent TEAEs for enza+1095 vs enza, respectively, were fatigue (75.0%, 53.8%), nausea (59.2%, 33.3%), and decreased appetite (48.7, 17.9%).

Conclusions

There was statistically and clinically significant improvement in PSA RR for enza+1095 vs enza alone.

Clinical trial identification

NCT03939689.

Editorial acknowledgement

Writing and editorial support were provided by Vincent DiPippo of Progenics Pharmaceuticals, a Lantheus company, and Laurie Thomas of Winfield Consulting.

Legal entity responsible for the study

Lantheus Lantheus.

Funding

Lantheus.

Disclosure

E.Y. Yu: Other, Personal, Speaker, Consultant, Advisor: Jansen, Merck, AAA Novartis, Bayer, Aadi Bioscience, Oncternal, BMS, Loxo, Lantheus; Non-Financial Interests, Institutional, Speaker, Consultant, Advisor: Dendreon, Merck, Seagen, Blue Earth, Bayer, Lantheus, Tyra, Oncternal. V. Narayan: Other, Personal, Speaker, Consultant, Advisor: Ferring Pharmaceutials, Ciox; Other, Institutional, Research Funding: Ferring; Financial Interests, Institutional, Research Funding: Ciox. G. Esposito: Other, Personal, Speaker’s Bureau: Lantheus. R. Szmulewitz: Other, Personal, Speaker, Consultant, Advisor: Astellas Pharma, Pfizer/Astellas, AstraZeneca, AbbVie, Exelixis, Merck, Amgen, Janssen Oncology, Sanofi, Astellas Pharma, Pfizer; Other, Institutional, Research Funding: AbbVie, Astellas Pharma, Macrogenics, Janssen Oncology, Plexxikon, Harpoon Therapeutics, Merck, Novartis; Financial Interests, Personal, Other, Patent licensed to Corcept Therapeutics: University of Chicago. Y. Lu: Other, Institutional, Research Grant: Lantheus; Other, Personal, Local PI: Lantheus. M. Lilly: Other, Personal, Local PI: Lantheus; Other, Institutional, Research Funding: Lantheus. J. Calais: Other, Personal, Advisory Role: Amgen, Advanced Accelerator Applications, Astellas, Bayer, Blue Earth Diagnostics, Curium Pharma, DS Pharma, Fibrogen, GE Healthcare, Isoray, IBA Radiopharma, Janssen Pharmaceuticals, Monrol, Lightpoint Medical, Lantheus, Novartis, Pfizer, Point Biopharma, Progenics, Radiomedix, Sanofi, Siemens-Varian, SOFIE, Telix Pharmaceuticals; Other, Institutional, Research Grant: Lantheus, Novartis, POINT Biopharma. G. Bratslavsky: Financial Interests, Personal, Other, Salary, stocks and ownership: Avicella; Financial Interests, Personal, Other, Salary and stocks: Aptametrix; Financial Interests, Personal, Ownership Interest: Ilgen, Taurus; Financial Interests, Institutional, Local PI: Ferring Pharmaceuticals, Curium US LLC, QED Therapeutics, Progenics Pharmaceutical, Janssen Research & Development, Astellas, CoImmune; Non-Financial Interests, Leadership Role, Past President: SUO-CTC; Non-Financial Interests, Officer, President-elect: Northeastern Section of AUA; Non-Financial Interests, Leadership Role, Deputy Director: Upstate Cancer Center. M. Vasanawala: Other, Personal, Local PI: Lantheus; Other, Institutional, Research Grant: Lantheus. G.A. Ulaner: Other, Personal, Speaker, Consultant, Advisor: Lantheus, GE Healthcare; Other, Personal, Advisory Board: Precirix, Nuclidium. F. Pouliot: Other, Personal, Speaker, Consultant, Advisor: AbbVie, Advanced Accelator Applications/Novartis, Amgen, Astellas Pharma, AstraZeneca, Bayer, Janssen, Merck, Sanofi, TerSera, Tolmar. D. Laidley: Other, Personal, Advisory Board: Advanced Accelerator Application/Novartis, Bayer, Ipsen; Other, Personal, Local PI: Advanced Accelerator Applications/Novartis, POINT Biopharma, Progenics; Other, Personal, Speaker, Consultant, Advisor: Advanced Accelerator Applications/ Novartis. N. Fleshner: Other, Personal, Local PI: Lantheus; Other, Institutional, Research Grant: Lantheus. F. Saad: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Janssen, Pfizer, Myovant, Novartis, AstraZeneca, Merck; Financial Interests, Institutional, Local PI: Novartis, Astellas, Bayer, Janssen, Sanofi, BMS, Amgen, Pfizer, Merck; Financial Interests, Institutional, Coordinating PI: AstraZeneca. Y. Menda: Other, Institutional, Research Funding: Novartis, Perspective Therapeutics, Fusion Pharmaceuticals, Progenics Pharmaceuticals.