This is the COSA abstract: 177Lu-PSMA-617 as monotherapy or in...

This is the COSA abstract:

¹⁷⁷Lu-PSMA-617 as monotherapy or in combination with NOX66 for the treatment of men with late-stage metastatic castrate resistant prostate cancer (mCRPC): An exploratory analysis. (#177)
Luke Ardolino ¹  ,  Reuben Tang ²  ,  Sarennya Pathmanandavel ¹  ,  Megan Crumbaker ^{1 3 4}  ,  Anthony Joshua ^{1 4}  ,  Louise Emmett ^{2 4}

1. The Kinghorn Cancer Centre, St. Vincent’s Hospital, Sydney, NSW, Australia
2. Department of Nuclear Medicine and Theranostics, St Vincent's Hospital, Sydney, NSW, Australia
3. Garvan Institute of Medical Research, Sydney, NSW, Australia
4. St. Vincent’s Clinical School, UNSW, Sydney, NSW, Australia

Aims: ¹⁷⁷Lu-PSMA-617 is an emerging targeted therapy that has shown good efficacy and safety in mCRPC. Idronoxil is an inhibitor of external NADH oxidase type 2 that possesses downstream pro-apoptotic actions that confer radio-sensitivity to cancer cells. We aimed to evaluate the efficacy of ¹⁷⁷Lu-PSMA-617 monotherapy versus combination ¹⁷⁷Lu-PSMA-617/NOX-66 (Veyondra) therapy.
Methods: 30 men with progressive mCRPC despite docetaxel, cabazitaxel and either abiraterone or enzalutamide were enrolled across two therapeutic studies. The first with¹⁷⁷Lu-PSMA-617 alone (14 men) and the second ¹⁷⁷Lu-PSMA-617 + NOX66 (16 men; 8 receiving 400mg and 8 receiving 800mg daily for 10 days per cycle). Both studies required PSMA uptake on PSMA PET of greater than liver activity with no discordant disease compared with FDG-PET. Each man received ¹⁷⁷Lu-PSMA-617 at 6-weekly intervals.
Results: Baseline PSA distributions were similar in the combination and monotherapy trials (median PSA level 147ng/mL [IQR 67-443] versus 88ng/mL [IQR 54-293] respectively). Significantly more patients in the combination trial initiated a fourth treatment cycle compared to the monotherapy trial (69% vs 21%; P < 0.001). PFS was significantly longer in the combination group 8.4 months (IQR 3.6-10.9) versus the monotherapy group 2 months (IQR 0.2-5.0; mean PSA PFS 7.8 vs 3.4 months [p=0.023]).  A PSA reduction of ≥50% occurred in 69% (11/16) versus 36% (5/14) of patients treated with combination and monotherapy respectively (P=0.073). Kaplan-Meier survival estimation revealed a significant benefit to combination therapy (p=0.014). Cox regression further revealed that combination treatment and increasing SUVmax were significant predictors of PSA PFS (HR 0.239 [95%CI 0.92-0.623] and HR 0.945 [95%CI 0.93-0.977] respectively). No significant treatment related adverse effects were reported in either study.
Conclusions: Within the limits of a comparison of two separate phase 1 trials, the efficacy of PSMA targeted treatments may be significantly improved through patient selection and use of combination treatments.​

These were ALL stage IV patients, similar to those currently being treated by Novartis/Endocyte in their Phase 3 registration trial.  If anything, the Veyonda group was sicker than the monotherapy group, with higher PSA levels.

This is a fabulous result for Veyonda.