3095 Background: GRPR is overexpressed in many solid tumors. NeoB binds to GRPR with high affinity and can be radiolabeled for theranostics. NeoRay is the first-in-human study of 177 Lu-NeoB in pts with advanced solid tumors overexpressing GRPR. Phase (Ph) I reported favorable organ dosimetry and safety, and a recommended Ph II dosage (RP2D) of 9.25 GBq. Here, we report the Ph IIa primary analysis. Methods: This Ph IIa, open-label, multicenter, dosage expansion study enrolled 5 adult cohorts with confirmed 68 GaGa-NeoB tumor uptake: A) HR+/HER2- breast cancer; B) prostate cancer (PCa); C) gastrointestinal stromal tumor (GIST); D) impaired renal function; and E) pts eligible for Cohorts A–C who also received sacubitril/valsartan (49/51 mg) at Cycle 1 to assess drug-drug interaction (DDI). There was no formal sample size calculation; the target was ~12 pts in Cohorts A–C, ≤6 pts in D, and ~3 pts in E. 177 Lu-NeoB 9.25 GBq was to be administered every 6 wks for ≤9 cycles, except in DDI Cohort E (5.55 GBq in Cycle 1, then 9.25 GBq). Primary endpoints (descriptive statistics) were individual response (centrally assessed by RECIST v1.1) in Cohorts A–C, and 177 Lu-NeoB PK and dosimetry in Cohort E. Secondary endpoints included safety/tolerability and QoL. Results: Overall, 18 pts (A n = 4; B n = 7; C n = 2; D n = 2; E n = 3) received treatment (median age 65 y; 56% male). Median (range) 177 Lu-NeoB exposure was 9 (6–60) wks; median (range) cumulative activity administered was 12.1 (5.7–81.4) GBq. At data cutoff (7 Jan 2025), 4 pts (B n = 2; C n = 2) had completed treatment (≥3 cycles); 1 pt (GIST) received 9 cycles. Of 10 pts with centrally assessed post-baseline response data, 1 had partial response (PCa), 5 had stable disease (of whom 2 had stable disease ≥20 wks GIST), and 4 had progressive disease. Adverse events (AEs) occurred in 17 (94%) pts (serious AEs in 3 17% pts; Gr ≥3 AEs in 6 33% pts). Treatment-related AEs (TRAEs) occurred in 7 (39%) pts (all non-serious; Gr ≥3 in 2 11% pts). The most common TRAEs were fatigue (n = 5, 28%), anemia (n = 2, 11% Gr ≥3 in 1 pt, 6%), and bone pain (n = 2, 11%). One pt died of hepatic failure related to disease progression (not a TRAE). No AEs led to dosage reductions/interruptions/discontinuations. Dosimetry evaluated in 12 pts showed favorable biodistribution, similar to Ph I. Projected cumulative absorbed doses in target organs were below EBRT limits; lesion absorbed doses were generally consistent across cohorts. Mean ± SD EORTC QLQ-C30 global health scores in Cohorts A–C were 70 ± 22 at baseline (n = 12) and 73 ± 16 at Cycle 2 (n = 4), suggesting stable QoL. Conclusions: NeoRay Ph IIa data at the 177 Lu-NeoB RP2D (9.25 GBq) reinforce Ph I dosimetry and safety results and support further clinical evaluation. Most AEs were mild/moderate and no new safety signals were identified. Despite the limited sample size, preliminary signs of antitumor activity were observed. Clinical trial information: NCT03872778 .
Mittra, et al. (Wed,) studied this question.