Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancers, but not in most non-prostate normal tissues, making it a potential therapeutic target. EC1169, a PSMA-targeted conjugate of the microtubule inhibitor tubulysin B hydrazide is being studied in a two-part phase 1 dose escalation (A)/expansion (B) study in mCRPC. The utility of the PSMA-targeted companion imaging agent 99mTc-EC0652 is also being evaluated as a patient selection tool. Part A has been completed. We now report the part B data on pts treated to date.
EC1169 is administered as an IV bolus on days 1, 8 every 21 days. The RP2 dose of 6.5 mg/m2 was determined in Part A. Part B pts are treated at the RP2 dose and enrolled in 1 of 2 cohorts: mCRPC taxane naïve (cohort 1, 45 pts) or taxane exposed (cohort 2, 40 pts). Prior to treatment, pts undergo a 99mTc-EC0652 SPECT/CT scan. The primary endpoint of Part B is median radiographic progression-free survival (rPFS). Other study evaluations are OS, PSA, and CTC-based biomarkers.
Thirty-four of a planned 85 pts in Part B have been treated (14 taxane naïve, 20 taxane exposed). Median age is 70 (range: 49-84). Median number of cycles is 3 (range: 1-7). Twenty-six pts (76.5%) reported at least 1 treatment related AE. Most treatment related AEs (TRAEs) are Gr1 and 2; G3 treatment-related constipation occurred in 1 pt. No Grade 4 TRAEs have been reported. No dose reductions due to AEs have occurred. Six of twelve evaluable taxane-exposed pts in Part B had stable disease or better at their first post-baseline scan (9 wks). One pt currently beyond the 18-week scan has achieved durable resolution of his soft tissue disease. Imaging with 99mTc-EC0652 suggests excellent disease localization.
The RP2 dose of EC1169 is 6.5 mg/m2 (D1, 8 every 21 days). EC1169 has been well tolerated in 34 Part B pts at the RP2 dose A PSMA-targeted therapeutic strategy appears viable. There is evidence of anti-tumor activity in both the taxane naïve and taxane exposed pts.
Clinical trial identification
Legal entity responsible for the study
A. Armour, M. Groaning: Employee of Endocyte, owns company stock. R. Messmann: Contractor for Endocyte, owns company stock. All other authors have declared no conflicts of interest.