In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 5038-5038
Abstract:
5038 Background: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancers, but not in most normal tissues, making it a potential therapeutic target. We are conducting a two-part phase 1 dose escalation/expansion study of EC1169, a PSMA-targeted conjugate of the microtubule inhibitor tubulysin B hydrazide in mCRPC. The utility of the PSMA-targeted companion imaging agent 99m Tc-EC0652 is also being evaluated as a patient selection tool. The safety, efficacy, and imaging-based PSMA selection strategy are being investigated in Part A (dose escalation) and Part B (2-stage, 2-cohort expansion). Methods: Part A pts were eligible if they progressed on abiraterone or enzalutamide, and were treated with a taxane. EC1169 was administered as an IV bolus on days 1, 8 every 21 days. Part B pts are enrolled in 1 of 2 cohorts, mCRPC taxane naïve (cohort 1, 45 pts) and taxane exposed (cohort 2, 40 pts). Prior to treatment, pts undergo a 99m Tc-EC0652 SPECT scan. The primary endpoint of Part B is median radiographic progression-free survival (rPFS). Other study evaluations are OS, PSA, and CTC-based biomarkers. Results: Part A is now complete: the RP2 dose is 6.5 mg/m 2 , on the basis of non-DLT transaminitis. 20 Part A/B pts have been treated at the RP2 dose (7 taxane naïve, 13 taxane exposed). Median age is 69 (range: 59-82). Median number of cycles is 2 (range: 1-7). 10 pts (50%) reported at least 1 treatment related AE. Most treatment related AEs are Gr1 and 2; G3 thrombocytopenia, fatigue, and constipation have occurred in 1 pt each. No Grade 4 treatment related AEs have been reported. No DLT or toxicity requiring dose reductions occurred. Four taxane-exposed pts in Part B have reached their first 9 wk radiographic assessment, of which two have soft tissue disease. One of those two patients (50%) has achieved an unconfirmed RECIST PR. Conclusions: The RP2 dose of EC1169 is 6.5 mg/m 2 . EC1169 has been well tolerated in 20 pts at the RP2 dose. Imaging with 99m Tc-EC0652 suggests excellent disease localization supporting a PSMA-targeted therapeutic strategy. There is evidence of anti-tumor activity in both the dose escalation and expansion cohorts. Clinical trial information: NCT02202447.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.5038
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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