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Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.

An open label phase 1/2A study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of TRC253, an androgen receptor antagonist, in patients with metastatic castration-resistant prostate cancer.

Advanced Disease

Genitourinary (Prostate) Cancer

2019 ASCO Annual Meeting

Abstract No:

J Clin Oncol 37, 2019 (suppl; abstr e16542)

Author(s): Dana E. Rathkopf, Mansoor N. Saleh, Frank Yung-Chin Tsai, Mehmet Asim Bilen, Lee S. Rosen, Marco Gottardis, Jeffrey R. Infante, Bonne J. Adams, Lilian Liu, Charles P. Theuer, James L. Freddo, Neeraj Agarwal; Memorial Sloan Kettering Cancer Center, New York, NY; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; HonorHealth Research Institute, Scottsdale, AZ; Winship Cancer Institute of Emory University, Atlanta, GA; University of California Los Angeles, Los Angeles, CA; Janssen Research and Development, Spring House, PA; TRACON Pharmaceuticals, Inc., San Diego, CA; Tracon Pharmaceuticals, San Diego, CA; University of Utah Huntsman Cancer Institute, Salt Lake City, UT

Abstract Disclosures


Background: TRC253 is a high-affinity, orally active small molecule antagonist of the androgen receptor (AR) and specific mutated variants of AR that does not possess agonist activity towards either wild type or mutated AR. TRC253 inhibits AR nuclear translocation as well as AR binding to DNA and is a transcription antagonist. TRC253 treatment is efficacious in an LNCaP xenograft model driven by F877L mutant AR. Methods: In P1 dose escalation, pts with mCRPC previously treated with an AR inhibitor were assigned to increasing TRC253 doses of 40-320 mg daily. Dose escalation followed single-pt dose escalation design for the 40, 80 mg cohorts and expanded to 3+3 design in the 160, 240, 280, and 320 mg cohorts to assess safety, determine the recommended phase 2 dose (RP2D), and evaluate prostate-specific antigen response at week 12. Toxicity and efficacy assessments used NCI-CTCAE v4.03 and PCWG3 criteria, respectively. Pts were centrally screened by circulating tumor DNA using the BEAMing digital PCR assay. Results: Twenty-two pts were enrolled in phase 1 at TRC253 doses of 40 (n = 1), 80 (n = 1), 160 (n = 2), 240 (n = 6), 280 (n = 4), and 320 mg (n = 8) daily in 28-day cycles. One DLT of G3 QTcF prolongation occurred at 320 mg. No drug-related SAEs were reported. Drug-related AEs ≥ G2 included QTcF prolongation (2 G2, 2 G3), elevated lipase (1 G3), fatigue (4 G2), arthralgia (1 G2), diarrhea (1 G2), and platelet count decrease (1 G2). One pt on study had AR F877L at baseline and remained on treatment for 49 wks with PR by RECIST. The remaining 21 pts did not have AR F877L at baseline and of these, 48% (10) remained on study > 6 cycles and one pts had a > 50% decrease in PSA. Target PK exposures were achieved consistently at 280 mg. 280 mg was selected as the RP2D based on safety and PK data. Conclusions: TRC253 daily at 280 mg was well-tolerated and selected as the RP2D. P2 dose expansion is currently enrolling 2 cohorts: 15 pts with AR F877L and 30 pts without AR F877L. The objectives of P2 include collection of additional data for safety, PK, PET and efficacy of TRC253 in mCRPC pts with specific AR mutations. Clinical trial information: NCT02987829

Other Abstracts in this Sub-Category:


1. Overall survival (OS) results of a phase III randomized trial of standard-of-care therapy with or without enzalutamide for metastatic hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led international cooperative group trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: LBA2 First Author: Christopher Sweeney
Category: Genitourinary (Prostate) Cancer - Advanced Disease


2. Impact of darolutamide (DARO) on pain and quality of life (QoL) in patients (Pts) with nonmetastatic castrate-resistant prostate cancer (nmCRPC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 5000 First Author: Karim Fizazi
Category: Genitourinary (Prostate) Cancer - Advanced Disease


3. Interest of short hormonotherapy (HT) associated with radiotherapy (RT) as salvage treatment for metastatic free survival (MFS) after radical prostatectomy (RP): Update at 9 years of the GETUG-AFU 16 phase III randomized trial (NCT00423475).

Meeting: 2019 ASCO Annual Meeting Abstract No: 5001 First Author: Christian Carrie
Category: Genitourinary (Prostate) Cancer - Advanced Disease