Updated results from a first-in-human phase 1,2 study of ACE-106, a highly selective and potentially best-in-class PARP1 inhibitor in advanced solid tumors
Presenter: Kuo-Long Yu, PhD Session: First-in-Human Phase I Clinical Trials Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Xingyun Cai 1 , Jian Zhang 2 , Yu Chen 3 , Yanxia Shi 4 , Wei Wang 5 , Zhanhong Chen 6 , Jiongjie Chen 1 1 Acerand Therapeutics (Hong Kong) Limited, Shanghai, China, 2 Fudan University Shanghai Cancer Center, Shanghai, China, Shanghai, China, 3 Fujian Cancer Hospital, Fuzhou, China, 4 Sun Yat-sen University Cancer Center, Guangzhou, China, Guangzhou, China, 5 Shanxi Medical University Second Hospital, Taiyuan, China, Taiyuan, China, 6 Zhejiang Cancer Hospital, Hangzhou, China, Hangzhou, China
Abstract
Background: ACE-106 (ACE-86225106) is a highly selective PARP1 inhibitor designed to improve the therapeutic index relative to first-generation pan-PARP inhibitors. Here, we report the updated data from the first-in-human study (NCT06380660). Method: The study comprises a “3+3” dose escalation module and a backfill module. Patients (pts) with advanced or metastatic solid tumors were treated with ACE-106 monotherapy QD PO. Enrollment in the backfill module required germline or somatic HRR mutations (HRRm), including BRCA1/2, PALB2, or CDK12 mutations, while the dose escalation module allowed pts without HRRm. The primary objective was safety; secondary objectives were PK, pharmacodynamics, and preliminary efficacy. Result: As data cut-off (Dec 31, 2025), 52 pts received ACE-106 at dose levels ranging from 5-80 mg, with a median treatment duration of 2.1 (range 0.6-18.4) months. The pts had a median 4 (range 1-12) lines of prior systemic therapy, and 29% had prior PARPi. ACE-106 was well tolerated across all dose levels, with no dose-limiting toxicities or grade 4-5 treatment-related adverse events (TRAEs). No TRAEs leading to dose reduction or discontinuation were reported. Grade 3 TRAEs occurred in 17% of pts, with the most common being anemia (10%), decreased platelet count (2%), decreased lymphocyte count (2%), decreased appetite (2%), and vomiting (2%). Hematological toxicity did not increase along with the dose level. Among 16 pts with HRRm evaluable for radiological response per RECIST1.1 criteria, objective response rate (ORR) was 38% (6/16) with the longest duration of response of 12 months; and disease control rate (DCR) was 75% (12/16). Notably, among metastatic castration-resistant prostate cancer (mCRPC) pts with HRRm, ORR was 50% (4/8) and PSA50 response rate was 42% (5/12). One mCRPC pt without HRRm also had a confirmed partial response. Among advanced ovarian cancer (OC) pts who were naïve to pan-PARPi, ORR was 67% (2/3) and DCR was 100%. ACE-106 demonstrated a flat PK curve (Cmax was 1.4-2.3 fold of Cmin) across all 6 doses, with a mean T 1/2 of 20.6-34.5 hours supporting QD dosing. Drug exposure increased proportionally with dose, and up to 69 fold of Cmin to target effective concentration (TEC) ratio was observed at 80mg QD. Conclusion: ACE-106 was well tolerated and showed promising efficacy and excellent PK properties in heavily pre-treated advanced solid tumors. The clinical profile suggests a best-in-class selective PARP1i potential to replace pan-PARPi and justify further development of ACE-106-based combination therapy. Disclosure: This abstract used generative AI to help revise content written by authors.
Disclosure
X. Cai, Acerand Therapeutics (Hong Kong) Limited Employment. J. Zhang, None.. Y. Chen, None.. Y. Shi, None.. W. Wang, None.. Z. Chen, None. J. Chen, Acerand Therapeutics (Hong Kong) Limited Employment.
Cited in
Control: 10592 · Presentation Id: 12082 · Meeting 21436