Ambrx Biopharma reports safety, efficacy data from Phase 1/2 APEX-01 trial

Ambrx Biopharma announced that two abstracts detailing updated safety and efficacy data from the ongoing Phase 1/2 trial, APEX-01, evaluating ARX517 for metastatic castration-resistant prostate cancer were made available as part of the 2023 European Society of Medical Oncology Congress 2023 meeting, taking place in Madrid, Spain, October 20-24, 2023. APEX-01 opened for enrollment in July 2021, and is the only ongoing clinical trial in the United States targeting PSMA with an antibody-drug conjugate. APEX-01 is a first-in-human, open-label, dose escalation and dose expansion study enrolling patients with mCRPC whose tumors have progressed on at least two prior FDA-approved treatments, including at least one second-generation androgen receptor pathway inhibitor. The inclusion criteria included one of the following: PSA progression defined by a minimum of two rising PSA values, radiographic progression by RECIST v1.1 or disease progression by the presence of new bone lesions. The two clinical abstracts submitted to ESMO regarding the APEX-01 trial used a cutoff date of May 3, 2023. Ambrx will provide more mature data with a later data cutoff date, including a significantly greater number of patients from the dose expansion portion of APEX-01, in the ESMO posters and in its associated press release. Title: APEX-01: First-in-human Phase 1/2 study of ARX517, an anti-prostate-specific membrane antigen antibody-drug conjugate, in patients with metastatic castration-resistant prostate cancer: Abstract Highlights: In dose escalation patients treated via intravenous infusion every 3 weeks at putative therapeutic doses greater than or equal to2.0 mg/kg: 7 out of 9 patients experienced a greater than or equal to50% PSA reduction; 3 out of 3 patients in Cohort 6; 2 out of 3 patients in Cohort 7; 2 out of 3 patients in Cohort 8; 5 out of 5 patients experienced a greater than or equal to50% ctDNA reduction; 3 out of 3 patients in Cohorts 6; 2 out of 2 patients in Cohort 7; Cohort 8 data not available; In 24 dose escalation patients treated from 0.32 mg/kg to 2.88 mg/kg ARX517 was well-tolerated at all doses; No treatment-related SAEs observed; No DLTs observed; Four Grade 3 treatment-related adverse events were reported in Cohort 5, Cohort 7 and Cohort 8. Title: ARX517, a next generation anti-PSMA antibody drug conjugate, demonstrates notable stability and pharmacokinetic profile in the ARX517 Phase 1/2 clinical trial. Abstract Highlights: The pharmacokinetics population consisted of 21 dose escalation patients having received ARX517 across all dose levels; ARX517 exhibited virtually overlapping total antibody and ADC PK concentration-time curves at all dose levels tested indicating strong stability of the ADC with minimal premature payload release; A long ADC terminal half-life of ~6-10 days was observed at doses greater than or equal to 1.4 mg/kg, thereby maximizing drug exposure over a dosing cycle of 3 weeks; Low concentrations of pAF-AS269 were observed at all dose levels and appeared slowly in the circulation, with Cmax observed approximately 7 days after administration