Ambrx Biopharma announces data from Phase 1/2 APEX-01 study of ARX517

Ambrx Biopharma announced that in biomarker unselected patients ARX517 monotherapy demonstrated a strong antibody-drug conjugate safety profile at all doses tested with promising early efficacy signals that included PSA50 declines, ctDNA reductions, and RECIST v1.1 tumor response. The two primary objective of APEX-01 are to analyze the safety and tolerability of ARX517 and establish a recommended Phase 2 dose. Data Highlights: As of the data cutoff date, highlights from the safety and efficacy data are summarized below: Deep PSA reductions have been seen with increasing ARX517 dose. PSA reductions deepened as dose levels increased, demonstrating a dose dependent PSA reduction: greater than or equal to50% PSA reduction observed in 25% and 50% of patients at 1.4 mg/kg and 2.0 mg/kg, respectively; greater than or equal to90% PSA reduction observed in 6% and 36% of patients at 1.4 mg/kg and 2.0 mg/kg, respectively; Multiple coinciding efficacy endpoints demonstrate a consistent and promising anti-cancer activity at therapeutic doses of 2.0 – 2.88 mg/kg: 52% patients experienced a greater than or equal to50% PSA reduction; 7 of 14 patients at 2.0 mg/kg; 3 of 6 patients at 2.4 mg/kg; 2 of 3 patients at 2.88 mg/kg; 81% patients experienced a greater than or equal to50% ctDNA reduction; 50% experienced a greater than30% reduction in target lesion, one of which had a reduction in liver and lung lesions. ARX517 demonstrates a strong and differentiated safety profile in heavily pretreated late stage mCRPC patients: No treatment-related SAEs or DLTs were observed; Low drug related discontinuation rate 3%; Grade 3 TRAEs were reported in only 9.2% patients across all cohorts, and only 13% at doses 2.0-2.88 mg/kg; Three patients with lymphopenia, two patients with transient platelet count decrease, and one patient with asymptomatic left ventricular dysfunction that was not deemed serious; No Grade 4 or 5 treatment-related adverse events were reported; Low frequency of Grade 1 or 2 TRAEs, including dry mouth, dry eye and fatigue. Ongoing first-in-human Phase 1 trial enrolled 65 patients who exhausted approved life-extending treatments is representative of late line mCRPC patient population: Median 4 with a maximum of 13 prior therapies; 100% received at least one 2nd generation ARPI, 48% of patients received both enzalutamide and abiraterone; 66% of patients received at least one prior taxane, 46% of patients received at least one prior immunotherapy and 17% of patients received at least one prior PSMA-targeted radionuclide therapy. PSA reductions observed in patients who had prior PSMA-targeted radionuclide therapy: 50% of patients treated with a PSMA TRT experienced a greater than or equal to50% PSA reduction at therapeutic doses of 2.0 – 2.88 mg/kg; Deepening PSA response with dose escalation combined with not seeing SAEs and DLTs support continuing dose escalation to higher levels.