ESMO 2023: 1804P
As of the data cutoff date in September 2023, the results from the study show that increasing doses of ARX517 led to significant reductions in prostate-specific antigen (PSA). Notably, the deeper reductions in PSA were observed as the dosage levels increased, indicating a dose-dependent response. For instance, a 50% or greater reduction in PSA was observed in 25% of patients in Cohort 4 (1.4 mg/kg) and 50% of patients in Cohort 6 (2.0 mg/kg). Additionally, a remarkable 90% or greater PSA reduction was seen in 6% of patients in Cohort 4 and 36% of patients in Cohort 6.
The data also highlights the efficacy of ARX517, particularly in Cohorts 6-8, where multiple efficacy endpoints consistently demonstrated promising anti-cancer activity. This includes a 52% PSA reduction in 12 out of 23 patients and a 50% or greater ctDNA reduction in 17 out of 21 patients. Furthermore, 50% of patients experienced a greater than 30% reduction in target lesion(s), including liver and lung lesions.
In terms of safety, ARX517 displayed a strong and unique safety profile among heavily treated late-stage metastatic castration-resistant prostate cancer (mCRPC) patients. No severe treatment-related adverse events (SAEs) or dose-limiting toxicities (DLTs) were observed, and the drug-related discontinuation rate was low at 3%. Grade 3 treatment-related adverse events (TRAEs) were reported in only 9.2% of patients across all cohorts, with a higher frequency observed at doses of 2.0-2.88 mg/kg. Notably, there were no Grade 4 or 5 treatment-related adverse events. The incidence of Grade 1 or 2 TRAEs was relatively low, with common events including dry mouth (24%), dry eye (22%), and fatigue (20%).
The ongoing Phase 1 trial included a representative patient population of late-stage mCRPC, with patients having received multiple prior therapies, including second-generation androgen receptor pathway inhibitors (ARPIs), taxanes, immunotherapy, and PSMA-targeted radionuclide therapy. Importantly, the study showed positive PSA reductions even in patients who had prior PSMA-targeted radionuclide therapy.
The pharmacokinetics (PK) data indicated strong stability of ARX517 as an antibody-drug conjugate (ADC). The data showed minimal premature release of the cytotoxic payload, maximizing its delivery to PSMA-expressing cancer cells. Additionally, the long ADC terminal half-life supports consistent pressure on PSMA-expressing cancer cells and allows for longer dosing intervals.
As of the data cutoff date in September 2023, dose escalation is ongoing, with Cohort 8 (2.88 mg/kg) expansion and Cohort 9 (3.4 mg/kg) escalation in progress.
Ambrx has successfully secured additional funding, fortifying its financial position and ensuring runway extension until 2026. In a notably challenging market environment, Ambrx managed to secure $75 million in a recent funding round conducted in June, building on a prior $78 million raise in March. These financial achievements reflect the company’s resilience and determination to navigate the competitive landscape of the biopharmaceutical industry.
