Cohort 9
Following completion of the 21-day observation period at 3.4 mg/kg (Cohort 9), no dose limiting toxicities (DLTs) or serious adverse events (SAEs) were observed
Two patients in Cohort 9 experienced rapid PSA reduction at three weeks post-treatment following the first ARX517 dose
Cohort 8
The cohort (2.88 mg/kg) is now fully enrolled with 20 patients
Recommended phase 2 dose expected by early next year
Ambrx Biopharma, Inc., or Ambrx (NASDAQ: AMAM), today announced a clinical update regarding its proprietary anti-PSMA antibody drug conjugate (ADC) ARX517 in the ongoing APEX-01 Phase 1 / 2 dose escalation and dose expansion clinical trial in metastatic castration-resistant prostate cancer (mCRPC).
Following the completion of the 21-day DLT observation period from APEX-01 dose escalation Cohort 9 (3.4 mg/kg), no DLTs or SAEs were observed. Two of the three patients in Cohort 9 had a rapid PSA reduction of 91% and 33% at the first PSA assessment at three weeks post-treatment and following only one dose of ARX517. A PSA decrease was not reported in the third patient because the patient had non-PSA secreting mCRPC. On Monday November 27, the safety monitoring committee (SMC) voted to dose escalate to 4.5 mg/kg (Cohort 10) as well as expand patients at the 3.4 mg/kg dose (Cohort 9). All expansion cohorts, Cohort 4 (1.4 mg/kg at n=23), Cohort 6 (2.0 mg/kg at n=23), and Cohort 8 (2.88 mg/kg at n=20) are now fully enrolled.
“We continue to observe no DLTs or SAEs at the highest ARX517 dose tested. We believe this is a direct result of the stability of conjugation supported by PK data presented at ESMO last month. While we are opportunely positioned to explore higher doses, we have already observed significant PSA50 decline and long duration on treatment at 2.0 mg/kg,” said Sandra Aung, Ph.D., Chief Clinical Officer of Ambrx. “The high interest in our PSMA-targeting ADC and pace of enrollment in the APEX-01 study has been outstanding and based on this we are anticipating to reach a recommended phase 2 dose by early next year.”
ARX517 is an investigational antibody-drug conjugate composed of a humanized anti-PSMA mAb linked to AS269, an Ambrx proprietary potent microtubule inhibitor. ARX517 is designed to target the prostate-specific membrane antigen (PSMA). PSMA is highly expressed in metastatic castration-resistant prostate cancer (mCRPC) and has been validated as a therapeutic target.
In preclinical studies, the cancer cell killing payload of ARX517, pAF-AS269, is highly cytotoxic when delivered by a mAb into cancer cells. ARX517’s site-specific linkage, stable conjugation chemistry, and non-cleavable linker result in an ADC with a homogenous drug-antibody-ratio, mAb-like biophysical properties, and exceptional stability. Therefore, Ambrx believes ARX517 can promote highly specific tumor cell killing with minimal off-target toxicity.
ARX517 has the potential to be a first- and best-in-class anti-PSMA ADC addressing the high unmet medical need in mCRPC.
Ambrx is currently investigating ARX517 in the APEX-01 (NCT04662580) first-in-human Phase 1 / 2, multicenter, dose escalation and dose expansion clinical study to evaluate the safety, pharmacokinetics, and preliminary anti-tumor activity of ARX517 in adult subjects and is currently enrolling patients with advanced prostate cancer (mCRPC) whose tumors have progressed following at least two FDA approved treatments for prostate cancer, including at least one second-generation androgen receptor pathway inhibitor, and have met one of the following three criteria: PSA progression defined by a minimum of two rising PSA values or radiographic progression by RECIST v 1.1 or disease progression by the presence of new bone lesions.
Ambrx is a clinical-stage biopharmaceutical company using an expanded genetic code technology platform to discover and develop next-generation antibody drug conjugates (ADCs) and other engineered therapies to modulate the immune system. Ambrx is advancing a focused portfolio of clinical and preclinical programs designed to optimize efficacy and safety in multiple cancer indications, including ARX517, its proprietary ADC targeting the prostate-specific membrane antigen (PSMA) and ARX788, its proprietary ADC targeting HER2. In addition, Ambrx has preclinical and clinical collaborations with multiple partners on drug candidates generated using Ambrx technology. Ambrx was spun out of The Scripps Research Institute in 2003 and has several other product candidates utilizing ADCs and other aspects of Ambrx’s protein engineering technology. For more information, please visit www.ambrx.com. Ambrx routinely posts information that may be important to investors on its website.
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