Newly published abstract regarding dose escalation patients provides key updates including:
- ≥50% PSA reduction observed across putative therapeutic dose levels ≥2.0 mg/kg – 3 of 3 in Cohort 6 (2.0 mg/kg), 2 of 3 in Cohort 7 (2.4 mg/kg) and 2 of 3 in Cohort 8 (2.88 mg/kg)
- No drug-related severe adverse events (SAEs) and no dose limiting toxicities (DLTs) observed in any cohort
- Pharmacokinetic (PK) data indicated strong ADC stability preventing premature release of anticancer payload
Ambrx to host a live event / webcast to discuss additional data presented at ESMO onSunday, October 22, 2023 , at8 p.m. CEST /2 p.m. ET
APEX-01 opened for enrollment in
The two clinical abstracts submitted to ESMO regarding the APEX-01 trial used a cutoff date of
Title: APEX-01: First-in-human Phase 1/2 study of ARX517, an anti-prostate-specific membrane antigen (PSMA) antibody-drug conjugate (ADC), in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Abstract Highlights:
- In dose escalation patients treated via intravenous infusion every 3 weeks at putative therapeutic doses ≥2.0 mg/kg (Cohort 6 at 2.0 mg/kg, Cohort 7 at 2.4 mg/kg and Cohort 8 at 2.88 mg/kg):
- 7 out of 9 patients experienced a ≥50% 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 ≥50% ctDNA reduction
- 3 out of 3 patients in Cohorts 6
- 2 out of 2 patients in Cohort 7
- Cohort 8 data not available
- 7 out of 9 patients experienced a ≥50% PSA reduction
- In 24 dose escalation patients treated from 0.32 mg/kg (Cohort 1) to 2.88 mg/kg (Cohort 8) ARX517 was well-tolerated at all doses
- No treatment-related SAEs observed
- No DLTs observed
- Four Grade 3 treatment-related adverse events (TRAEs) were reported in Cohort 5 (1.7 mg/kg), Cohort 7 (2.4 mg/kg) and Cohort 8 (2.88 mg/kg) (two cases of lymphopenia, two cases of platelet count decrease)
Title: ARX517, a next generation anti-PSMA antibody drug conjugate (ADC), demonstrates notable stability and pharmacokinetic (PK) profile in the ARX517 Phase 1/2 clinical trial (APEX-01)
Abstract Highlights:
- The pharmacokinetics population consisted of 21 dose escalation patients having received ARX517 across all dose levels (0.32 to 2.4 mg/kg):
- 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 ≥ 1.4 mg/kg, thereby maximizing drug exposure over a dosing cycle of 3 weeks
- Low concentrations of pAF-AS269 (approximately 0.02–0.2 ng/mL) were observed at all dose levels and appeared slowly in the circulation, with Cmax observed approximately 7 days after administration
“Based on the encouraging preliminary efficacy and safety results observed in the APEX-01 trial, we believe ARX517 has the potential to overcome the instability and resulting toxicity challenges of previous PSMA-targeted ADCs and may hold promise as a novel treatment modality for patients with mCRPC,” said Daniel J. O’Connor, Chief Executive Officer of Ambrx. “We look forward to sharing more results from the trial at the ESMO conference, which will include additional data from dose expansion cohorts.”
The full abstracts are available on the Company’s website via thislink.
Details of the poster presentations are as follows:
Session Title: Prostate Cancer Poster Session
Title: APEX-01: First-in-human phase 1/2 study of ARX517, an anti- prostate-specific membrane antigen (PSMA) antibody-drug conjugate (ADC), in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Presenting Author: John Shen, M.D.
Date/Time: Sunday, October 22, 2023, from 12:00 –
Session Title: Prostate Cancer Poster Session
Title: ARX517, a next generation anti-PSMA antibody drug conjugate (ADC), demonstrates notable stability and pharmacokinetic (PK) profile in the ARX517 phase 1 clinical trial (APEX-01)
Presenting Author: Scott
Date/Time: Sunday, October 22, 2023, from 12:00 –
Session Title: Basic Science Poster Session
Title: Evaluation of ARX517, a next-generation anti-PSMA antibody drug conjugate for prostate cancer treatment, in preclinical enzalutamide-resistant and enzalutamide-sensitive pharmacology models and in toxicology models
Presenting Author: Shawn Zhang, Ph.D.,
Date/Time: Sunday, October 22, 2023, from 12:00 –
Session Title: Basic Science Poster Session
Title: Preclinical characterization of ARX305, a next-generation anti-CD70 antibody drug conjugate for the treatment of CD70-expressing cancers
Presenting Author: David Mills, Ph.D.,
Date/Time: Sunday, October 22, 2023, from 12:00 –
Ambrx APEX-01 ARX517 Webcast Information
Click here to register and attend Ambrx’s KOL Event discussing additional ARX517 data presented at ESMO and showcasing presentations from prostate cancer experts, or visit www.ambrx.com.
About ARX517
ARX517 is an investigational antibody-drug conjugate composed of a humanized anti-PSMA mAb linked to AS269, an
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,
ARX517 has the potential to be a first- and best-in-class anti-PSMA ADC addressing the high unmet medical need in mCRPC.
About APEX-01
About
Forward-Looking Statements
This press release includes certain “forward-looking statements” intended to qualify for the “safe harbor” from liability established by the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements may be identified by the words “intend,” “plan,” and similar expressions. Forward-looking statements are based on Ambrx’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, those risks and uncertainties associated with: Ambrx’s ability to execute on its strategy including with respect to the timing of its R&D efforts, initiation of clinical trials and other anticipated milestones; risks associated with development and marketing approval of novel therapeutics, including potential delays in clinical trials and regulatory submissions and the fact that future clinical trial results/data may not be consistent with interim, initial or preliminary results/data or results/data from prior preclinical studies or clinical trials; Ambrx’s ability to fund operations as anticipated; and the additional risks and uncertainties set forth more fully under the caption “Risk Factors” in Ambrx’s Current Report on Form 8-K filed with the
Contacts
INVESTORS
617-308-4306
mmoyer@lifesciadvisors.com
MEDIA
615-651-4622
media@ambrx.com
Source:
Source:
2023 GlobeNewswire, Inc., source