Phase 1 Study of PT199 Begins for the Treatment of Solid Tumors

The first patient was dosed with PT199, the anti-CD73 monoclonal antibody (mAb), for the treatment of multiple advanced tumors. This dose was administered in a phase 1 study (NCT05431270), announced by Phanes Therapeutics, Inc.1

"The CD73 pathway represents a very promising target for addressing the immunosuppressive TME and we are pleased to open this study and bring this potential best-in-class mAb to cancer patients who have few treatment options." said Ming Wang, PhD, MBA, Founder and chief executive officer of Phanes Therapeutics.

This phase 1 trial is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PT199 as a monotherapy and in combination with a PD-1 inhibitor for the treatment of patients with locally advanced or metastatic solid tumors who have progressed after standard therapy. Participants 18 years or older with measurable disease with at least 1 lesion amenable to response assessment per RECIST 1.1 criteria, adequate organ function, and ECOG performances stats of 0 or 1 are eligible for enrollment.

The phase 1 trial has a monotherapy dose escalation part (A), a combination therapy dose escalation part (B), and a combination therapy dose expansion part (A). In part A, the starting PT199 dose is 10 mg/kg weekly and will increase to 20 mg/kg once weekly, 30 mg/kg once weekly, and 30 mg/kg every 3 weeks. Part B will evaluate PT199 at 20 mg/kg weekly and include the PD-1 inhibitor at 200 mg once every 3 weeks. Part C will search for the maximum tolerated dose of the combination therapy.The primary end point of the study is the maximum tolerated dose, and the secondary end points include preliminary efficacy and pharmacodynamics.2

In an abstract presented at the 2022 American Association of Cancer Research Annual Meeting, investigators reported that anti-CD73 therapeutic antibodies have largely subdued clinical activity and unfavorable characteristics, including incomplete enzyme inhibition, know as the “hook effect”, but their research supported on PT199 bound to a unique site on CD73 which bypassed and corrected the clinical flaws with the first generation of anti-CD73 mAbs. PT199 inhibits soluble shed CD73 and membrane-bound CD73 to completion without the “hook effect”. Research showed that PT199 exhibited no clinical observations up to the dose of 300 mg/kg weekly repeated dosing, and it had a very favorable PK profile. These results from a preclinical study support the phase 1 clinical trial.3

References:

1. Phanes therapeutics announces first patient dosed in phase 1 study of PT199 for advanced solid tumors. Press release. PR Newsire; August 23, 2022. Accessed August 24, 2022. https://prn.to/3ckUB5R

2. Dose escalation/expansion study of PT199 (an anti-CD73 mAb) administered alone and in combination with a PD-1 inhibitor. ClinicalTrials.gov. Updated August 12, 2022. Accessed August 24, 2022. https://clinicaltrials.gov/ct2/show/record/NCT05431270?term=NCT05431270&draw=1&rank=1&view=record

3. Jia H, Li J, Pei F, et al. PT199, a next generation anti-CD73 mAb that inhibits both membrane-bound and soluble CD73 activity to completion without “hook effect” [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4259. Accessed August 24, 2022. https://aacrjournals.org/cancerres/article/82/12_Supplement/4259/702856