1028P - Preliminary phase I results from a first-in-human study of EMB-02, a PD-1xLAG-3 bispecific antibody, in patients (pts) with advanced solid tumors

Background

Co-inhibition of LAG-3 and PD-1 pathways has been shown to yield better efficacy than PD-1 blockade alone in pts with previously untreated metastatic melanoma. EMB-02 is a tetravalent PD-1×LAG-3 bispecific antibody developed based on EpimAb Biotherapeutics’ proprietary Fabs-In-Tandem-Immunoglobulin (FIT-Ig®) platform. In preclinical studies, EMB-02 demonstrated the ability to concomitantly or independently engage immune cells expressing PD-1 and LAG-3 to restore T cell effector function, and induced transient co-degradation of PD-1 and LAG-3 which led to more efficient PD-1 depletion on activated T cells.

Methods

EMB02x101 is an open-label, first-in-human, phase I/II study of EMB-02 in pts with advanced solid tumors. The phase I dose escalation portion evaluated 6-900mg doses of EMB-02 (weekly i.v.), guided by the Bayesian optimal interval (BOIN) design. The primary objectives were to investigate safety and tolerability and determine the MTD and/or the RP2D(s). Secondary objectives included pharmacokinetics (PK), immunogenicity, and preliminary anti-tumor activity.

Results

As of January 31, 2023, EMB-02 was administered to 47 pts during the dose escalation portion (45% had ≥3 prior lines of systemic treatment, and 43% had prior checkpoint inhibitor treatment). Treatment related adverse events occurred in 66% of pts, and 15% were grade 3/4. One DLT of grade 4 immune mediated hepatitis was observed at the 900mg dose. EMB-02 showed dose proportional PK across 6-900mg doses, and PK/PD modeling and simulation indicated at least 90% of pts at ≥180mg doses had complete peripheral PD-1 receptor occupancy. Among 47 efficacy evaluable pts, 2 CRs, 1 PR, and 18 SDs were observed per RECIST 1.1. All 3 responders were still under follow up with no PD observed as of the data cut-off date. CBR-24 (CR+PR+ durable SD [≥24wks]) was 19% (9/47).

Conclusions

EMB-02 has demonstrated a tolerable safety profile and encouraging anti-tumor activity during the dose escalation phase, warranting further development. Expansion cohorts in select advanced solid tumours are ongoing.

Clinical trial identification

NCT04618393.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai EpimAb Biotherapeutics Co., Ltd.

Funding

Shanghai EpimAb Biotherapeutics Co., Ltd.

Disclosure

S. Zeng, Q. Lu, C. Jiang, F. Ren, X. Wu: Financial Interests, Personal, Full or part-time Employment: Shanghai EpimAb Biotherapeutics Co., Ltd. All other authors have declared no conflicts of interest.