1110P - A phase II clinical trial of SHR-1701 combined with temozolomide for advanced melanoma

Background

Immune checkpoint inhibitors (ICIs) have limited efficacy in advanced melanoma in Asians, and chemotherapy is still an important option. Temozolomide (TMZ) has been recommended in guidelines for treatment of melanoma. SHR-1701 is a bifunctional fusion protein composed of a mAb against PD-L1 fused to the extracellular domain of TGF-β receptor II. Here, we report the safety and efficacy of SHR-1701 combined with TMZ in advanced melanoma.

Methods

In this single-center, phase II study, patients(pts) with advanced melanoma were eligible. Prior ICIs plus TMZ and progressed within 6 months was not permitted. Pts received SHR-1701(30 mg/kg IV Q3W) combined with TMZ (150 mg/m² IV, Days 1-5 Q3W) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST1.1. Secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. A standard Simon two-stage design was used. If there were more than 5 responses in 21 pts in stage I, the study would continue to 31 pts in stage II.

Results

As of March 31, 2023, 21 pts were enrolled. Various histology subtypes were included (16 acral, 2 mucosal, 2 cutaneous, 1 unknown histology subtype). The median age was 54 years (range, 34-73), most patients were male (52.4%), 18 pts (85.7%) were ECOG PS 1, 15 pts (71.4%) were stage IV. Received previous 0/1/2 lines of systemic treatment were 14(66.7%)/4(19.0%)/3(14.3%) pts. The median follow-up was 4.4 months（range, 0.5 to 12.7 months). At the data cutoff, 12 pts remained on treatment. Of 16 evaluable pts, 7 pts had partial response, and 6 pts had stable disease. The unconfirmed ORR and DCR were 43.8% and 81.3%, respectively. After treatment, 3 pts with solitarily metastatic lesions received curative surgery. Of 21 pts, the incidence of treatment-related adverse events (TRAEs) was 47.6%, most commonly anemia, γ-glutamyltransferase increase and rash (14.3% each). The incidence of grade 3 TRAEs was 14.3%. No grade ≥ 4 TRAEs occurred.

Conclusions

SHR-1701 plus TMZ showed promising antitumor activity in advanced melanoma pts, and was generally well tolerated.

Clinical trial identification

NCT05106023; released in November 3, 2021.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.