(P 112) PHASE 1/2 STUDY OF YH001, A CTLA-4 ANTIBODY WITH THE SUBCUTANEOUSLY ADMINISTERED PD-L1 ANTIBODY ENVAFOLIMAB, WITH OR WITHOUT DOXORUBICIN IN PATIENTS WITH ADVANCED OR METASTATIC SOFT TISSUE SARCOMA

Objective: Doxorubicin is the standard frontline chemotherapeutic used in sarcoma patients and has been well tolerated when combined with PD-(L)1 antibodies. Given the non-overlapping toxicity profiles of checkpoint inhibitors and chemotherapy, the addition of dual checkpoint inhibition using the CTLA-4 antibody YH001 and PD-L1 antibody envafolimab combined with or without doxorubicin may improve response rates in patients with advanced or metastatic sarcoma, without undue toxicity.

Methods: This is a multicenter, open label, Phase 1/2 study. The Phase 1 portion includes the combination of YH001 (either 2 mg/kg or 4 mg/kg i.v. Q3W) and envafolimab ( 600 mg SQ Q3W) dual immunotherapy in sarcoma patients refractory to or intolerant to standard treatment (i.e., doublet therapy at two YH001 dose levels of > 6 patients each) and YH001 and envafolimab in combination with of doxorubicin (75 mg/m2 Q3W up to six doses) in patients who have not received prior doxorubicin treatment (i.e., triple therapy at two YH001 dose levels of > 6 patients each). Phase 2 cohorts will assess the efficacy of triple therapy in patients with advanced or metastatic LMS or DDLS who are candidates for doxorubicin and have not received doxorubicin or immune checkpoint inhibitor treatment and doublet therapy in patients with advanced or metastatic ASPS and chondrosarcoma who have not received immune checkpoint inhibitor treatment.

Results: As of June 1, 14 patients were enrolled (male:female 8:6, median age = 62 years; all ECOG = 1; 12 White, 1 Asian, 1 other) in the phase 1 portion. Six patients each received YH001 at 2 mg/kg or 4 mg/kg with envafolimab (doublet therapy) resulting in one DLT of grade 3 thyroiditis at the higher YH001 dose. Two patients received triple therapy with YH001 at 2 mg/kg and one patient experienced a DLT of grade 3 fatigue that required doxorubicin dose reduction. The most frequent YH001 related AE was grade 1 or grade 2 pruritis (N=3). Ongoing partial responses have been observed in a patient with angiosarcoma on doublet therapy and in a patient with dedifferentiated chondrosarcoma on triple therapy.

Conclusion: YH001 has been tolerable with envafolimab with or without doxorubicin and evidence of activity has been observed for doublet and triplet therapy.