A retrospective study to evaluate the safety and efficacy of anlotinib plus camrelizumab in management of advanced retroperitoneal sarcoma.

e23545 Background: Several studies have demonstrated the antitumor activity of single-agent anlotinib in the treatment of soft tissue sarcoma (STS). However, the most effective results were from cases of alveolar soft part sarcoma (ASPS), which was a rare subtype in retroperitoneal sarcoma (RPS). The therapy of RPS is still dismal. Thus, we evaluated the effectiveness and safety of anlotinib plus camrelizumab for the treatment of RPS. Methods: We retrospectively reviewed the data of 36 patients with advanced/metastatic RPS in Sarcoma Centre of Peking University Cancer Hospital from July 2019 to February 2021. Anlotinib was given 12mg Qd 2 weeks on and 1 week off, and camrelizumab was transfused 200mg at Q3w. Patients that underwent at least 4 cycles of therapy were enrolled in this study. The primary endpoint is objective response rate (ORR) and evaluated according to the irRECIST 1.1 criteria. Results: The pathologic subtypes of enrolled cases include liposarcoma (LP) (n = 16), leiomyosarcoma (LMP) (n = 5), uncertain differentiation sarcoma (n = 7), fibroblastic and myofibroblastic tumours (n = 4), rhabdomyosarcoma (n = 2) and malignant peripheral nerve sheath tumour (MPNST) (n = 2). Two patients (5.6%) achieved CR and 9 patients (25.0%) achieved PR, with an ORR of 30.6%. Eighteen patients (50.0%) achieved SD and 7 patients (19.4%) were evaluated as PD, with the disease control rate (DCR) of 80.6%. The progression-free rate (PFR) at six months was 60.0%. Five patients underwent further radical surgical resection. The two CR cases were diagnosed as dedifferentiated liposarcoma (DDLP) and MDM2 amplified MPNST respectively, and both patients have been under CR status for over 12 months until now. The only grade 3 or higher treatment related adverse event was hypertension (22.2%). Camrelizumab related reactive cutaneous capillary endothelial proliferation (RCCEP) was not observed in this group of patients. Conclusions: The combination of anlotinib and camrelizumab demonstrated encouraging efficacy and safety in the treatment of RPS. A further clinical study with biomarker exploration should be performed in the future.

Keynote-200 phase 1b: A novel combination study of intravenously delivered coxsackievirus A21 and pembrolizumab in advanced cancer patients.

TPS3108 Background: Coxsackievirus A21 (CVA21, CAVATAK) is a naturally occurring ICAM-1 targeted oncolytic immunotherapeutic virus. Pembrolizumab is a human programmed death receptor-1 (PD-1) blocking antibody that has yielded significant solid tumor responses via reversal of tumor induced T-cell suppression. Intravenous (i.v.) CVA21 mono-therapy is generally well tolerated, with low toxicity and can successfully target tumors in patients with melanoma, NSCLC and bladder cancer as confirmed by detection of CVA21 viral RNA in post-treatment tumor biopsies (Pandha et al., 2016). Intratumoral CVA21 replication has the potential to up-regulate numerous key immune checkpoint molecules, including PD-L1 (Andtbacka et al., 2016).The combination of i.v. CVA21+pembrolizumab may translate to a potential enhanced benefit in the clinic. Methods: The Phase Ib KEYNOTE-200 (NCT02043665) Treatment: Primary objectives are to assess dose-limiting toxicities (DLT) of CVA21 in combination with pembrolizumab. Secondary objectives are to assess ORR by irRECIST 1.1 criteria, PFS, and OS. Patients (pts) are infused with CVA21 in 100 mL saline + pembrolizumab. In Cohort 1 (n = 3), CVA21 is administered at a dose of 1 x 108 TCID50, in Cohort 2 (n = 3) at a dose of 3 x 108 TCID50 and in Cohort 3 (n = ~80) at a dose of 1 x 109 TCID50 on study days 1,3,5,8,29,and Q3W for 6 additional infusions. Pembrolizumab is given in all cohorts at 200 mg IV Q3W from Day 8 for up to 2 years. Treatment (tx) with CVA21 + pembrolizumab will continue until confirmed CR or PD (whichever comes first) per irRECIST 1.1 or DLT.To date the combination of intravenous CVA21 and pembrolizumab has been generally well-tolerated. At present one gr 3 CVA21-related hyponatremia with no DLT for the combination of CVA21 and pembrolizumab being observed. Enrolment in Cohorts 1 and 2 is complete with tx of pts in Cohort 3 currently underway. Key eligibility: Pts with advanced disease considered appropriate tx with CVA21 + pembrolizumab, lesion(s) accessible for core biopsy, ECOG PS 0-1, no active cerebral metastases, no autoimmunity/immunosuppression. Clinical trial information: NCT02043665.