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Aims: Sitravatinib, a spectrum-selective tyrosine kinase inhibitor targeting TAM receptors (Tyro3/Axl/MerTK) and VEGFR2, demonstrated antitumour and immune-modulatory activity. Tislelizumab, ananti-PD-1 antibody engineered to minimize binding to FcgammaR on macrophages and abrogate antibody-dependent phagocytosis, showed clinical activity in advanced solid tumours. We report results from the PROC cohort of an ongoing multicohort phase 1b study (BGB-900-103; NCT03666143) assessing safety/tolerability and preliminary antitumour activity of sitravatinib+tislelizumab. Methods :Anti-PD-(L)antibody-naive patients with histologically confirmed advanced PROC (disease progression < 6 months after last platinum treatment), but not platinum-refractory disease, were eligible. Patients received oral sitravatinib 120 mg QD plus intravenous tislelizumab 200 mg Q3W. The primary endpoint was safety/tolerability; key secondary and exploratory endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). PD-L11 (Ventana SP263) and plasma VEGF/serum CXCL10 assessments were retrospective. Results : As of October 13, 2020, 60 PROC patients (median age, 64 years; median of four prior regimens) were enrolled; 13 (22%) remained on treatment. Median follow-up was 6.0 months. Treatment-emergent adverse events (TEAEs) of any grade/grade >=3 occurred in 97%/68% of patients; TEAEs led to sitravatinib dose reduction in 50% of patients. Hypertension (18%) and abdominal pain (12%) were the most common grade >=3 TEAEs. Four fatal AEs were deemed unrelated to treatment. Among 53 evaluable patients, ORR was 26% (95% CI, 15.3-400.3; partial response, n = 14); DCR was 77% (95% CI, 63.8-87.7). Median duration of response was 4.7 months (95% CI, 2.83-NE). There was no clear association between PD-L1 expression and clinical response; plasma VEGF and serum CXCL10 increased after treatment (P < 0.0001 for both). Median PFS was 4.1 mo

Background: Patients (pts) with advanced NSCLC often develop progressive disease, with limited treatments for pts who are heavily pretreated with anti-PD-(L)1 antibodies and/or chemotherapy. Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM and VEGFR2 receptors, which can reduce the number of myeloid-derived suppressor cells, regulatory T cells, and increases the ratio of M1/M2 polarized macrophages, potentially augmenting antitumor responses. Tislelizumab, is an anti-PD-1 antibody engineered to minimize binding to FcgR on macrophages to abrogate antibody-dependent phagocytosis, a potential mechanism of resistance. This phase Ib study assessed safety/tolerability and antitumor activity of sitravatinib + tislelizumab in solid tumors (NCT03666143). We report results from NSCLC cohorts. Method(s): Pts had confirmed metastatic nonsquamous (NSQ) or squamous (SQ) NSCLC treated with 1-3 lines of prior systemic therapy with/without an anti-PD-(L)1 inhibitor. Pts with EGFR/ BRAF mutations or ALK/ROS1 rearrangements were ineligible. Sitravatinib was given 120 mg orally QD and tislelizumab 200 mg IV Q3W. The primary endpoint was safety/tolerability. Secondary endpoints were objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and progression-free survival (PFS). Result(s): On 13 Oct 2020, 75 pts (NSQ, n=46; SQ, n=29) were treated; 47 pts were refractory/resistant (R/R) to PD-(L)1 therapy and 28 pts were PD-(L)1 naive. Median age was 60 yrs (range: 25-79). Median study follow-up was 10.1 mo (range: 0.4-18.8). All pts had a treatment-emergent adverse event (TEAE); 73% of pts had a Grade >=3 TEAE (most common: hypertension [n=12]). Confirmed ORR was 17% (95% CI: 9.1-27.7); DCR was 85% (95% CI: 74.0-92.0). Median DoR was 7.0 mo (95% CI: 2.9-not estimable). Median PFS was 5.5 mo (95% CI: 4.1-7.0). There was a trend toward higher ORR in pts with PD-L1 IC expression >=10%. In R/R pts confirmed ORR was 14% (95% CI: 5.2-27.4)

Background: Patients with metastatic non-small cell lung cancer (NSCLC) who are refractory/resistant (R/R) to anti-PD-(L)1 therapies have limited treatment options. Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM and VEGFR2 receptors, which can reduce the number of myeloid-derived suppressor cells, regulatory T cells, and increase the ratio of M1/M2 polarized macrophages, potentially augmenting antitumor immune responses. Tislelizumab, is an anti-PD-1 antibody engineered to minimize binding to FcgR on macrophages to abrogate antibody-dependent phagocytosis, a potential mechanism of resistance. This phase Ib study assessed safety/tolerability and antitumor activity of sitravatinib + tislelizumab in solid tumors (NCT03666143). We report results from NSCLC cohorts. Method(s): Eligible patients had metastatic non-squamous (NSQ) or squamous (SQ) NSCLC with radiographic disease progression on/after anti-PD-(L)1 therapy as their most recent treatment. Patients with EGFR/BRAF mutations or ALK/ROS1 rearrangements were ineligible. Treatment included sitravatinib 120 mg orally QD and tislelizumab 200 mg IV Q3W. The primary endpoint was safety and tolerability. Key secondary endpoints included investigator-assessed objective response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS). Result(s): As of 13 Oct 2020, 47 patients with NSQ (n=24) and SQ (n=23) NSCLC were enrolled with a median study follow-up of 7.8 months (range: 0.4-18.1). Median age was 60 years (range: 25-79) and 72% of patients had >=2 lines of prior therapies. All patients had a treatment-emergent adverse event (TEAE); 68% had a grade >=3 TEAE (most common: hypertension, 19%). Confirmed ORR was 14% (95% CI: 5.2-27.4) and DCR was 86% (95% CI: 72.7-94.8). Median DoR was 6.9 months (95% CI: 3.1-NE). Median PFS was 5.2 months (95% CI: 4.1-5.9). There was no association between PD-L1 expression and clinical response. Conclusion(s): Sit

Background: Combining a PD-1 inhibitor and an agent with immune modulatory and antitumor properties may enhance antitumor activity of either agent. Sitravatinib, a spectrum-selective TKI targeting TAM receptors (Tyro3/Axl/MerTK) and VEGFR2, reduces the number of myeloid-derived suppressor cells and regulatory T cells while increasing the ratio of M1/M2-polarized macrophages, which may overcome an immunosuppressive tumor microenvironment and augment antitumor immune responses. Tislelizumab, an anti-PD-1 antibody engineered to minimize binding to FcgammaR on macrophages and abrogate antibody-dependent phagocytosis, has shown single-agent clinical activity in patients (pts) with advanced solid tumors. This open-label, multicohort, phase 1b study assessed safety/tolerability and preliminary antitumor activity of sitravatinib + tislelizumab in advanced solid tumors (BGB-900-103; NCT03666143). We report results from the PROC cohort. Method(s): Anti-PD-(L)1 antibody-naive pts with histologically confirmed, advanced PROC (disease progression <6 mo after last platinum treatment) were enrolled. While platinum-resistant pts were included, pts with platinum-refractory disease were excluded. Patients received sitravatinib 120 mg PO QD and tislelizumab 200 mg IV Q3W. Primary endpoint was safety/tolerability of sitravatinib + tislelizumab. Key secondary endpoints were investigator-assessed objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) per RECIST v1.1; overall survival (OS) was also assessed. PD-L1 IHC assay (Ventana SP263) and assessment of plasma VEGF/serum CXCL10 were retrospective. Result(s): As of Oct 13, 2020, 60 PROC pts were enrolled; 13 (22%) remained on treatment. Median age was 64 yrs (range 26-80); pts received a median of 4 (range 1-11) prior regimens. Median follow-up was 6.0 mo (range 0.2-23.4). Treatment-emergent adverse events (TEAEs) of any grade/grade >=3 occurred in 97%/68% of pts; TEAEs led to sitravatinib dose r

© The Institution of Engineering and Technology 2017. Previous research on the characteristic basis function method (CBFM) has shown that the use of the ultra-wide band CBFM can efficiently solve the problem of computing the broadband monostatic radar cross-section (RCS) of a target by reducing the size of the associated impedance matrix and avoiding the repeated generation of the macro base functions. However, it is still necessary to repeatedly construct the reduced matrix at each frequency in the analysed frequency band, and an interpolation method is proposed to address this problem. It is shown that it is only needed to generate and store the reduced matrices at four frequency samples to cover the entire frequency band, and efficiently derive the reduced matrices at other frequencies via simple interpolation. Numerical results are given to demonstrate the accuracy and efficiency of the proposed method.