The Sentinel


Wednesday, November 11, 2020

SITC 2020 Scientific Highlights – Nov. 11, 2020

The Society for Immunotherapy of Cancer (SITC) is pleased to present scientific highlights from the Nov. 11, 2020, sessions of the 35th Anniversary Annual Meeting.

AXL and PD-1 inhibition may benefit select patients with non-small cell lung cancer

A PhII study of bemcentinib, a first-in-class selective AXL kinase inhibitor, in combination with pembrolizumab in pts with previously-treated advanced NSCLC: Updated clinical & translational analysis

James Spicer, PhD FRCP (King’s College London), discussed the BGBC008 trial, investigating the combination of the AXL inhibitor bemcentinib with pembrolizumab for non-small cell lung cancer. Results were presented for the cohort of patients who had progressed on prior immunotherapy with the primary endpoint of overall response rate.

Sixteen patients were included in this analysis, all of whom had been treated with an immune checkpoint inhibitor as their most recent therapy. Biomarker status was available for 13 patients: 8 were cAXL-positive while 5 were negative, and 5 patients had PD-L1 TPS >=50%, 5 had TPS of 1-49%, and 3 had TPS <1%. Responses to the combination therapy were only observed in patients with cAXL positivity (combined tumor and immune cell expression), as 1 partial response and 5 stable disease results were recorded in these seven patients. Median PFS for AXL-positive patients was 4.73 months compared to 1.87 months for cAXL-negative. Common treatment-emergent adverse events included liver enzyme elevations and diarrhea. The authors proposed that AXL may promote T cell dysfunction and exhaustion, among other mechanisms, and blocking this function could potentiate immune checkpoint blockade therapy, even in these patients who progressed on prior immunotherapy.

Combination of bempegaldesleukin and nivolumab results in long PFS in melanoma

Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study

Updated results from the PIVOT-02 study, investigating the combination of nivolumab and the IL-2 pathway agonist bempegaldesleukin, were presented by Adi Diab, MD (MD Anderson Cancer Center). Patients (n=41) were eligible for the trial if they had previously untreated metastatic melanoma and were evaluated for the primary endpoints of overall response rate and safety.

The median follow-up for this report was 29.0 months. At this time, the ORR was 53%, including a complete response rate of 34%. The median time to response was 2.0 months, and to complete response was 7.9 months. The median PFS was 30.9 months, and the median overall survival was not reached. The 36-month OS rate was 70.9%. Biomarker studies revealed signatures that correlated with response, including the interferon-gamma gene expression profile and CD8+ TILs in baseline samples. Dynamic changes in the peripheral blood were also observed after the first dose of treatment, resulting in increases in the polyfunctional strength index of CD4+ and CD8+ T cells, and in the level of circulating eosinophils. The encouraging findings in this phase 2 trial have led to the initiation of a phase 3 trial of the same combination.

Neoadjuvant oncolytic virus therapy may benefit patients with melanoma

3-year results of the phase 2 randomized trial for talimogene laherparepvec (T-VEC) neoadjuvant treatment plus surgery vs surgery in patients with resectable stage IIIB-IVM1a melanoma

Reinhard Drummer, MD (University Hospital of Zurich), and colleagues studied the use of talimogene laherparepvec (T-VEC) as a neoadjuvant treatment for patients with resectable melanoma in a phase 2 trial. This presentation provided an interim analysis of the impact of neoadjuvant T-VEC compared to surgery alone with a median follow up of 41.3 months.

The primary analysis of recurrence-free survival indicated improved outcomes with neoadjuvant T-VEC, as these patients experienced 3-year RFS rates of 46.5% compared to 31.0% with surgery alone by Kaplan-Meier estimates. Removing potential effects of subsequent therapies increased the difference between the two arms, with estimated 3-year RFS of 49.1% with T-VEC and 22.9% without. Overall survival was also greatly improved with neoadjuvant therapy: 3-year estimates were 83.2% compared to 71.6%. This first trial of neoadjuvant oncolytic virus therapy is therefore showing encouraging results and warrants continued evaluation.

Study compares neoadjuvant options for non-small cell lung cancer

Combined neoadjuvant chemo-immunotherapy therapy achieves superior downstaging of resectable non-small cell lung cancer as compared to chemotherapy, mono or dual immunotherapy

As neoadjuvant approaches with immunotherapies are gaining attention, Boris Sepesi, MD (MD Anderson Cancer Center), and colleagues compared outcomes with four treatment options: platinum doublet chemotherapy, nivolumab, nivolumab + ipilimumab, or nivolumab + doublet chemotherapy. The patient cohorts were pulled from institutional records and the NEOSTAR study, and were diagnosed with stage I-IIIA NSCLC.

The highest rate of overall clinical-to-pathological downstaging (ypT and/or ypN) was found in the cohort of patients treated with nivolumab and chemotherapy at 68%, while all three other treatment options led to overall downstaging rates of 38% (p=0.048). Upstaging rates also favored patients receiving nivolumab and chemotherapy, as only 14% of these patients were upstaged at the time of surgery, compared to 28% of the chemotherapy cohort and 38% of patients in both the nivolumab and nivolumab + ipilimumab cohorts. The only evaluation that did not favor the nivolumab + chemotherapy treatment was the ypN downstaging, where the lowest rate of downstaging (42%) was seen with this treatment and the highest rate (55%) with chemotherapy. While these downstaging rates are encouraging, it remains to be seen whether these rates in small cohorts extend to improved survival.

Combination nivolumab and intratumoral therapy may be promising neoadjuvant option for melanoma

Phase II Trial of Neoadjuvant Nivolumab (Nivo) and Intra-Tumoral (IT) CMP-001 in High-Risk Resectable Melanoma (Neo-C-Nivo): Final Results

Diwakar Davar, MD (UPMC Hillman Cancer Center), discussed a trial of combination nivolumab and intratumoral CMP-001 (a CpG packaged in a virus-like particle) in patients with high-risk resectable melanoma. Thirty patients were treated with a combination of neoadjuvant and adjuvant therapy. The neoadjuvant portion included seven weeks of weekly CMP-001 delivered intratumorally after the first week and three doses of nivolumab. After resection, nivolumab and CMP-001 were dosed every four weeks for 48 weeks. Primary goals of the study were to evaluate major pathological response rate and safety.

All but one patient completed the full neoadjuvant therapy cycle, with two patients discontinuing CMP-001 due to toxicity. Radiographic analysis indicated response in 43% of patients and stable disease in 30%. Pathologic responses included complete response in 50%, major pathologic response in 10%, and partial response in 10%. Biomarker analysis indicated that responding tumors had increased levels of CD8+ TIL and CD303+ plasmacytoid dendritic cells. The median relapse-free survival has not been reached in patients with pathological responses, leading the investigators to continue further investigation of this combination.

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