Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols.

Immunotherapy of cancer is now an essential pillar of treatment for patients with many individual tumor types. Novel immune targets and technical advances are driving a rapid exploration of new treatment strategies incorporating immune agents in cancer clinical practice. Immunotherapies perturb a complex system of interactions among genomically unstable tumor cells, diverse cells within the tumor microenvironment including the systemic adaptive and innate immune cells.

ACR Appropriateness Criteria® Staging and Post-Therapy Assessment of Head and Neck Cancer.

Imaging of head and neck cancer at initial staging and as part of post-treatment surveillance is a key component of patient care as it guides treatment strategy and aids determination of prognosis. Head and neck cancer includes a heterogenous group of malignancies encompassing several anatomic sites and histologies, with squamous cell carcinoma the most common. Together this comprises the seventh most common cancer worldwide.

Biomarkers predictive of response to pembrolizumab in head and neck cancer.

Background: We performed an integrated biomarker evaluation in pembrolizumab-treated patients with R/M HNSCC enrolled in KEYNOTE-012 or KEYNOTE-055. The relationship between biomarkers and HPV status was explored.

Methods: We evaluated PD-L1 (combined positive score [CPS]), TMB, T-cell-inflamed gene expression profile (Tcell GEP), and HPV status.

Liquid Biopsy Assessment of Circulating Tumor Cell PD-L1 and IRF-1 Expression in Patients with Advanced Solid Tumors Receiving Immune Checkpoint Inhibitor.

Background: Reliable biomarkers that can be serially monitored to predict treatment response to immune checkpoint inhibitors (ICIs) are still an unmet need. Here, we present a multiplex immunofluorescence (IF) assay that simultaneously detects circulating tumor cells (CTCs) and assesses CTC expression of programmed death ligand-1 (PD-L1) and interferon regulatory factor 1 (IRF-1) as a candidate biomarker related to ICI use.

Objective: To assess the potential of CTC PD-L1 and IRF-1 expression as candidate biomarkers for patients with advanced epithelial solid tumors receiving ICIs.

Dry powders for inhalation containing monoclonal antibodies made by thin-film freeze-drying.

Thin-film freeze-drying (TFFD) is a rapid freezing and then drying technique used to prepare inhalable dry powders from the liquid form for applications such as drug delivery to the lungs. Herein we report the preparation of aerosolizable dry powders of monoclonal antibodies (mAbs) by TFFD. We first formulated an IgG antibody with lactose/leucine (60:40, w/w) or trehalose/leucine (75:25) and tested their aerosol performance.

Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma.

Background: To characterize genomic determinants of response to pembrolizumab in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 study.

Methods: Associations between biomarkers (tumor mutational burden (TMB), neoantigen load (NL), 18-gene T-cell-inflamed gene expression profile (TcellGEP), and PD-L1 combined positive score (CPS)) and clinical outcomes with pembrolizumab were assessed in patients with R/M HNSCC (n=192). Tumor human papillomavirus (HPV) status was also evaluated with the use of p16 immunohistochemistry and whole exome sequencing (WES; HPV, mapping >20 HPV reads) in pretreatment tumor samples (n=106).

Factors associated with time to EGFR TKI treatment in patients with non-squamous metastatic non-small-cell lung cancer.

Assess factors associated with EGFR TKI initiation among patients with metastatic non-small-cell lung cancer (mNSCLC). Medicare Part D patients diagnosed with non-squamous mNSCLC and starting an EGFR TKI within 1 year of diagnosis were selected from the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Associations between patient characteristics and time from diagnosis to treatment initiation (time-to-treatment [TTT]) were analyzed.

ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non-Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges.

Purpose: Central nervous system metastases are a prominent cause of morbidity and mortality in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). The phase II ASCEND-7 (NCT02336451) study was specifically designed to assess the efficacy and safety of the ALK inhibitor (ALKi) ceritinib in patients with ALK+ NSCLC metastatic to the brain and/or leptomeninges.

Patients And Methods: Patients with active brain metastases were allocated to study arms 1 to 4 based on prior exposure to an ALKi and/or prior brain radiation (arm 1: prior radiotherapy/ALKi-pretreated; arm 2: no radiotherapy/ALKi-pretreated; arm 3: prior radiotherapy/ALKi-naïve; arm 4: no radiotherapy/ALKi-naïve).

Evorpacept alone and in combination with pembrolizumab or trastuzumab in patients with advanced solid tumours (ASPEN-01): a first-in-human, open-label, multicentre, phase 1 dose-escalation and dose-expansion study.

Background: Both innate and adaptive immune responses are important components of anticancer immunity. The CD47-SIRPα interaction could represent an important pathway used by tumour cells to evade immune surveillance. We aimed to evaluate the safety, pharmacokinetics, pharmacodynamics, and anticancer activity of evorpacept (also known as ALX148), a high-affinity CD47-blocking protein with an inactive IgG Fc region in patients with solid tumours.

First-In-Human, First-In-Class, Phase I Trial of the Fucosylation Inhibitor SGN-2FF in Patients with Advanced Solid Tumors.

Lessons Learned: Inhibition of glycoprotein fucosylation, as monotherapy and in combination with immune checkpoint blockade, is a promising therapeutic strategy for treating a broad range of cancers. In this first-in-human, first-in-class, phase I study in advanced solid tumors, SGN-2FF demonstrated dose-proportional pharmacokinetics, evidence of pharmacodynamic target inhibition of glycoprotein fucosylation, and preliminary antitumor activity. SGN-2FF was associated with thromboembolic events that led to study termination.

A Phase II study of nab-Paclitaxel (nab-P) in patients with advanced non-small cell lung cancer with EGFR mutations after frontline tyrosine kinase inhibitor therapy.

Background: Patients with metastatic non-small cell lung cancer (NSCLC) harboring a sensitizing EGFR mutation have effective targeted therapy options initially but most patients eventually progress and receive cytotoxic chemotherapy. In this single-institution phase II study, we evaluated the role of nab-paclitaxel monotherapy in this patient population.

Patients And Methods: Patients with metastatic NSCLC with an activating EGFR mutation whose disease progressed after frontline tyrosine kinase inhibitor therapy and who were chemotherapy naïve received nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 in a 28-day cycle.

A Phase Ib Open-Label, Multicenter Study of Inhaled DV281, a TLR9 Agonist, in Combination with Nivolumab in Patients with Advanced or Metastatic Non-small Cell Lung Cancer.

Purpose: Although PD-(L)1 inhibitors have shown efficacy in advanced/metastatic non-small cell lung cancer (NSCLC), many patients do not respond to this treatment and more effective combinations with acceptable toxicities are needed. To assess the potential benefit of combining localized innate immune stimulation with checkpoint blockade, the TLR9 agonist DV281 was combined with nivolumab in a phase Ib study.

Patients And Methods: Patients after one or two prior lines of systemic therapy were enrolled in a dose-escalation study with a 3+3 design.

A Phase 1 study of gefitinib combined with durvalumab in EGFR TKI-naive patients with EGFR mutation-positive locally advanced/metastatic non-small-cell lung cancer.

Background: EGFR tyrosine kinase inhibitors (TKIs) induce cytolysis and release of tumour proteins, which can stimulate antigen-specific T cells. The safety and efficacy of durvalumab and gefitinib in combination for TKI-naive patients with advanced EGFRm NSCLC was evaluated.

Methods: This Phase 1 open-label, multicentre trial (NCT02088112) was conducted in 56 patients with NSCLC.

Unmet needs and opportunities for improving care for patients with advanced lung cancer on targeted therapies: a qualitative study.

Objective: Lung cancer is increasingly recognised as a heterogeneous disease. Recent advances with targeted therapies for lung cancer with oncogenic mutations have greatly improved the prognosis for this subset of patients, yet little is known about their experiences. This study aimed to identify the needs and explore the healthcare experiences of these advanced patients with oncogenic mutation driven lung cancer.

Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer.

Epacadostat is a potent and highly selective inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1). Here we report results from the open-label, dose-escalation, Phase 1b ECHO-110 study evaluating epacadostat plus atezolizumab in patients with previously treated Stage IIIB/IV nonsmall cell lung cancer (NSCLC). Eligible patients had received ≥1 prior line of platinum-based chemotherapy (≥2 cycles) and no prior checkpoint/IDO inhibitors treatment.

A Phase II Trial of Pembrolizumab and Vorinostat in Recurrent Metastatic Head and Neck Squamous Cell Carcinomas and Salivary Gland Cancer.

Purpose: This clinical trial combined pembrolizumab and vorinostat in recurrent/metastatic squamous cell carcinomas of the head and neck (HN), and salivary gland cancer (SGC).

Patients And Methods: Patients with progressing incurable HN and SGC, Eastern Cooperative Oncology Group (ECOG) ≤1, no prior immunotherapy, RECIST1.1 measurable disease, and normal organ function were eligible.

Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis.

Background: Phase 3 clinical data has shown higher proportions of patients with objective response, longer response duration, and longer overall survival with nivolumab versus docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival.

Methods: We pooled data from four clinical studies of nivolumab in patients with previously treated NSCLC (CheckMate 017, 057, 063, and 003) to evaluate survival outcomes.

Wound Complications in Head and Neck Squamous Cell Carcinomas After Anti-PD-1 Therapy.

Immune checkpoint inhibitors have demonstrated activity in recurrent/metastatic head and neck squamous cell cancer, but less is known regarding their long-term sequelae. We describe four patients who, after complete responses to anti-PD-1 therapy, developed complications requiring surgical intervention. Patient 1 is a 57-year-old female whose marked tumor regression exposed some mandibular hardware.

Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012.

Background: Second-line treatment options for advanced head and neck squamous cell carcinoma (HNSCC) are limited. The phase Ib KEYNOTE-012 study evaluated the safety and the efficacy of pembrolizumab for the treatment of HNSCC after long-term follow-up.

Methods: Multi-centre, non-randomised trial included two HNSCC cohorts (initial and expansion) in which 192 patients were eligible.

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC.

Introduction: This phase I study evaluated nivolumab combined with erlotinib in patients with advanced EGFR-mutant NSCLC.

Methods: Patients with advanced EGFR-mutant NSCLC who were EGFR tyrosine kinase inhibitor (TKI)-naive or TKI-treated but had not received chemotherapy were treated with nivolumab 3 mg/kg every 2 weeks and erlotinib 150 mg/d until disease progression or unacceptable toxicity. The primary objective was safety and tolerability.