Phase 1 dose-escalation study of SEA-CD40: a non-fucosylated CD40 agonist, in advanced solid tumors and lymphomas.

Background: SEA-CD40 is an investigational, non-fucosylated, humanized monoclonal IgG antibody that activates CD40, an immune-activating tumor necrosis factor receptor superfamily member. SEA-CD40 exhibits enhanced binding to activating FcγRIIIa, possibly enabling greater immune stimulation than other CD40 agonists. A first-in-human phase 1 trial was conducted to examine safety, pharmacokinetics, and pharmacodynamics of SEA-CD40 monotherapy in patients with advanced solid tumors and lymphoma.

A League of Its Own? Established and Emerging Therapies in Undifferentiated Pleomorphic Sarcoma.

Over the last decade in soft tissue sarcoma (STS) research, the shifting landscape towards more precise subtype classification and the increasing study of novel therapeutic strategies has prompted a need to highlight current knowledge of effective subtype specific therapies. Undifferentiated pleomorphic sarcoma (UPS), formerly known as malignant fibrous histiocytoma (MFH), is among the most common subtypes of STS arising in the trunk or extremities of adults. Administration of systemic chemotherapy is the primary management in locally advanced and metastatic UPS.

Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers.

Background: Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers.

Patients And Methods: Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431).

Sinonasal Squamous Cell Carcinoma Survival Outcomes Following Induction Chemotherapy vs Standard of Care Therapy.

Objective: To compare oncologic outcomes in sinonasal squamous cell carcinoma (SNSCC) treated with standard of care (SOC) definitive therapy, consisting of surgery or chemoradiotherapy, vs induction therapy followed by definitive therapy.

Study Design: Retrospective review.

Setting: Academic tertiary care hospital.

Phase II Study of Taselisib in -Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I.

Purpose: mutations frequently contribute to oncogenesis in solid tumors. Taselisib, a potent and selective inhibitor of phosphoinositide 3-kinase, has demonstrated clinical activity in -mutant breast cancer. Whether mutations predict sensitivity to taselisib in other cancer types is unknown.

Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors.

Background: Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors.

Methods: Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified.

Association of Tumor Mutational Burden and Immune Gene Expression with Response to PD-1 Blockade by Sasanlimab Across Tumor Types and Routes of Administration.

Background: Sasanlimab is a monoclonal antibody that binds to the programmed cell death receptor 1 (PD-1). Anti-PD-1 monoclonal antibodies have improved patient clinical outcomes; however, not all treated patients derive clinical benefit. Further insights on potential biomarkers beyond PD-L1 expression levels would help to identify the patients most likely to respond to treatment.

Phase 1 trial of adavosertib (AZD1775) in combination with concurrent radiation and cisplatin for intermediate-risk and high-risk head and neck squamous cell carcinoma.

Background: Adavosertib (AZD1775) is an inhibitor of the Wee1 kinase. The authors conducted a phase 1b trial to evaluate the safety of adavosertib in combination with definitive chemoradiotherapy for patients with newly diagnosed, intermediate-risk/high-risk, locally advanced head and neck squamous cell carcinoma (HNSCC).

Methods: Twelve patients with intermediate-risk/high-risk HNSCC were enrolled, including those with p16-negative tumors of the oropharynx, p16-positive tumors of the oropharynx with ≥10 tobacco pack-years, and tumors of the larynx/hypopharynx regardless of p16 status.

Health Insurance Payer Type and Ethnicity Are Associated with Cancer Clinical Trial Enrollment Among Adolescents and Young Adults.

Adolescents and young adults (AYAs) have experienced inferior improvements in cancer survival outcomes. One potential explanation is the low rate of enrollment in cancer clinical trials. While the reasons behind this are multifactual, sociodemographic factors are probably contributory.

The addition of chemotherapy to adjuvant radiation is associated with inferior survival outcomes in intermediate-risk HPV-negative HNSCC.

Background: Only high-risk tumors with extranodal extension (ENE) and/or positive surgical margins (PSM) benefit from adjuvant therapy (AT) with concurrent chemoradiation (CRT) compared to radiation therapy (RT) in locally advanced head and neck squamous cell carcinoma (HNSCC). Optimal treatment for intermediate-risk tumors remains controversial. We categorized patients based on their surgical pathologic risk factors and described AT treatment patterns and associated survival outcomes.

Immune Checkpoint Markers in Superficial Angiosarcomas: PD-L1, PD-1, CD8, LAG-3, and Tumor-Infiltrating Lymphocytes.

Cutaneous angiosarcomas may express programmed death ligand-1 (PD-L1) and PD-L1 expression, and the presence of tumor-infiltrating lymphocytes (TILs) correlates with outcome. These observations provide a basis for PD-1/PD-L1 inhibitor therapy. Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that interacts with the PD-L1 axis and is considered to be a marker of immune exhaustion.

A multicenter, single-arm, basket design, phase II study of NC-6004 plus gemcitabine in patients with advanced unresectable lung, biliary tract, or bladder cancer.

NC-6004 is a nanoparticle developed using micellar technology that can improve release of cisplatin, a standard treatment for many cancer types, and achieve selective distribution to tumors. Here, in the Phase II portion of this study, the activity, safety, tolerability, and effects on quality of life of NC-6004 in combination with gemcitabine was examined in 34 squamous non-small cell lung carcinoma (NSCLC) patients, 50 biliary tract cancer patients, and 13 bladder cancer patients. All patients received 135 mg/m NC-6004 on day one and 1,250 mg/m gemcitabine on days one and eight.

Novel induction therapy transoral surgery treatment paradigm with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck - Mature clinical and functional outcomes.

Objective: Induction chemotherapy in head and neck squamous cell carcinoma (HNSCCA) has principally been studied prior to radiation therapy. We evaluated pre-operative induction therapy followed by surgery followed by risk-adapted adjuvant therapy. This report details the mature 5-year survival statistics, clinical and functional outcomes.

A Phase 1b Dose Escalation Trial of NC-6300 (Nanoparticle Epirubicin) in Patients with Advanced Solid Tumors or Advanced, Metastatic, or Unresectable Soft-tissue Sarcoma.

Purpose: NC-6300 is a novel nanoparticle formulation of epirubicin that has a pH-sensitive linker conjugated to epirubicin. It exhibits selective tumor accumulation owing to enhanced permeability and retention effect. We conducted a phase 1b trial to determine MTD and recommended phase II dose (RP2D) of NC-6300 monotherapy in advanced, metastatic, or unresectable solid tumors, including soft-tissue sarcomas.

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication.

Purpose: Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti-PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.

Tissue/Site-Agnostic Study of Ribociclib for Tumors With Cyclin D-CDK4/6 Pathway Genomic Alterations: A Phase II, Open-Label, Single-Arm Basket Study.

Purpose: As part of the Novartis Signature Program, this study evaluated the efficacy of ribociclib (selective cyclin-dependent kinase 4/6 [CDK4/6] inhibitor) in patients with cyclin D-CDK4/6 pathway-aberrant tumors.

Methods: This was a phase II, single-arm, signal-seeking study in patients with advanced malignancies that had progressed on or after standard treatment. Prior identification of tumor mutation or amplification, /3 amplification, or mutation or loss was required.

Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: a multicentre, multigroup, phase 2 trial.

Background: Most head and neck squamous-cell carcinomas (HNSCCs) are driven by p16 inactivation and cyclin D1 overexpression that results in hyperactivation of cyclin-dependent kinase 4 and 6 (CDK4/6), rather than by the human papillomavirus (HPV). Deregulated cyclin D1 expression also causes resistance to EGFR inhibitors. We previously reported that palbociclib (a selective CDK4/6 inhibitor) given with cetuximab (an EGFR inhibitor) was safe.

Assessment of Subcutaneous vs Intravenous Administration of Anti-PD-1 Antibody PF-06801591 in Patients With Advanced Solid Tumors: A Phase 1 Dose-Escalation Trial.

Importance: We assessed feasibility of monthly subcutaneous administration of PF-06801591, a humanized immunoglobulin G4 monoclonal antibody that binds to the programmed cell death (PD-1) receptor and blocks its interaction with PD-1 ligands.

Objective: To evaluate the safety, efficacy, and pharmacokinetics of PF-06801591 administered intravenously vs subcutaneously.

Design, Setting, And Participants: Ongoing phase 1, open-label, multicenter, dose-escalation study of 40 patients, 18 years or older, with locally advanced or metastatic solid tumors, enrolled between March 8, 2016, and March 5, 2018, from 4 US medical centers.

Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer.

Purpose: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

Experimental Design: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16-positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits.

Quality of Life for Patients With Favorable-Risk HPV-Associated Oropharyngeal Cancer After De-intensified Chemoradiotherapy.

Purpose: Oropharynx cancers associated with human papillomavirus (HPV) have a favorable prognosis, but current treatment approaches carry significant long-term morbidity. Strategies to de-intensify treatment in this population are under investigation, but the impact of these approaches on quality of life (QOL) is not well understood. We present patient-reported outcomes from 2 prospective studies examining de-intensified chemoradiotherapy.

Multidisciplinary Management of Oligometastatic Soft Tissue Sarcoma.

Soft tissue sarcomas (STS) encompass a group of rare but heterogeneous diseases. Nevertheless, many patients, particularly those with oligometastatic disease can benefit from thoughtful multimodality evaluation and treatment regardless of the STS subtype. Here, we review surgical, interventional radiology, radiation, and chemotherapy approaches to maximize disease palliation and improve survival, including occasionally long-term disease-free survival.

Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach.

Neoplastic cellularity contributes to the analytic sensitivity of most present technologies for mutation detection, such that they underperform when stroma and inflammatory cells dilute a cancer specimen's variant fraction. Thus, tumor purity assessment by light microscopy is used to determine sample adequacy before sequencing and to interpret the significance of negative results and mutant allele fraction afterwards. However, pathologist estimates of tumor purity are imprecise and have limited reproducibility.

Identification of Clonal Hematopoiesis Mutations in Solid Tumor Patients Undergoing Unpaired Next-Generation Sequencing Assays.

Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing (NGS) assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired Foundation Medicine NGS assays.

Experimental Design: This was a retrospective cohort study of individuals undergoing NGS of solid tumors from two large cancer centers.