Dual checkpoint targeting of B7-H3 and PD-1 with enoblituzumab and pembrolizumab in advanced solid tumors: interim results from a multicenter phase I/II trial.

Background: Availability of checkpoint inhibitors has created a paradigm shift in the management of patients with solid tumors. Despite this, most patients do not respond to immunotherapy, and there is considerable interest in developing combination therapies to improve response rates and outcomes. B7-H3 (CD276) is a member of the B7 family of cell surface molecules and provides an alternative immune checkpoint molecule to therapeutically target alone or in combination with programmed cell death-1 (PD-1)-targeted therapies.

First-in-Human Phase I Study of Merestinib, an Oral Multikinase Inhibitor, in Patients with Advanced Cancer.

Background: The purpose of this nonrandomized, open-label, phase I study (NCT01285037) was to evaluate the safety and tolerability of merestinib, an oral antiproliferative and antiangiogenic kinase inhibitor, and to determine a recommended phase II dose and schedule for patients with advanced cancer.

Materials And Methods: This was a multicenter, nonrandomized, open-label, phase I study of oral merestinib consisting of six parts: dose escalation (part A), followed by a four-cohort dose-confirmation study (part B) and subsequently a four-part dose expansion and combination safety testing of merestinib with standard doses of cetuximab (part C), cisplatin (part D), gemcitabine and cisplatin (part E), and ramucirumab (part F) in patients with specific types of advanced cancers. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated in all cohorts.

Clinical Trial Accrual Targeting Genomic Alterations After Next-Generation Sequencing at a Non-National Cancer Institute-Designated Cancer Program.

Purpose: Successful clinical trial accrual targeting uncommon genomic alterations will require broad national participation from both National Cancer Institute (NCI)-designated comprehensive cancer centers and community cancer programs. This report describes the initial experience with clinical trial accrual after next-generation sequencing (NGS) from three affiliated non-NCI-designated cancer programs.

Materials And Methods: Clinical trial participation was reviewed after enrollment of the first 200 patients undergoing comprehensive genomic profiling by NGS as part of an institutional intuitional review board-approved protocol at three affiliated hospitals in Rhode Island and was compared with published experience from NCI-designated cancer centers.

Response to Anti-PD-1 Therapy in Metastatic Merkel Cell Carcinoma Metastatic to the Heart and Pancreas.

Metastatic Merkel cell carcinoma (MCC) is a lethal, Merkel cell polyomavirus (MCPyV) cancer with no currently available effective therapy. Harnessing the immune system through an immune checkpoint blockade is an attractive option because the immune system appears to be dysfunctional in the Merkel cell tumor microenvironment. Although MCPyV is expressed in 80% of MCCs and serves as a powerful antigen for stimulating host immune response, intratumoral CD8+ T-cell infiltration is seen only in 18% of MCCs.

Solitary pulmonary nodule: pleuropulmonary synovial sarcoma.

Pleuropulmonary synovial sarcoma (PPSS) is an extremely rare primary malignancy of the lung. We present a case of a middle-aged female with PPSS that was initially discovered as an incidental indeterminate nodule on chest radiograph. Following evaluation with computed tomography (CT), the patient went on to positron-emission tomography (PET)/CT for work-up of the solitary pulmonary nodule, which demonstrated mild FDG-avidity and no other evidence of FDG-avid disease.

Gastric reflux is an independent risk factor for laryngopharyngeal carcinoma.

Background: Gastric reflux can reach into the upper airway, inducing cellular damage in the epithelial lining. This condition is believed to be a risk factor for development of laryngopharyngeal squamous cell carcinoma (LPSCC), although the literature is conflicting.

Methods: To better clarify this relationship, we assessed the association of self-reported heartburn history and medication use among 631 patients with LPSCCs and 1234 control subjects (frequency-matched on age, gender, and town of residence) enrolled as part of a population-based case-control study of head and neck squamous cell carcinoma in the greater Boston area.

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a survival analysis of a Brown University Oncology Group phase II study.

Objectives: To assess the effect on progression-free and overall survival from the addition of cetuximab to paclitaxel-based chemoradiation for patients with squamous cell head and neck cancer from Brown University Oncology Group studies.

Methods: BrUOG HN-204 patients with stage III or IV locally advanced squamous cell cancer of the head and neck without distant organ metastases received 4 weeks of induction cetuximab followed by weekly cetuximab, paclitaxel, carboplatin, and concurrent radiation. Recurrence and survival data were compared with previous Brown University studies utilizing the same paclitaxel-based chemoradiation with and without induction chemotherapy.

A Phase I Study of Dasatinib with Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer.

Objectives: Src family kinases (SFKs) are expressed in non-small cell lung cancer (NSCLC) and may be involved in tumor growth and metastases. Inhibition of SFK may also enhance radiation. The purpose of this study was to evaluate if a maximum dose of 100 mg of dasatinib could be safely administered with concurrent chemoradiation and then continued as maintenance for patients with newly diagnosed stage III NSCLC.

Pathologic response after neoadjuvant carboplatin and weekly paclitaxel for early-stage lung cancer: a Brown University oncology group phase II study.

Introduction: Pathologic complete response (pCR) to neoadjuvant chemotherapy is associated with improved survival in solid tumors. Southwest Oncology Group 9,900 demonstrated a 9% pCR after three cycles of paclitaxel/carboplatin every 21 days. We evaluated pCR rate with intensive weekly paclitaxel in a phase II study.

Carboplatin with weekly docetaxel and ifosfamide in advanced head and neck cancers: a phase I Brown University Oncology Group dose escalation study (HN-93).

Purpose: A phase I study was performed to determine the maximally tolerated dose of carboplatin, ifosfamide, and docetaxel in advanced head and neck cancers.

Methods: Carboplatin (week 1) was administered with weekly docetaxel and ifosfamide for 3 weeks in an every 4-week cycle. Restaging was done after two cycles, while dose level escalation was done in cohorts of three patients.

Pneumonectomy after neoadjuvant chemotherapy and radiation for advanced-stage lung cancer.

Background: Intergroup 0139 Trial suggests an increase in mortality after pneumonectomy in patients receiving preoperative chemotherapy and radiation. We evaluate our outcomes with pneumonectomy after neoadjuvant chemotherapy and radiation.

Methods: Neoadjuvant chemotherapy and radiation consisted of cisplatin 50 mg/m2 on days 1, 8, 29, and 36 and etoposide 50 mg/m2 on days 1-5 and 29-33 given concurrently with 5,040 cGy radiation.

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis.

Objective: To determine the feasibility and toxicity of the addition of cetuximab to paclitaxel, carboplatin, and concurrent radiation for patients with head and neck cancer.

Materials And Methods: Patients with stage III or IV locally advanced squamous cell cancer of the head and neck, without distant organ metastases, were eligible. Patients received 4 weeks of induction cetuximab followed by weekly cetuximab, paclitaxel, carboplatin, and concurrent radiation.

Gefitinib therapy for non-small cell lung cancer.

Gefitinib is a small molecule that specifically inhibits the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) type 1 by interfering with the adenosine triphosphate (ATP) binding site. At doses that maximally inhibit EGFR tyrosine kinase activity chosen for phase II trials, the most common side effects of gefitinib are low-grade rash or diarrhea. An infrequent but serious side effect of gefitinib is interstitial lung disease (ILD).