An expanded safety/feasibility study of the EMulate Therapeutics Voyager™ System in patients with recurrent glioblastoma.

The EMulate Therapeutics Voyager™ is a simple, wearable, home-use device that uses an alternating electromagnetic field to alter biologic signaling within cells. To assess the safety/feasibility of the Voyager in the treatment of recurrent glioblastoma (rGBM). In this study, patients with rGBM were treated with Voyager as monotherapy or in combination with standard chemotherapy at the Investigator's discretion.

Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with human papillomavirus-associated malignancies.

Background: Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor (TGF)-βRII (a TGF-β 'trap') fused to a human IgG1 mAb blocking programmed cell death ligand 1. This is the largest analysis of patients with advanced, pretreated human papillomavirus (HPV)-associated malignancies treated with bintrafusp alfa.

Methods: In these phase 1 (NCT02517398) and phase 2 trials (NCT03427411), 59 patients with advanced, pretreated, checkpoint inhibitor-naive HPV-associated cancers received bintrafusp alfa intravenously every 2 weeks until progressive disease, unacceptable toxicity, or withdrawal.

Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study.

Introduction: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).

Methods: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks.

Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squamous cell carcinoma of the head and neck: results from a phase I cohort.

Background: We report the clinical activity and safety of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β)RII receptor (a TGF-β 'trap') fused to a human IgG1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), in patients with heavily pretreated squamous cell carcinoma of the head and neck (SCCHN).

Methods: In this phase I dose-expansion cohort, patients with advanced SCCHN not amenable to curative therapy that progressed/recurred after platinum therapy in the recurrent/metastatic setting, or <6 months after platinum therapy in the locally advanced setting, received bintrafusp alfa 1200 mg intravenously every 2 weeks. The primary endpoint was confirmed best overall response (BOR; Response Evaluation Criteria for Solid Tumors (RECIST) 1.

PSMA ADC monotherapy in patients with progressive metastatic castration-resistant prostate cancer following abiraterone and/or enzalutamide: Efficacy and safety in open-label single-arm phase 2 study.

Background: Prostate-specific membrane antigen (PSMA) is a well-established therapeutic and diagnostic target overexpressed in both primary and metastatic prostate cancers. PSMA antibody-drug conjugate (PSMA ADC) is a fully human immunoglobulin G1 anti-PSMA monoclonal antibody conjugated to monomethylauristatin E, which binds to PSMA-positive cells and induces cytotoxicity. In a phase 1 study, PSMA ADC was well tolerated and demonstrated activity as measured by reductions in serum prostate-specific antigen (PSA) and circulating tumor cells (CTCs).

First-in-human study of TK-positive oncolytic vaccinia virus delivered by adipose stromal vascular fraction cells.

Background: ACAM2000, a thymidine kinase (TK)-positive strain of vaccinia virus, is the current smallpox vaccine in the US. Preclinical testing demonstrated potent oncolytic activity of ACAM2000 against several tumor types. This Phase I clinical trial of ACAM2000 delivered by autologous adipose stromal vascular fraction (SVF) cells was conducted to determine the safety and feasibility of such a treatment in patients with advanced solid tumors or acute myeloid leukemia (AML).

Patient-specific dendritic cell vaccines with autologous tumor antigens in 72 patients with metastatic melanoma.

Aim: Metastatic melanoma patients were treated with patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated cells from short-term autologous tumor cell lines.

Patients & Methods: A total of 72 patients were enrolled in a single-arm Phase I/II (NCT00948480) trial or a randomized Phase II (NCT00436930).

Results: Toxicity was minimal.

Phase 1 study of PSMA ADC, an antibody-drug conjugate targeting prostate-specific membrane antigen, in chemotherapy-refractory prostate cancer.

Background: Prostate-specific membrane antigen (PSMA) is a well-characterized target that is overexpressed selectively on prostate cancer cells. PSMA antibody-drug conjugate (ADC) is a fully human IgG1 monoclonal antibody conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE), which is designed to specifically bind PSMA-positive cells, internalize, and then release its cytotoxic payload into the cells. PSMA ADC has demonstrated potent and selective antitumor activity in preclinical models of advanced prostate cancer.

An early feasibility study of the Nativis Voyager device in patients with recurrent glioblastoma: first cohort in US.

Aim: Evaluation of the Nativis Voyager device in patients with recurrent glioblastoma (rGBM).

Materials & Methods: Voyager is a noninvasive, nonthermal, nonionizing and portable investigational device which delivers ultra-low radio frequency energy (ulRFE) that uses a magnetic field to penetrate tissues to alter specific biologic functions within cells. Patients with rGBM were treated with Voyager alone (V) or Voyager in combination with standard of care (V + SoC).

Randomized phase II trial of autologous dendritic cell vaccines versus autologous tumor cell vaccines in metastatic melanoma: 5-year follow up and additional analyses.

Background: Despite improved survival following checkpoint inhibitors, there is still a potential role for anti-cancer therapeutic vaccines. Because of biological heterogeneity and neoantigens resulting from each patient's mutanome, autologous tumor may be the best source of tumor-associated antigens (TAA) for vaccines. Ex vivo loading of autologous dendritic cells with TAA may be associated with superior clinical outcome compared to injecting irradiated autologous tumor cells.

Phase I single dose, two-period and two-sequence cross-over trial to evaluate the relative bioavailability of two oral pimasertib formulations in advanced cancer patients.

Purpose: A phase I two-period two sequence cross-over study compared the bioavailability of two pimasertib (MSC1936369B/AS703026) formulations (capsule versus tablet) in advanced cancer patients.

Methods: Patients with advanced solid tumors were randomized to one of two treatment sequences utilizing pimasertib tablet (test; 3 × 20 mg, PO QD) and capsule (standard; 2 × 30 mg, PO QD). The trial comprised a screening and baseline period, two time periods or parts A and B, and a trial extension phase.

Dendritic Versus Tumor Cell Presentation of Autologous Tumor Antigens for Active Specific Immunotherapy in Metastatic Melanoma: Impact on Long-Term Survival by Extent of Disease at the Time of Treatment.

In patients with metastatic melanoma, sequential single-arm and randomized phase II trials with a therapeutic vaccine consisting of autologous dendritic cells (DCs) loaded with antigens from self-renewing, proliferating, irradiated autologous tumor cells (DC-TC) showed superior survival compared with similar patients immunized with irradiated tumor cells (TC). We wished to determine whether this difference was evident in cohorts who at the time of treatment had (1) no evidence of disease (NED) or (2) had detectable disease. Eligibility criteria and treatment schedules were the same for all three trials.

Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients.

Purpose. Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization.

Tumor stem cell antigens as consolidative active specific immunotherapy: a randomized phase II trial of dendritic cells versus tumor cells in patients with metastatic melanoma.

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products.

Differences in clinical trial patient attributes and outcomes according to enrollment setting.

Purpose: During the last 25 years, National Cancer Institute (NCI) cooperative trial groups have extended trial networks from academic centers to include certain community and Veterans Health Administration (VHA) centers. We compared trial patients' attributes and outcomes by these enrollment settings.

Patients And Methods: Studying 2,708 patients on one of 10 cooperative group, randomized lung trials at 272 institutions, we compared patient attributes by enrollment setting (ie, academic, community, and VHA affiliates).

Phase II trial of dendritic cells loaded with antigens from self-renewing, proliferating autologous tumor cells as patient-specific antitumor vaccines in patients with metastatic melanoma: final report.

Unlabelled: Between January 2001 and September 2007, we treated 54 metastatic melanoma patients with patient-specific tumor cell vaccines consisting of dendritic cells (DCS), derived from their peripheral blood cells that were cultured in interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor (GM-CSF), which had phagocytosed irradiated autologous tumor cells from a continuously proliferating, self-renewing, autologus tumor cell (TC) culture. The loaded DCs were injected subcutaneously in 500 microg of GM-CSF weekly x three, and then monthly for 5 months, for a total of up to 8 injections. The 34 men and 20 women had a median age of 50.

Interruptions of once-daily thoracic radiotherapy do not correlate with outcomes in limited stage small cell lung cancer: analysis of CALGB phase III trial 9235.

Purpose: Retrospective data suggests prolonging the time to complete thoracic radiotherapy (TRT) may negatively impact tumor control and survival in limited stage small cell lung cancer (LSCLC). We examined the association between TRT duration and outcomes on a prospective phase III study.

Material And Methods: This review included 267 patients who received protocol TRT on a phase III CALGB LSCLC study assessing the addition of tamoxifen to standard chemo-radiotherapy.

Phase I/II study of IV topotecan in combination with whole brain radiation for the treatment of brain metastases.

A phase I/II trial was conducted to determine the toxicities and efficacy (overall response, overall survival, and progression-free survival) of the combination of topotecan and whole brain radiation therapy (XRT) in patients with brain metastases. Patients received 30 Gy XRT given in 10 fractions to the whole brain. In phase I, patients were treated in groups of three at each topotecan dose level; dose escalation proceeded until the maximum tolerated dose (MTD) was identified.

A phase III trial evaluating the combination of cisplatin, etoposide, and radiation therapy with or without tamoxifen in patients with limited-stage small cell lung cancer: Cancer and Leukemia Group B Study (9235).

Based on both clinical and laboratory data that suggested that tamoxifen (TAM) enhanced the effectiveness of cisplatin (DDP)-based chemotherapy regimens, the Cancer and Leukemia Group B (CALGB) designed and initiated a prospective, randomized phase III trial to test the efficacy of the addition of high-dose TAM to a standard chemoradiation regimen of DDP and etoposide (VP-16) in patients with limited-stage small cell lung cancer (LS-SCLC). Between August 6, 1993, and January 15, 1999, 319 patients with LSSCLC were accrued to CALGB 9235. Patients were randomized to receive chemotherapy with or without high-dose TAM.

Phase I/II trial of melanoma patient-specific vaccine of proliferating autologous tumor cells, dendritic cells, and GM-CSF: planned interim analysis.

Aim: The aim of this study was to investigate the feasibility, safety, and clinical efficacy of patient-specific dendritic cell vaccines in patients with metastatic melanoma. A planned interim analysis was conducted on the first 20 patients.

Methods: Tumor cell lines were established from metastatic tumor, expanded to 200 million cells, and then incubated with interferon-gamma for patients who were candidates for therapy.

Systemic chemotherapy for the treatment of metastatic melanoma.

The role of systemic chemotherapy in the treatment of patients with metastatic melanoma remains of questionable benefit. Despite encouraging phase II data from multiple institutions that suggested an improved overall response rate for patients treated with the Dartmouth regimen, recently completed phase III trials have failed to demonstrate a significant benefit in survival. Of concern is the fact that there have been relatively few new chemotherapeutic agents in the past several years that have demonstrated any activity in this disease.

Metastatic melanoma in a patient with Clouston syndrome successfully treated with isolated hyperthermic limb perfusion.

Background: Clouston syndrome is an autosomal dominant disorder characterized by nail dystrophy, partial or total alopecia, and hyperkeratosis of the palms and soles.

Objective: Although a variety of unusual cutaneous manifestations have been described, the incidence of melanoma in this population is unknown.

Methods: This article reports a case of in-transit metastatic subungual melanoma in a patient with Clouston syndrome successfully treated with hyperthermic limb perfusion with melphalan.