Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial.

GT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a "3 + 3" schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103.

Real-World Treatment Patterns and Clinical Outcomes in Patients With Locally Advanced or Metastatic Urothelial Carcinoma by Eligibility for Maintenance Avelumab.

Introduction: 1L PBC has historically been recommended for patients with la/mUC. Maintenance avelumab is recommended for patients without disease progression following 1L PBC. Real-world data on the proportion of patients eligible for maintenance avelumab are limited, and outcomes among patients ineligible for maintenance avelumab are uncertain.

Correlation of safety and efficacy of atezolizumab therapy across indications.

Background: The association between safety and efficacy of immune checkpoint inhibitors is known, but the correlation between severity and impact of specific organ involvement by immune-related adverse events (irAE) and cancer outcomes is poorly understood. Most irAEs are mild-to-moderate but severe irAEs may pose clinical management challenges and affect patient outcomes.

Methods: We assessed the association between irAE grade (G) and specific organ involvement with overall survival (OS) in 9,521 patients across 14 studies involving atezolizumab as mono (IO) or with chemo/targeted (C-IO) therapy as compared with chemo/targeted therapy (C) in advanced non-small cell lung, small-cell lung, renal cell, urothelial, and triple-negative breast cancers.

Eligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer.

Background: Trimodality therapy (TMT) is a viable option for muscle-invasive localized bladder cancer, providing an alternative to radical cystectomy in properly selected patients. The approval of novel therapeutics in different stages of bladder cancer treatment has sparked interest in exploring concurrent systemic therapies with radiation in clinical trials to enhance long-term outcomes. Achieving uniformity in trial eligibility criteria and endpoint definitions is imperative in describing clinical significance, comparing trials, and changing standard of care guidelines.

Adjuvant immunotherapy in high-risk muscle invasive urothelial carcinoma: A systematic review and meta-analysis of randomized clinical trials.

Despite surgical resection, many patients with muscle invasive urothelial carcinoma (MIUC) experience recurrence. Adjuvant immune checkpoint inhibition (ICI) following radical resection in patients with MIUC demonstrates disparate outcomes among phase III randomized controlled trials (RCTs). Our objective was to synthesize available data regarding the disease-free survival (DFS) benefit of adjuvant ICIs for patients with MIUC and evaluate the overall safety profile of ICIs in this setting.

Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma.

Background: Muscle-invasive urothelial carcinoma is an aggressive disease with high rates of relapse. Whether pembrolizumab as adjuvant therapy would be effective in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery is unknown.

Methods: In this phase 3 trial, we randomly assigned patients, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks for 1 year or to undergo observation.

Mismatch repair deficiency and microsatellite instability in urothelial carcinoma: a systematic review and meta-analysis.

Background: Mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) occur in a subset of cancers and have been shown to confer sensitivity to immune checkpoint inhibition (ICI); however, there is a lack of prospective data in urothelial carcinoma (UC).

Methods And Analysis: We performed a systematic review to estimate the prevalence of dMMR and MSI-H in UC, including survival and clinical outcomes. We searched for studies published up to 26 October 2022 in major scientific databases.

Approaches to Treating High Risk and Advanced Renal Cell Carcinoma (RCC): Key Trial Data That Impacts Treatment Decisions in the Clinic.

The treatment paradigm for high risk localized and advanced kidney cancer has been characterized by ongoing changes, with the introduction of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and later with immune checkpoint blockade. In this article, we review how current evidence informs our decision-making on post-checkpoint inhibitor systemic therapies, the role of adjuvant and/or neoadjuvant therapies, and the role of cytoreductive nephrectomy in the evolving systemic therapy landscape. While some studies support a post-checkpoint inhibitor benefit from the VEGFR TKIs cabozantinib or axitinib, the benefit of doublet therapies including a VEGF receptor inhibitor and a checkpoint inhibitor remains an area of active investigation, with the combination of lenvatinib plus pembrolizumab showing promise but with a Phase III trial of the combination of atezolizumab plus cabozantinib showing no benefit over cabozantinib alone.

Vaccine approaches to treat urothelial cancer.

Bladder cancer (BC) accounts for about 4% of all malignancies. Non-muscle-invasive BC, 75% of cases, is treated with transurethral resection and adjuvant intravesical instillation, while muscle-invasive BC warrants cisplatin-based perioperative chemotherapy. Although immune-checkpoint inhibitors, antibody drug conjugates and targeted agents have provided dramatic advances, metastatic BC remains a generally incurable disease and clinical trials continue to vigorously evaluate novel molecules.

Impact of Angiotensin Converting Enzyme Inhibitors on Pathologic Complete Response With Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer.

Introduction: The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. We examined the association of RAS inhibitors (RASi)-namely angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB)-with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) preceding radical cystectomy (RC).

Patients And Methods: We retrospectively investigated concurrent RASi use with NAC prior to RC in 302 patients with MIBC from 3 academic institutions.

New Therapeutic Horizons for Advanced or Metastatic Penile Cancer.

Penile cancer is a rare malignancy with a poor prognosis. Studies with single-agent immune checkpoint inhibitors (ICIs) have demonstrated efficacy, but response rates are low. Studies combining ICIs with both chemotherapy and targeted therapy are ongoing.

Factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma: A retrospective multicentre cohort study.

Background: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis.

Objectives: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy.

Real-World Multicenter Study of PD-1 Blockade in HIV-Associated Classical Hodgkin Lymphoma Across the United States.

Background: Despite a higher risk of classical Hodgkin lymphoma (cHL) in people with HIV and the demonstrated safety and efficacy of PD-1 blockade in cHL, there are limited data on the use of these agents in HIV-associated cHL (HIV-cHL).

Patients/methods: We retrospectively identified patients with HIV-cHL from the "Cancer Therapy using Checkpoint inhibitors in People with HIV-International (CATCH-IT)" database who received nivolumab or pembrolizumab, alone or in combination with other agents, and reviewed records for demographics, disease characteristics, immune-mediated adverse events (imAEs), and treatment outcomes. Changes in CD4 T-cell counts with treatment were measured via Wilcoxon signed-rank tests.

The evolving treatment landscape of metastatic urothelial cancer.

Cisplatin-based chemotherapy is currently the first-line standard of care for patients with metastatic urothelial cancer (mUC); however, up to 50% of patients are ineligible for cisplatin, necessitating alternative treatment options. Immune checkpoint inhibitors have been shown to be effective in cisplatin-ineligible patients. However, despite advances in the first-line setting, the prognosis remains poor, and challenges persist in selecting optimal therapies, treatment sequences and combination regimens.

Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy.

Background And Objective: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL).

Methods: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation.

Comprehensive multiplexed autoantibody profiling of patients with advanced urothelial cancer.

Background: Comprehensive profiling of autoantibodies (AAbs) in metastatic urothelial cancer (mUC) has not been performed to date. This may aid in diagnosis of UC, uncover novel therapeutic targets in this disease as well as identify associations between AAbs and response and toxicity to systemic therapies.

Methods: We used serum from patients with mUC collected prior to and after systemic therapy (immune checkpoint inhibitor (ICI) or platinum-based chemotherapy (PBC)) at Dana-Farber Cancer Institute.

Comparative real-world survival outcomes of muscle-invasive bladder cancer treated with bladder-only vs. whole-pelvis concurrent chemoradiation.

Introduction: Elective pelvic nodal irradiation for patients with muscle-invasive bladder cancer (MIBC) undergoing trimodal therapy (TMT ) is controversial. In patients with node-negative (N0) MIBC, the benefit of elective whole-pelvis concurrent chemoradiation (WP-CCR) compared to bladder-only (BO )-CCR has not been demonstrated. Using real-world data from the National Cancer Database (NCDB ), we sought to compare the overall survival (OS ) between BO-CCR and WP-CCR for MIBC.