Bavencio (avelumab)

P2, N=80, Not yet recruiting, American University of Beirut Medical Center

P1/2, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=12 --> 19

P3, N=205, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Nov 2024 --> Feb 2026 | Trial primary completion date: Nov 2024 --> Feb 2026

In this meta-analysis we found that anti-PD1/PD-L1 treatment could be useful in pretreated asMM as they had at least comparable or greater mPFS, mOS, ORR, and DCR than other second-line agents currently being used.

Our study suggests that the targeting of PD-L1 with avelumab alters the expression of CD15 and IL-17RA, which play an important prognostic and therapeutic role in novel anticancer therapy.

P1/2, N=7, Terminated, Fred Hutchinson Cancer Center | Trial completion date: Jan 2025 --> Jan 2024 | Active, not recruiting --> Terminated; Terminated due to insufficient funding

Immune checkpoint inhibitors (ICIs) have shown great success, with FDA-approved drugs like PD-1 inhibitors (Nivolumab, Pembrolizumab, Cemiplimab), PD-L1 inhibitors (Atezolizumab, Durvalumab, Avelumab), and CTLA-4 inhibitors (Ipilimumab, Tremelimumab), alongside LAG-3 inhibitor Relatlimab. This review aims to fill this gap by providing an analysis of the current clinical status of ICIs, emerging biomarkers, mechanisms of resistance, strategies to enhance therapeutic efficacy, and assessment of adverse effects. This review is crucial to furthering our understanding of ICIs and optimizing their application in cancer therapy.

P2, N=70, Not yet recruiting, Groupe Oncologie Radiotherapie Tete et Cou

PD1-L expression, MCC polyomavirus (MCPyV) positivity, and an impaired neutrophil-to-lypmhocyte ratio (NLR) could not be associated with responses to the therapy. Avelumab is an effective and safe drug for the management of advanced MCC, and its effectiveness appears to be impacted by the number and location of metastases.

P2, N=24, Recruiting, University Health Network, Toronto | Trial primary completion date: Jun 2024 --> Dec 2024

P1, N=10, Active, not recruiting, University of Southern California | Recruiting --> Active, not recruiting | N=16 --> 10 | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Aug 2025

A risk score that includes the platelet-to-lymphocyte ratio and lactate dehydrogenase may serve as a useful model for predicting prognosis following the initiation of immune checkpoint inhibitors in patients with metastatic or unresectable urothelial carcinoma.

P=N/A, N=599, Active, not recruiting, Pfizer | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Mar 2025

P1, N=50, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting

Therapeutic antibodies targeting PD-1, such as nivolumab (Opdivo) and pembrolizumab (Keytruda), and PD-L1, including atezolizumab (Tecentriq), durvalumab (Imfinzi), and avelumab (Bavencio) have received FDA approval and are currently being used to treat various cancers. Moreover, we consider the potential role of PD-L1 in the development and pathogenesis of diseases other than cancer, explore PD-L1-focused therapeutic approaches for these diseases, and assess their clinical relevance. Through this review, we hope to provide deeper insights into the PD-L1/PD-1 signaling pathway and present a broad perspective on potential therapeutic approaches for cancer and other diseases.

P2, N=50, Not yet recruiting, Mirror Biologics, Inc. | Trial completion date: Mar 2026 --> Nov 2025

P2, N=0, Withdrawn, EMD Serono Research & Development Institute, Inc. | Not yet recruiting --> Withdrawn | N=70 --> 0

P=N/A, N=300, Recruiting, Astellas Pharma Singapore Pte. Ltd. | Not yet recruiting --> Recruiting

P=N/A, N=300, Completed, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Active, not recruiting --> Completed

P2, N=58, Active, not recruiting, Gruppo Oncologico del Nord-Ovest | Trial completion date: Jul 2024 --> Dec 2024

P1/2, N=173, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=50, Not yet recruiting, Mirror Biologics, Inc. | Trial primary completion date: Dec 2025 --> Mar 2026

Three weeks after initiating maintenance use of a PD-L1 inhibitor, avelumab, a massive amount of metastases developed, leading to the patient's demise. Omics analysis, utilizing metastatic tissues obtained from an immediate autopsy, implied the contribution of M2 macrophages, TGF-β signaling, and interleukin-8 to HPD pathogenesis.

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Jul 2024 --> Mar 2025

We report the results of the REGOMUNE phase II study, in which Caucasian patients were administered regorafenib, a multi-tyrosine kinase inhibitor, in combination with avelumab, a PD-L1-targeting monoclonal antibody. Additionally, peripheral biomarker assessments identified elevated levels of cytokines, including CSF-1, IL-4, IL-8, and TWEAK, correlating with adverse clinical outcomes, thereby accentuating the role of macrophage infiltration in mediating resistance. These insights furnish an invaluable foundation for elucidating, and potentially circumventing, resistance mechanisms in current AGC therapeutic paradigms, emphasizing the integral role of tumor microenvironmental dynamics and immune modulation.

Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed.

These novel combinations are revolutionizing the treatment standard for metastatic urothelial carcinoma and necessitate a new approach to managing side effects.

The rapidly expanding class of therapies targeting immune checkpoints for the treatment of various cancers now includes 8 clinically approved agents: a lymphocyte-activation gene 3 (LAG-3) inhibitor (relatlimab), a cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitor (ipilimumab), three programmed cell death protein 1 (PD-1) inhibitors (nivolumab, pembrolizumab and cemiplimab), and three programmed cell death ligand-1 (PD-L1) inhibitors (atezolizumab, durvalumab, and avelumab). Previously, we reviewed the mechanisms of immune-related adverse events (irAEs), strategies for management of irAEs, and highlighted similarities as well as differences amongst clinical guidelines from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), Society for Immunotherapy of Cancer (SITC), and European Society for Medical Oncology (ESMO). Herein, we provide an update that includes discussion of changes to these clinical guidelines since our last review, the new LAG-3 targeted agents, emerging patterns of irAEs, and new directions for improved monitoring and treatment of irAEs that could incorporate interdisciplinary pharmacist-led teams, artificial intelligence, and pharmacogenomics.

P2, N=827, Recruiting, Gilead Sciences | Trial completion date: Jul 2026 --> Jun 2030 | Trial primary completion date: Jul 2024 --> Jun 2030

P2; Active, not recruiting --> Completed

The hypothesis that induction avelumab could enhance the efficacy of subsequent ChT was not proven. Administering IO alone as induction before ChT is not an adequate strategy.

P1, N=22, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=32 --> 22

P1/2, N=3, Terminated, ImmunityBio, Inc. | Phase classification: P1b/2 --> P1/2 | N=173 --> 3 | Unknown status --> Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

P=N/A, N=106, Completed, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Jun 2024

P2, N=147, Active, not recruiting, ImmunityBio, Inc. | Phase classification: P2b --> P2 | Trial completion date: Dec 2024 --> Dec 2030 | Trial primary completion date: May 2024 --> Aug 2029

The presence of irAEs under ICI therapy in patients with mRCC is associated with better PFS and OS. Thus, manageable irAEs should not be cause for premature discontinuation of ICI therapy, as they seem to indicate favorable outcomes. Considering the time-dependent nature of irAEs is crucial estimating their value as predictive markers.

P2, N=50, Not yet recruiting, Mirror Biologics, Inc.

P1/2, N=25, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Dec 2025

P1/2, N=9, Terminated, ImmunityBio, Inc. | N=79 --> 9 | Trial completion date: Oct 2023 --> Jan 2024 | Active, not recruiting --> Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

P2, N=50, Recruiting, Centre Francois Baclesse | Trial completion date: Dec 2023 --> Dec 2025

Median overall survival (OS) ranged from 12.1 to 31.5 months across the studies, with the combination of enfortumab vedotin and pembrolizumab demonstrating the most substantial reduction in the risk of death (HR 0.47 [95% CrI: 0.38, 0.58]), followed by avelumab monotherapy (HR 0.69 [95% CrI: 0.56, 0.86]). Avelumab showed notable single-agent activity. These findings provide a valuable framework to guide clinical decision-making and highlight priority areas for future research, including biomarker refinement and novel combination strategies to enhance antitumor immunity in this challenging malignancy.

P1/2, N=4, Terminated, ImmunityBio, Inc. | N=65 --> 4 | Unknown status --> Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention