Bavencio (avelumab)

P1, N=16, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Aug 2024

P2, N=25, Recruiting, Panagiotis Konstantinopoulos, MD, PhD | Not yet recruiting --> Recruiting

P1, N=325, Active, not recruiting, Exelixis | Trial completion date: Nov 2024 --> May 2027 | Trial primary completion date: Nov 2024 --> Aug 2026

The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.

These preliminary findings suggest that evaluation of in vitro cytotoxicity together with CD107a expression in mCRC patients derived PBMC could be a useful tool to identify early responders after only 8 weeks of treatment with cetuximab plus avelumab. In addition, we aim to further investigate the potential role of CCL5 secreted by peripheral immune cells and its cut-off as a predictive biomarker of mCRC progression in a larger cohort of patients.

These monoclonal antibodies target immune checkpoints, including cytotoxic T-lymphocyte-associated protein 4 (ipilimumab and tremelimumab), programmed death 1 (nivolumab, pembrolizumab, cemiplimab, and dostarlimab), programmed death ligand 1 (atezolizumab, avelumab, and durvalumab), and lymphocyte activation gene 3 (relatlimab), and effectively augment the immune response against tumor cells. Despite clinical improvements with immunomodulatory therapy, with corticosteroids the mainstay of treatment, mortality remains high, particularly in those with associated myocarditis or respiratory failure requiring intubation, where mortality occurs in up to 50%. ICI withdrawal can lead to cancer progression and death, highlighting a need for improved approaches to ICI rechallenge, performed in limited patients with variable success to date.

P1/2, N=101, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

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.

Efficacy of avelumab for high-risk TNBC did not significantly differ by PD-L1 in the ITT, or by TILs and RCB in Stratum B. However, these biomarkers help identifying subgroups of patients at poorer prognosis deriving the greatest magnitude of benefit from this treatment.

This is a phase 2 pilot study including pts with stage II/III ER-positive/HER2-negative breast cancer who were randomized 2:1 to receive ET (aromatase inhibitors for post-menopausal pts; tamoxifen+/-ovarian function suppression for pre-menopausal pts) with avelumab, with or without palbo (palbo vs. control arms). Responses in the ImmunoADAPT study were largely restricted to the ET+avelumab+palbo arm; lobular histology, lower tumor grade and sTILs <1% demonstrated a trend towards improved responses. None of the pts with high ODx/MMP responded. These observations require further investigation to understand the individual contributions of treatment and biological changes to the TME; serial IMC and ST data will be presented at the meeting.

Methods The PACE (NCT03147287) multicenter phase II trial randomized 220 pts with ER+, HER2- MBC who had progressed on at least 6 months (mo) of prior CDK4/6i and aromatase inhibitor (AI) to receive fulvestrant alone (F), F plus palbociclib (F+P), or F+P plus the PD-1 inhibitor avelumab (F+P+A). However, high C2D1 on-treatment TKa was associated with inferior outcomes. Early dynamic changes in TKa levels may allow identification of populations with distinct prognoses, possibly facilitating clinical decisions in this context.

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