Tecentriq (atezolizumab)

We performed a comprehensive evaluation of liver-metastatic (LM) disease among mCRC patients enrolled in the phase II randomized AtezoTRIBE trial, that showed a modest benefit from the addition of atezolizumab (atezo) to 1st line FOLFOXIRI/bevacizumab (bev) and identified Immunoscore IC as a predictor of ICI efficacy in the proficient mismatch repair (pMMR) population... In our cohort of pMMR mCRC patients, the immune microenvironment of tumors with LM spread does not differ from that of tumors with no liver involvement. The presence or not of LM disease does not affect the efficacy of adding atezo to first-line FOLFOXIRI/bev, differently than Immunoscore IC.

We demonstrated that FOXA1 prevents tumor immune evasion by inhibiting IFN-γ induced PD-L1 expression in NPC cells. Our research findings provide new insights into the immunotherapeutic biomarkers and targets for NPC, which is important for the clinical application of programmed cell death protein-1/PD-L1 antibodies in NPC.

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.

P2, N=110, Active, not recruiting, University of Oklahoma | Trial primary completion date: Aug 2024 --> Feb 2025

P2, N=45, Not yet recruiting, European Institute of Oncology

Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

P2, N=210, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

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

P4, N=97, Recruiting, The First Affiliated Hospital of USTC (Anhui Provincial Hospital); The First Affiliated Hospital of USTC (Anhui Provincial Hospital)

P2, N=208, Not yet recruiting, Western Sydney Local Health District

P1/2, N=340, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Oct 2026 --> Jan 2025 | Trial primary completion date: Oct 2025 --> Jan 2025

P3, N=740, Not yet recruiting, Tempest Therapeutics

P3, N=595, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

P1, N=24, Active, not recruiting, Imugene Limited | Trial completion date: Mar 2026 --> May 2025 | Trial primary completion date: Feb 2026 --> Nov 2024

P=N/A, N=518, Completed, Intergroupe Francophone de Cancerologie Thoracique | Trial completion date: Nov 2021 --> Sep 2024

Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.

P1, N=272, Active, not recruiting, Genentech, Inc. | Trial completion date: Nov 2024 --> Mar 2025 | Trial primary completion date: Nov 2024 --> Mar 2025

P2, N=96, Completed, Queen Mary University of London | Unknown status --> Completed

P2, N=123, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Oct 2024 --> Feb 2025

P2, N=58, Recruiting, Queen Mary University of London | Trial completion date: Dec 2024 --> May 2026 | Trial primary completion date: Jul 2023 --> May 2026

P2, N=88, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> May 2025 | Trial primary completion date: Jan 2025 --> May 2025

P2, N=416, Completed, Palleos Healthcare GmbH | Active, not recruiting --> Completed

P3, N=56, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | N=1150 --> 56 | Trial completion date: Jun 2039 --> Dec 2025 | Trial primary completion date: Mar 2034 --> Dec 2025

P2/3, N=1000, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1, N=61, Completed, invoX Pharma Limited | Active, not recruiting --> Completed | N=146 --> 61 | Trial completion date: Dec 2024 --> Jul 2024 | Trial primary completion date: Dec 2024 --> Jul 2024

A total of 125 ES-SCLC patients undergoing atezolizumab and 161 patients undergoing ICI as first-line treatment were recruited from IMpower133 and shanzhong cohort...Those harboring <4 metastatic sites had fewer M2 macrophage and more CD4 naïve T cells infiltration, which was further confirmed by mIF of ES-SCLC samples from shanzhong cohort. Our study provides rationale for ICI rechallenge among ES-SCLC patients with <4 metastatic sites, suggesting beneficial outcome by reshaping TME.

P1, N=3, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=21 --> 3

89Zr-DFO-Atezolizumab can visualize distinct PD-L1 expression levels with high specificity in preclinical mouse models and in patients with GBM, whilst complementing ex vivo analysis.

P2, N=142, Not yet recruiting, Gruppo Oncologico Italiano di Ricerca Clinica

P2, N=172, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

P2, N=100, Recruiting, Nasser Hanna | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

P1, N=422, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Apr 2026 --> Nov 2029 | Trial primary completion date: Sep 2025 --> Aug 2027 | Recruiting --> Active, not recruiting

P1, N=250, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting

Patients with higher frequencies of CD8+PD-1+Ki-67+ T cells experienced significantly improved overall survival, while those with lower frequencies of CD4+Foxp3+PD-1+LAG3+ T cells also had notable survival benefits. These findings enhance the overall understanding of immune responses to this combination therapy, facilitating improved patient stratification and personalized therapeutic approaches for HCC.

Furthermore, a multivariable analysis revealed that increased levels of IL-10 and TNF-α were significant predictors of enhanced survival (hazard ratio, 0.07; 95% confidence interval, 0.01-0.46; p = 0.005). An early increases in IL-10 and TNF-α after Ate/Bev treatment may serve as effective biomarkers for clinical outcomes in advanced HCC patients.

Atez/Bev-TACE sequential therapy improved prognosis compared with Atez/Bev monotherapy in patients with intermediate-stage HCC. Moreover, Atez/Bev should be readministered after TACE.

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.

Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS. ClinicalTrials.gov Identifier: NCT03181100.

P1, N=63, Active, not recruiting, Adlai Nortye Biopharma Co., Ltd. | Trial primary completion date: Sep 2024 --> Dec 2024

P1/2, N=138, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

Implementing RSAs can optimize resource allocation, making IO treatment more accessible, especially in low-income countries.

On the order of 20% of NSCLCs bear activating mutations in EGFR and are treated with osimertinib and other kinase antagonists...Local treatment options to control thoracic disease include radiotherapy and surgery. In patients with extensive-stage disease, a platinum agent (cisplatin or carboplatin) combined with etoposide and an anti-PDL1 inhibitor (atezolizumab or durvalumab) for four cycles followed by anti-PDL1 maintenance therapy is the recommended first-line regimen.