Avastin (bevacizumab)

Background : Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with recurrent IDHwt-glioblastoma (rGBM). The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of recurrent glioblastoma patients responding to specific second-line treatment with bevacizumab or regorafenib or nitrosoureas.

Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of pTEN in these patient populations.

The LIBImAb Study is a phase III, randomized, openlabel, comparative, multi-center trial to assess the superiority in terms of efficacy of bevacizumab versus cetuximab in combination with FOLFIRI in mCRC pts, RAS/BRAFwt on tumor tissue and RAS/BRAF mutant (RAS/BRAFmut) at liquid biopsy... These data indicate the feasibility of cfDNA-based prospective enrolment in an interventional trial using a test with a rapid TAT for screening of RAS/ BRAF status in plasma. Our preliminary findings also suggest that ctDNA testing might better recapitulate the tumor heterogeneity of mCRC pts thus complementing tissue genomic profiling.

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.

The overall prognosis of BRAF V600E mutant mCRC patients is poor. Poor differentiation and liver metastases were negative independent prognostic factors for OS. First-line triplet-drug therapy was associated with better OS, especially in patients with good physical condition and high tumor burden.

This article critically reviews the large body of literature on these issues, highlighting those contributions that describe the molecular mechanisms, thus expanding our understanding of the VEGF-virus interactions in disease and therapy. This could facilitate the clinical use of therapeutic virus vectors in precision medicine for the VEGF system.

A detail estimation of KRASG12D mut mCRC patients' characteristics and expected outcomes may be useful when planning future studies in this subgroup. The high prevalence of PI3K/PTEN/Akt pathway activating alterations may affect the efficacy of targeted strategies.

These results indicate marked heterogeneity of expression of metabolism-associated markers in ovarian cancer; however, there was a lack of association with clinical benefit after chemotherapy/anti-vascular endothelial growth factor treatment. Notwithstanding the lack of prognostic value, knowledge of the pattern of expression of these biomarkers in tumors can be useful for patient stratification purposes when new drugs targeting these metabolic pathways will be tested.

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

P3, N=42, Completed, North Eastern German Society of Gynaecological Oncology | Active, not recruiting --> Completed | N=190 --> 42 | Trial completion date: Jan 2025 --> Jul 2024

Firstly, we describe the patient's treatment history, including failed third-line combination treatments of systemic chemotherapy with bevacizumab or carrelizumab or anlotinib, primary lung tumor recurrence, bilateral lung metastases progression, and new brain metastatic lesion detection. Next, we detail the patient's fourth-line treatment with radiotherapy for brain metastases and two cycles of bevacizumab plus Abraxane and cisplatin, however, the disease progressed and relapsed...However, the patient died due to hypoproteinemia combined with severe pneumonia in December 2023. Furmonertinib may be effective for NSCLC patients with HER2 T8962A and L869R mutations and further studies are needed to confirm these results in prospective clinical trials.

P1/2, N=162, Recruiting, Bristol-Myers Squibb | Trial primary completion date: Jun 2024 --> Oct 2025

We aim to assess the addition of XB2001 (anti-IL-1 alpha monoclonal antibody) plus trifluridine/tipiracil-bevacizumab in mCRC refractory to standard chemotherapy. This multicenter, randomized, double blind, non-comparative Phase I-II study (ClinicalTrials.gov NCT05201352) will assess the efficacy and safety of trifluridine/tipiracil-bevacizumab and XB2001 in patients with mCRC previously treated for metastatic disease by chemotherapy treatment including oxaliplatin, irinotecan, 5-FU, antiangiogenic and/or anti-EGFR if indicated...Primary end point of Phase II is the efficacy of trifluridine/tipiracil-bevacizumab + XB2001 in term of 6-month overall survival. Ancillary analysis will be performed.

For patients with advanced EGFR-mutant NSCLC, osimertinib plus bevacizumab has some clinical benefit compared with osimertinib alone. Still, it does not provide additional long-term survival benefits and has higher toxicity. More well-designed, multicenter RCTs are needed to identify the subgroups of patients most likely to benefit from this combination regimen and to validate the optimal dose of this combination regimen.

P2, N=83, Active, not recruiting, Vejle Hospital | Recruiting --> Active, not recruiting | Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025

P3, N=32, Recruiting, NaviFUS Corporation | Not yet recruiting --> Recruiting

P2/3, N=40, Completed, Sun Yat-sen University | Not yet recruiting --> Completed | N=30 --> 40 | Trial completion date: Mar 2025 --> May 2024 | Trial primary completion date: Mar 2025 --> Mar 2024

P3, N=560, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting

The FDA (US Food and Drug Administration) has approved olaparib as a front-line maintenance therapy in combination with bevacizumab for patients with newly diagnosed advanced ovarian, fallopian tube, or primary peritoneal cancer with HRD+ status. We have demonstrated that the TSO500-HRD assay can accurately determine HRD status in ovarian tumors.

P4, N=20, Recruiting, yangjianjun | Initiation date: Jan 2024 --> Sep 2024

P1, N=50, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

P2, N=118, Not yet recruiting, Beijing Biostar Pharmaceuticals Co., Ltd.

P1/2, N=100, Completed, Enterome | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Mar 2024 | Trial primary completion date: Dec 2024 --> Jan 2024

P=N/A, N=20, Not yet recruiting, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Renji Hospital, School of Medicine, Shanghai Jiao Tong University

P4, N=50, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University of

P4, N=100, Not yet recruiting, Anhui Chest Hospital; Anhui Chest Hospital

P2, N=40, Not yet recruiting, Affiliated Cancer Hospital of Shandong First Medical University; Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandon

P2, N=40, Not yet recruiting, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences.; Peking Union Medical College Hospital, Chinese Academy of Medical Science

P2, N=37, Not yet recruiting, Shanghai East Hospital; Shanghai East Hospital

P2, N=36, Not yet recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

P2, N=50, Not yet recruiting, The First Affiliated Hospital of Guangxi Medical University; The First Affiliated Hospital of Guangxi Medical University

P1, N=20, Not yet recruiting, Zhongshan Hospital; Zhongshan 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

P2, N=72, Not yet recruiting, Coherus Biosciences, Inc.

P2, N=94, Recruiting, Vall d'Hebron Institute of Oncology | Not yet recruiting --> Recruiting

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

P1/2, N=40, Not yet recruiting, Pardis Noor Medical Imaging and Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Initiation date: Apr 2024 --> Apr 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=58, Recruiting, Sutro Biopharma, Inc. | Active, not recruiting --> Recruiting

P1/2, N=51, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Jan 2025 --> May 2025 | Trial primary completion date: Jan 2025 --> May 2025

P1, N=4, Terminated, Pfizer | Trial completion date: Aug 2025 --> Aug 2024 | Active, not recruiting --> Terminated; Strategic business decision

Tau-A and C4G are elevated in serum from patients with recurrent GBM and prognostic for OS. If validated, these biomarkers could be applied to clinical trials.