Zaltrap (ziv-aflibercept IV)

P2, N=32, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Initiation date: Oct 2023 --> Feb 2024

The combination of sapanisertib and ziv-aflibercept was generally tolerable and demonstrated anti-tumor activity in heavily pre-treated patients with advanced malignancies.

P1, N=83, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Jan 2024

P1, N=83, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025

P=N/A, N=140, Completed, Sanofi | Active, not recruiting --> Completed

Although limited by sample size and follow-up, these findings highlight the potential of the combination of ziv-aflibercept antiangiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment and the need for further research to improve outcomes in anti-PD-1-resistant melanoma.

P1, N=78, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=134, Recruiting, Neonc Technologies, Inc. | Not yet recruiting --> Recruiting

P2, N=32, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

P3, N=202, Active, not recruiting, GCS IHFB Cognacq-Jay | Recruiting --> Active, not recruiting | Trial completion date: Aug 2023 --> Jun 2024 | Trial primary completion date: Oct 2022 --> Jun 2023

P1/2, N=134, Not yet recruiting, Neonc Technologies, Inc. | .

P2, N=19, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

P1, N=83, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2023 --> Jan 2024

P2, N=19, Active, not recruiting, Dana-Farber Cancer Institute | N=43 --> 19 | Trial completion date: Dec 2021 --> Dec 2022

The combination of ziv-aflibercept and pembrolizumab demonstrated an acceptable safety profile with antitumor activity in solid tumors. The combination is currently being studied in sarcoma and anti-PD-1-resistant melanoma.

P2, N=117, Completed, Federation Francophone de Cancerologie Digestive | Recruiting --> Completed | Trial primary completion date: Dec 2020 --> Jun 2021

P4, N=124, Ongoing, FONDAZIONE RICERCA TRASLAZIONALE (FORT)

P1, N=83, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | Trial completion date: Dec 2021 --> Jan 2023 | Trial primary completion date: Dec 2021 --> Jun 2021

P2, N=151, Ongoing, FONDAZIONE GISCAD (GRUPPO ITALIANO PER LO STUDIO DEI CARCINOMI DELL'APPARATO DIGERENTE)

P4, N=106, Ongoing, DIP. MEDICINA DEI SISTEMI UNIVERSITà DEGLI STUDI DI ROMA TOR VERGATA

P1, N=69, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021

Chemotherapeutic efficacy did not differ between the groups. Grade 3 or 4 AEs within the first four cycles of treatment and prior BEV exposure may be an effective predictor of treatment efficacy in mCRC patients administered VEGF inhibitors as second-line chemotherapy.

The results show that patients with wt RAS mCRC who received an anti-EGFR as part of the first-line treatment achieved similar RR, PFS, OS, and toxicities to those reported in VELOUR trial. These results suggest that FOLFIRI-aflibercept after first-line treatment with anti-EGFR is an appropriated option for RAS wt mCRC.

We performed a search of all prospective randomized phase III studies in PubMed, ASCO and ESMO congresses for all years before September, 2020, compared chemotherapy (CT) plus bevacizumab or aflibercept or ramucirumab and CT alone at the first-line or second-lines with information of the BRAF status... Addition of anti-angiogenic therapy to chemotherapy showed improvement in the PFS and OS in pts with mBRAF compared with chemotherapy alone. A prospective randomized trial is needed to determine the optimal regimen of systemic therapy for pts with mBRAF mCRC.

The introduction of anti-EGFR (cetuximab and panitumumab) and antiangiogenic (bevacizumab, regorafeninb, ramucirumab, and aflibercept) agents in the therapeutic armamentarium of the metastatic colorectal cancer (CRC) has significantly improved the therapeutic efficacy and patients survival. Host genetic variants in VEGF-dependent (i.e., EGF, IGF-1, HIF1α, eNOS, iNOS) and -independent (i.e., EMT cascade, EGFL7) pathways, with specific attention on inflammation and immune system-related factors (e.g., IL-8, CXCR-1/2, CXCR4-CXCL12 axis, TLRs, GADD34, PPP1R15A, ANXA11, MKNK1), were investigated as predictive markers of bevacizumab outcome, generating some promising results. In this review we aimed to summarize the most recent literature data regarding the potential role of common and rare inhered variants in predicting which CRC patients will benefit more from a specific targeted drug administration.

Although the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.

It is approved for the treatment of metastatic colorectal cancer patients resistant to or progressing after oxaliplatin-containing therapy... Results will be presented at the congress based on the final data analysis and conclusions will be drawn accordingly.

It is approved for the treatment of metastatic colorectal cancer patients resistant to or progressing after oxaliplatin-containing therapy... Results will be presented at the congress based on the final data analysis and conclusions will be drawn accordingly.

It is approved for the treatment of metastatic colorectal cancer patients resistant to or progressing after oxaliplatin-containing therapy... Results will be presented at the congress based on the final data analysis and conclusions will be drawn accordingly.

Regorafenib combined with chemotherapy might be a potential alternative to conventional therapeutic options in second-line treatment of patients with metastatic colorectal cancer and could be considered as the best option for treating patients with KRAS and BRAF mutated mCRC. However future RCTs are needed to confirm these results.

Legal entity responsible for the study: Cecile Torregrosa. Funding: Has not received any funding.

Background Previous trials have demonstrated that bevacizumab and fluoropyrimidine combination is effective and well-tolerated in older patients with metastatic colorectal cancer (mCRC pts). In this randomized phase II trial, we investigated whether the addition of aflibercept to LV5FU2 regimen is effective and well tolerated in mCRC pts not fit for irinotecan/oxaliplatin-based chemotherapy...Funding: Sanofi. Clinical trial identification: EudraCT 2014-001837-10.

P1, N=69, Recruiting, National Cancer Institute (NCI) | Active, not recruiting --> Recruiting

P1, N=69, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

Methods This multicenter, retrospective study aimed to compare clinical outcomes of activity (ORR), efficacy (PFS, combined I and II line PFS [PFS1-PFS2], OS) and safety of WT mCRC patients treated with second-line bevacizumab or aflibercept-based therapy (Bev-CT and Afli-CT, respectively), after a first-line panitumumab or cetuximab-based therapy in a “real-life” setting...Legal entity responsible for the study The author. Funding Has not received any funding.

Anti-angiogenic inhibitors (bevacizumab, ramucirumab, and aflibercept beta (AFL)) showed survival benefit combined with FOLFIRI as second-line chemotherapy in randomized controlled trials...Therefore, we planned a phase II trial of second-line FOLFIRI plus aflibercept in patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibody...FOLFIRI (irinotecan 180mg/m2 , l-leucovorin 200mg/m2 , bolus 5-FU 400mg/m2 and infusional 5-FU 2400mg/m2 /46hrs) and AFL 4mg/kg are administered every 2 weeks until progression or unacceptable toxicities...Legal entity responsible for the study The authors. Funding Sanofi.

Conclusions. Our pooled analysis confirms the efficacy of anti-angiogenics in pre-treated BRAF-mutant CRC, establishing the combination of chemotherapy plus Bevacizumab or Ramucirumab or Aflibercept as a valid treatment option.

Aflibercept beta and FOLFIRI demonstrated acceptable toxicity in heavily pretreated metastatic colorectal cancer patients.

The safety profile of aflibercept is generally manageable and comparable across various geographic locations.

Patients (p) with middle or distal third, mrT3/T4/N2 rectal adenocarcinoma were randomly assigned (2:1), to mFOLFOX6 with (arm 1, n=115) or without Aflibercept (arm 2, n=65) prior to CRT (capecitabine with 50.4 Gy in 28 fractions) and TME... Adding aflibercept to induction mFOLFOX6 is not associated with an improvement in DFS. Our findings suggest that CMSs-IHQ subtypes could be predictive for pCR with this treatment strategy. Research Funding: SANOFI

No abstract available

The lack of validated predictive markers of aflibercept is a weakness for guaranteeing the best treatment management with this drug. This work provides new mechanistic insight of aflibercept depending on Gal-1. Thus, in tumors overexpressing Gal-1 aflibercept has not only an antiangiogenic effect but also prevents Gal-1-mediated tumor-stroma crosstalk. The stronger aflibercept effect in tumors with high levels of Gal-1 points out this protein as a molecular marker to predict the efficacy of this agent not only for NECs but also for other tumors with high levels of this protein.