Zaltrap (ziv-aflibercept IV) / Sanofi, Regeneron - LARVOL DELTA

TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "In patients with chemorefractory metastatic colorectal cancer, TAS-102 plus bevacizumab, as compared with TAS-102 monotherapy, was associated with a significant and clinically relevant improvement in progression-free survival with tolerable toxicity. The combination of TAS-102 plus bevacizumab could be a new treatment option for patients with refractory metastatic colorectal cancer and could be a practice-changing development."

Clinical • Journal • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology

Phase I study of sapanisertib (CB-228/TAK-228/MLN0128) in combination with ziv-aflibercept in patients with advanced solid tumors. (PubMed, Cancer Med) - "The combination of sapanisertib and ziv-aflibercept was generally tolerable and demonstrated anti-tumor activity in heavily pre-treated patients with advanced malignancies."

Combination therapy • Journal • Metastases • P1 data • Anorexia • Cardiovascular • Dyslipidemia • Fatigue • Hypertension • Hypertriglyceridemia • Mucositis • Oncology • Sarcoma • Solid Tumor • HIF1A

Efficacy and circulating protein biomarkers of second-line aflibercept plus FOLFIRI according to prior bevacizumab or cetuximab treatment in advanced colorectal cancer (KCSG CO21-21). (ASCO 2026) - P4 | "Clinical outcomes and safety profiles of aflibercept plus FOLFIRI were comparable regardless of prior BEV or CET exposure. Elevated baseline PlGF, IL-8, TIMP-1 and VEGF-A levels were associated with shorter PFS and OS. Exploratory plasma proteomics identified dynamic PIGR expression as a response-associated biomarker linked to inferior OS."

Biomarker • Clinical • Metastases • Colorectal Cancer • Inflammation • Metabolic Disorders • Neutropenia • Oncology • Renal Disease • Solid Tumor • CXCL8 • OLFM1 • S100A8 • TIMP1

Testing the PD-1 Antibody, MK3475, Given With Ziv-aflibercept in Patients With Advanced Cancer (clinicaltrials.gov) - P1 | N=59 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Jan 2027 | Trial primary completion date: Dec 2025 ➔ May 2025

Platinum resistant • Trial completion date • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Genito-urinary Cancer • Melanoma • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor

Handok signs Korea distribution deal for two Sanofi cancer drugs (Chosun Biz) - "HANDOK said on the 22nd that it signed a domestic distribution and sales contract for the French pharmaceutical company Sanofi's anticancer drugs 'Eloxatin (Eloxatin)' and 'Zaltrap (Zaltrap)'....HANDOK plans to exclusively sell the two products in Korea starting in January next year. Eloxatin and Zaltrap are standard treatments for unresectable advanced or metastatic colorectal cancer, gastric cancer, and pancreatic cancer."

Licensing / partnership • Colorectal Cancer • Gastric Cancer • Pancreatic Cancer

Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis (clinicaltrials.gov) - P1/2 | N=134 | Recruiting | Sponsor: Neonc Technologies, Inc. | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Feb 2026 ➔ Feb 2027

IO biomarker • Trial completion date • Trial primary completion date • Astrocytoma • Brain Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • Glioblastoma • Lung Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • PD-L1

Stereotactic Body Radiation Therapy and Aflibercept in Treating Patients With Uveal Melanoma (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University | Completed ➔ Terminated; Slow accrual

Trial termination • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Efficacy and Safety of KH903 Plus FOLFIRI as a Second-Line Treatment in Unresectable Recurrent or Metastatic Colorectal Cancer: A Randomized Phase 2 Study. (PubMed, Clin Colorectal Cancer) - "KH903 in combination with FORFIRI in second-line treatment of patients with mCRC showed prolonged mPFS and mOS, comparing to the similar agents (Avastin®, ZALTRAP®, Cyramza®) and no new safety signals were observed."

Journal • Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor

Assessment of Clinically Meaningful Benefits and Incremental Costs of Adding Bevacizumab to Trifluridine/Tipiracil for Metastatic Colorectal Cancer: A Comparison With Other Combination Regimens (ISPOR-EU 2024) - " Eight regimens—FTD/TPI+BEV, paclitaxel+ramucirumab, fluorouracil+irinotecan+leucovorin (FOLFIRI)+ziv-aflibercept, FOLFIRI+ramucirumab, durvalumab+tremelimumab, durvalumab+ gemcitabine+cisplatin, and nivolumab+chemotherapy (two)—qualified for inclusion after targeted literature review. Combination of BEV and FTD/TPI (vs. FTD/TPI) for the treatment of metastatic colorectal cancer yielded greater clinically meaningful benefits related to OS/PFS, and incremental costs of adding BEV to FTD/TPI were lower than addition of single agents to other regimens for aGIC that are currently used in US clinical practice."

Clinical • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

Testing the PD-1 Antibody, MK3475, Given With Ziv-aflibercept in Patients With Advanced Cancer (clinicaltrials.gov) - P1 | N=78 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Genito-urinary Cancer • Melanoma • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CD4 • CD8 • CTAG1B • FGF • HGF • MLANA

Budgetary impact of adding ziv-aflibercept to a United States health plan formulary as a post-oxaliplatin biologic option for patients with metastatic colorectal cancer (mCRC) (ASCO-GI 2015) - Abstract #765; "Using April 2013 utilization rates (including ziv-aflibercept at 3.4%), estimated treatment costs were $5.259M, a per-member-per-month (PMPM) cost of $0.0438....The model suggests cost savings primarily due to lower unit costs for ziv-aflibercept and lower death-related costs, rather than decreased adverse event management."

HEOR • Colorectal Cancer • Oncology

Potential predictive and prognostic biomarkers identified in baseline plasma samples from the VELOUR trial (ASCO-GI 2015) - Abstract #638; P3, N=533; VELOUR; "For OS, the hazard ratio (HR) was 0.809 in the plasma biomarker population vs. HR =0.817 in the overall VELOUR population. For PFS, the HR = 0.752 in the plasma biomarker population vs. HR = 0.758 in VELOUR....No biomarker subset corresponded to worse OS with ziv-aflibercept treatment."

Biomarker • Colorectal Cancer • Oncology

Cancer Metastases to the Liver: Mechanisms of Tumor Cell Colonization. (PubMed, Pharmaceuticals (Basel)) - "We examine randomized studies focusing on median survival duration and median overall survival in patients administered placebo compared with those treated with bevacizumab, ramucirumab, regorafenib, and ziv-aflibercept in addition to current chemotherapy. Finally, we discuss the significance of non-pharmacological methods, including surgical procedures, radiotherapy, cryotherapy, radiofrequency ablation (RFA), and transarterial embolization (TAE). In conclusion, the given methods can successfully prevent metastases to the liver and prolong the median survival duration and median overall survival in patients suffering from cancer."

Journal • Review • Tumor cell • Colorectal Cancer • Oncology • Solid Tumor

Resection of colorectal liver metastases with second-line aflibercept plus FOLFIRI: Results from the RESECTION prospective French cohort (Eur J Cancer) - P=Obs | N=140 | NCT05178745 | Sponsor: Sanofi | "A total of 137 patients (median age 65 years, RAS/BRAF mutant 57%/9%) were enrolled at 22 French sites. CLM (median 4) were synchronous in 82%, bilobar in 71% and located in liver only in 54%. Overall, 17% of patients had R0/R1 resection (21% for patients with liver-only disease). A major pathological response per Blazer score was observed in 55% of resected patients, along with significantly longer OS (median 34.8 vs 9.1 months, p<0.0001) and PFS (median 11.4 vs 4.9 months, p<0.0001) compared to non-resected patients."

Observational data • Colorectal Cancer

Prospective, Observational Study of Aflibercept Use in Combination with FOLFIRI in Patients with Metastatic Colorectal Cancer: A Real-World Effectiveness Study (Multidisciplinary Digital Publishing Institute) - P=Obs | N=93 | "A total of 93 patients were treated at 17 Polish sites. A median of 10 cycles was administered. Over a median treatment duration of 5.3 months, median PFS and median OS were 8.4 months [95% CI, 6.9–9.9] and 27.0 months [95% CI, 23.9–30.1], respectively. There was no significant impact of primary tumor location, metastatic site, or KRAS status on PFS and OS."

Observational data • Colorectal Cancer

Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Initiation date: Oct 2023 ➔ Feb 2024

Metastases • Trial initiation date • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

First-Line LV5FU2 with or without Aflibercept in Patients with Non-Resectable Metastatic Colorectal Cancer: A Randomized Phase II Trial (PRODIGE 25-FFCD-FOLFA) (Multidisciplinary Digital Publishing Institute) - P2 | N=117 | FOLFA (NCT02384759) | "A total of 117 patients, with a median age of 81 years, were included: 59 in arm A (LV5FU2-aflibercept) and 58 in arm B (LV5FU2 alone). Six-month PFS was 54.7% in both arms (90% CI 42.5–66.5 in both). Median overall survival was 21.8 months (arm A) and 25.1 months (arm B). Overall toxicity was more common in arm A: grade ≥ 3 toxicity in 82% versus 58.2%."

P2 data • Colorectal Cancer

Sapanisertib and Ziv-Aflibercept in Treating Patients With Recurrent Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=83 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: Jan 2025 ➔ Jan 2024

Combination therapy • Metastases • Surgery • Trial completion • Trial completion date • Endocrine Cancer • Hepatocellular Cancer • Hepatology • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

Sapanisertib and Ziv-Aflibercept in Treating Patients With Recurrent Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=83 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jan 2024 ➔ Jan 2025

Combination therapy • Metastases • Surgery • Trial completion date • Endocrine Cancer • Hepatocellular Cancer • Hepatology • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

A Prospective Observational Cohort Study Evaluating Resection Rate in Patients With Metastatic Colorectal Cancer Treated With Aflibercept in Combination With FOLFIRI - Observatoire résection (clinicaltrials.gov) - P=N/A | N=140 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Ziv-aflibercept plus pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment. (PubMed, Cancer Immunol Immunother) - P1 | "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."

Journal • Metastases • Eye Cancer • Melanoma • Mucosal Melanoma • Ocular Melanoma • Oncology • Solid Tumor • CXCL10 • PD-L1

Testing the PD-1 Antibody, MK3475, Given With Ziv-aflibercept in Patients With Advanced Cancer (clinicaltrials.gov) - P1 | N=78 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Genito-urinary Cancer • Melanoma • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • CD4 • CD8 • CTAG1B • FGF • HGF • MLANA

Safety and Efficacy of NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Brain Metastasis (clinicaltrials.gov) - P1/2 | N=134 | Recruiting | Sponsor: Neonc Technologies, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Astrocytoma • Brain Cancer • CNS Tumor • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Melanoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • PD-L1

FDA-Approved Drugs: Biologic License Application (BLA): 125418 (FDA) - Supplement submission for Zaltrap approved on 13th December 2023

sBLA • Colorectal Cancer

Real-world Data of Aflibercept (AFL)- Based Treatment (Tx) in Metastatic Colorectal Cancer (MCRC) Patients (PTS): Data from the Italian Medicines Agency (AIFA) Monitoring Registry (AIOM 2023) - P=NA | N=5837 | "Italian real-world data are in line with the evidence available from the VELOUR trial of afl-based tx in mCRC pts. The association between increased afl reduction/interruption events and baseline hypertension is of interest. This is the first analysis showing both a lower probability of afl reduction/interruption and a reduced TTE in patients previously treated with BV."

Clinical data