MedPath

Ramucirumab

Generic Name
Ramucirumab
Brand Names
Cyramza
Drug Type
Biotech
CAS Number
947687-13-0
Unique Ingredient Identifier
D99YVK4L0X
Background

Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells. VEGFR stimulation also mediates downstream signalling required for angiogenesis and is postulated to be heavily involved in cancer progression, making it a highly likely drug target. In contrast to other agents directed against VEGFR-2, ramucirumab binds a specific epitope on the extracellular domain of VEGFR-2, thereby blocking all VEGF ligands from binding to it. Ramucirumab is indicated for us in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy.

Indication

Ramucirumab is indicated for the treatment of advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel for patients who progress after prior fluoropyrimidine- or platinum-containing chemotherapy. It is indicated, in combination with erlotinib, for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor exon 19 deletions or exon 21 (L858R) point mutations. It is also indicated in combination with docetaxel for the treatment of metastatic non-small cell lung cancer in patients who have progressed following prior platinum-based chemotherapy. Patients who have EGFR or ALK genomic aberrations should also have disease progression following FDA-approved therapy for these aberrations. Ramucirumab, in combination with FOLFIRI (folinic acid, fluorouracil, and irinotecan), is indicated for the treatment of metastatic colorectal cancer in patients who have progressed following therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Lastly, ramucirumab is indicated for the treatment of hepatocellular carcinoma in patients with an alpha-fetoprotein level ≥400 ng/mL and have previously been treated with sorafenib.

Associated Conditions
Advanced Gastric or Gastroesophageal Junction Adenocarcinoma, Hepatocellular Carcinoma, Metastatic Colorectal Cancer (CRC), Metastatic Non-Small Cell Lung Cancer, Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Evorpacept-Keytruda Combination Fails to Meet Primary Endpoints in Head and Neck Cancer Trials

• ALX Oncology announced that evorpacept combined with Keytruda (pembrolizumab), with or without chemotherapy, failed to meet primary endpoints in two Phase 2 trials for head and neck squamous cell carcinoma. • Despite showing a manageable safety profile, the company will discontinue pursuing this specific combination for HNSCC treatment, instead focusing on evorpacept's more promising combinations with anti-cancer antibodies in other tumor types. • Evorpacept, a CD47-blocker designed to help the immune system target cancer cells, will continue development in multiple clinical trials for breast cancer, colorectal cancer, non-Hodgkin lymphoma, and multiple myeloma.

SUNLIGHT Trial Highlights Importance of Sequential Therapies in Refractory Colorectal Cancer

• The SUNLIGHT trial demonstrated significant survival benefits when adding bevacizumab to trifluridine/tipiracil in refractory metastatic colorectal cancer, showing a 39% improvement in overall survival. • Despite having three FDA-approved regimens for refractory colorectal cancer (trifluridine/tipiracil plus bevacizumab, fruquintinib, and regorafenib), many patients don't receive all available treatment options. • Dr. John Marshall of Georgetown Lombardi Comprehensive Cancer Center emphasizes the need for personalized sequencing strategies and warns against non-medical factors influencing treatment decisions.

NCCN Awards Three Research Grants to Advance Gastrointestinal Cancer Treatments with Taiho Oncology

• The National Comprehensive Cancer Network has awarded three research grants to investigate tipiracil/trifluridine and futibatinib in gastrointestinal cancers, funded through collaboration with Taiho Oncology, Inc. • Selected research projects will explore novel treatment combinations including TAS-102 with PARP inhibition for pancreatic cancer, futibatinib with paclitaxel/ramucirumab for gastroesophageal cancer, and trifluridine/tipiracil plus oxaliplatin for biliary tract cancer. • The two-year research initiative aims to address significant unmet needs in gastrointestinal cancer treatment, particularly focusing on advanced-stage patients with limited therapeutic options.

FDA Grants Second Fast Track Designation to Innovent's IBI363 for Advanced Squamous NSCLC Treatment

• Innovent's IBI363, a first-in-class PD-1/IL-2α-bias bispecific antibody, received FDA Fast Track Designation for treating advanced squamous non-small cell lung cancer after immunotherapy and chemotherapy failure. • Clinical trials showed promising results with 50% objective response rate in the 3 mg/kg dose group and effectiveness regardless of PD-L1 expression levels, suggesting potential benefits for cold tumors. • The drug demonstrated encouraging disease control rate of 88.9% and favorable safety profile, offering hope for patients with limited treatment options after immunotherapy failure.

Ramucirumab Plus Somatostatin Shows Promise in Advanced Neuroendocrine Tumors with 14.2-Month PFS

A phase 2 trial demonstrated that the combination of ramucirumab (Cyramza) with somatostatin analog therapy achieved a median progression-free survival of 14.2 months in patients with advanced extra-pancreatic neuroendocrine tumors. The treatment showed an encouraging safety profile with manageable adverse events, primarily hypertension, suggesting a potential new therapeutic option for this patient population.

Evorpacept Shows Promise in HER2-Positive Gastric Cancer: Phase 2 ASPEN-06 Trial Results

• The ASPEN-06 Phase 2 trial demonstrated a 41.3% overall response rate (ORR) with evorpacept plus trastuzumab, ramucirumab, and paclitaxel (ETRP) in previously treated HER2-positive gastric cancer patients. • Patients with confirmed HER2-positive tumors via fresh biopsy or ctDNA showed a 48.9% ORR and a median duration of response of 15.7 months with the evorpacept combination. • Evorpacept plus TRP was generally well-tolerated, with adverse events consistent with the control group, suggesting a manageable safety profile in this patient population. • The FDA has granted Fast Track designation to evorpacept for second-line treatment of HER2-positive gastric or gastroesophageal junction carcinoma, highlighting its potential clinical significance.

Evorpacept Shows Promise in HER2-Positive Gastric Cancer: Updated ASPEN-06 Data

• ALX Oncology's ASPEN-06 Phase 2 trial evaluates evorpacept, a CD47-blocker, in HER2-positive advanced gastric cancer patients who have been previously treated. • Updated data from the ASPEN-06 trial were presented at the 2025 ASCO Gastrointestinal Cancers Symposium (ASCO GI). • The virtual event hosted by ALX Oncology on January 23, reviewed the ASPEN-06 data, focusing on evorpacept's potential in immuno-oncology. • The ASPEN-06 trial is a phase 2/3 study of evorpacept in patients with HER2-overexpressing gastric/gastroesophageal cancer.

Sanofi Halts Amcenestrant Development After Disappointing First-Line Breast Cancer Trial

• Sanofi discontinues the development of amcenestrant, an oral selective estrogen receptor degrader (SERD), after it failed in the AMEERA-5 phase 3 trial. • The AMEERA-5 trial compared amcenestrant plus palbociclib to letrozole plus palbociclib as a first-line treatment for HR-positive/HER2-negative advanced breast cancer. • This failure raises concerns about the potential of SERDs in the first-line treatment of breast cancer, impacting other developers in the field. • Sanofi will discontinue all amcenestrant studies, including the AMEERA-6 trial in early-stage HR+ breast cancer patients.

Datroway (Datopotamab Deruxtecan) Receives Global Approvals for Advanced Breast Cancer

• Datroway (Dato-DXd) gains first global approval in Japan for previously treated, unresectable, or recurrent HR-positive, HER2-negative breast cancer, offering a new alternative to conventional chemotherapy. • The FDA has approved Datroway for advanced breast cancer, marking the first U.S. approval for the antibody-drug conjugate developed by AstraZeneca and Daiichi Sankyo. • EMA endorsed Dato-DXd as a late-line option for certain breast cancer cases, adding to approvals in the U.S. and Japan and expanding treatment options in Europe. • Clinical trials, including TROPION-Breast01, demonstrated that Datroway significantly delayed cancer progression compared to standard chemotherapy, with manageable safety profiles.

DATROWAY® (Datopotamab Deruxtecan) Receives EU Approval for Previously Treated Metastatic HR+/HER2- Breast Cancer

• DATROWAY, a TROP2-directed antibody drug conjugate (ADC), has been approved in the European Union for treating adult patients with unresectable or metastatic HR+/HER2- breast cancer who have received endocrine therapy and at least one line of chemotherapy. • The approval is based on the TROPION-Breast01 phase 3 trial, which showed DATROWAY reduced the risk of disease progression or death by 37% compared to chemotherapy, with a median PFS of 6.9 months versus 4.9 months. • This marks the second ADC approved for breast cancer based on Daiichi Sankyo's DXd technology and the third medicine from their oncology pipeline to receive EU approval, highlighting their commitment to developing innovative cancer treatments.

FDA Approves Tevimbra Plus Chemotherapy for First-Line Treatment of Gastric and GEJ Adenocarcinoma

• The FDA has approved Tevimbra (tislelizumab-jsgr) in combination with chemotherapy for first-line treatment of HER2-negative gastric or gastroesophageal junction adenocarcinoma with PD-L1 expression. • The approval was based on the RATIONALE-305 trial, which showed a median overall survival of 15.0 months with Tevimbra plus chemotherapy compared to 12.9 months with chemotherapy alone. • Common side effects of Tevimbra in combination with chemotherapy include decreased blood cell counts, fatigue, and gastrointestinal issues, but the combination offers a manageable safety profile. • This approval marks the second for Tevimbra in 2024, highlighting its potential to address critical needs in oncology and providing a valuable new treatment option.

Cyramza-Tagrisso Combination Extends Progression-Free Survival in EGFR-Mutant NSCLC

• The combination of Cyramza and Tagrisso significantly prolonged progression-free survival (PFS) compared to Tagrisso alone in patients with TKI-naïve EGFR-mutant non-small cell lung cancer (NSCLC). • Median PFS in the combination group was 24.8 months, compared to 15.6 months in the Tagrisso-alone group, demonstrating a clinically meaningful improvement. • The Cyramza-Tagrisso combination showed a manageable safety profile, with no new safety signals identified in the RAMOSE trial. • PFS benefits were observed across major subgroups, including patients with exon 19 deletion, L858R mutation, and those with or without CNS metastases.

FDA Approves Astellas' Vyloy (Zolbetuximab) for Advanced Gastric and GEJ Adenocarcinoma

• The FDA has approved zolbetuximab (Vyloy) in combination with chemotherapy for first-line treatment of CLDN18.2-positive, HER2-negative gastric or GEJ adenocarcinoma. • Approval was based on SPOTLIGHT and GLOW trials, demonstrating statistically significant improvements in progression-free and overall survival compared to chemotherapy alone. • The VENTANA CLDN18 (43-14A) RxDx Assay from Roche was also approved as a companion diagnostic to identify patients eligible for Vyloy treatment. • Vyloy is now approved in five markets worldwide, offering a new targeted therapy option for a subset of gastric and GEJ cancer patients.

Cyramza Plus Lonsurf Fails to Improve Overall Survival in Metastatic Colorectal Cancer

• The phase 3 IKF-AIO-RAMTAS trial showed that adding Cyramza to Lonsurf did not significantly improve overall survival in heavily pretreated metastatic colorectal cancer patients. • Subgroup analysis revealed potential benefits in female patients and those with left-sided tumors, who experienced improved survival outcomes with the Cyramza/Lonsurf combination. • While overall survival was not significantly extended, the combination of Cyramza and Lonsurf did demonstrate a significant improvement in progression-free survival. • The combination therapy showed a manageable safety profile, though with a higher incidence of treatment-related side effects, particularly those associated with Cyramza.

Evorpacept Shows Promise in HER2-Positive Gastric Cancer Treatment

• ALX Oncology's Evorpacept, a CD47 inhibitor, demonstrates favorable results in Phase 2 trials for HER2-positive gastric and gastroesophageal junction (GEJ) cancer. • Evorpacept, combined with trastuzumab, ramucirumab, and paclitaxel (TRP), shows comparable overall response rates to Enhertu in treating HER2-positive gastric cancer. • The Evorpacept plus TRP combination exhibits a longer median duration of response (15.7 months) compared to Enhertu (11.3 months) and TRP alone (7.6 months). • ALX Oncology's stock is currently undervalued, trading below its cash value, presenting a speculative buy opportunity with potential for significant returns if trials succeed.
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