Cyramza (ramucirumab)

Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC.

He was given oxaliplatin plus S-1 therapy...The patient underwent adjuvant chemotherapy with docetaxel plus S-1...He underwent second-line therapy with paclitaxel and ramucirumab...He was switched to third-line therapy with nivolumab. He is currently arrive 12 months after surgery.

Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1). This trial has been registered at the ClinicalTrials.gov: NCT06169410 (registration date: December 5, 2023).

P1, N=215, Active, not recruiting, Eli Lilly and Company | Trial completion date: Mar 2024 --> Jul 2024

P2, N=168, Recruiting, Canadian Cancer Trials Group | Not yet recruiting --> Recruiting

P1, N=30, Recruiting, Tianjin Medical University Cancer Institute and Hospital | Phase classification: P2 --> P1 | Initiation date: Jun 2023 --> Jun 2024

P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Sep 2024 | Trial primary completion date: Jun 2024 --> Sep 2024

P2/3, N=224, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Mar 2024 --> Jun 2024

P2, N=23, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Mar 2024 --> Jul 2024

P1/2, N=47, Terminated, Basilea Pharmaceutica | Phase classification: P1b/2 --> P1/2

P3, N=589, Recruiting, AstraZeneca

There are three currently active sub-studies and one soon to be activated sub-study studying amivantamab-vmjw in MET amplification positive NSCLC (S1900J). Current sub-studies: S1900E (KRAS) activated on April 2, 2021 and is studying sotorasib (AMG 510) in non-squamous NSCLC...S1900G (EGFR and MET) activated on April 3, 2023 and is studying capmatinib and osimertinib with or without ramucirumab in NSCLC. S1900K (MET exon 14 skipping) activated on December 18, 2023 and is studying tepotinib with or without ramucirumab in NSCLC...One hundred seventy (7%) were submitted with the classification of "Other". The most common reasons included: no sub studies available, patient chose hospice, and patient transferred to different hospital.

In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR-TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large-scale registry-based cohort studies may be needed to validate our findings.

P1, N=174, Active, not recruiting, ALX Oncology Inc. | Trial completion date: Feb 2024 --> Dec 2024

Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

P3, N=545, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2023 --> Dec 2024

In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/- ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/- ramucirumab in this patient population.

Progression-free survival in the CA125-increased group, defined by an increase of 0.0067%/day using receiver operating characteristic curve analysis, was significantly poorer among patients with peritoneal metastases. In conclusion, this study highlights that CA125 kinetics can serve as an early predictor for the progression of peritoneal metastasis during TAX/RAM treatment.

P=N/A, N=257, Recruiting, Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company | N=368 --> 257

P=N/A, N=368, Recruiting, Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company | Not yet recruiting --> Recruiting

Medical records of patients with aGEC enrolled in the randomized phase II AIO-STO-0417 trial after treatment failure to first-line FOLFOX plus nivolumab and ipilimumab were retrospectively analyzed...Patients with CPS ≥1 in the RAM group showed better tumor control (ORR 25% vs 10%) and improved survival (total OS 11.5 vs 8.0 months; second-line OS 6.5 vs 3.9 months; PFS 4.5 vs 1.6 months) compared to the control. Prior exposure to first-line FOLFOX plus dual checkpoint inhibition followed by RAM plus chemotherapy shows favorable response and survival rates especially in patients with initial response and positive PD-L1 expression and has the potential to advance the treatment paradigm in aGEC.

P2, N=7, Active, not recruiting, Imugene Limited | Recruiting --> Active, not recruiting | N=30 --> 7

No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression.

Among them, trastuzumab, as the first targeted drug for gastric cancer, effectively inhibits the proliferation and metastasis of tumor cells by targeting overexpressed HER2, and has become the standard treatment for HER2-positive gastric cancer patients. Ramucirumab, on the other hand, inhibits tumor angiogenesis by targeting VEGFR2 and has been used as second-line therapy for advanced gastric cancer patients. In addition, bemarituzumab targets overexpressed FGFR2, while zolbetuximab targets overexpressed CLDN18.2, significantly extending progression-free survival and overall survival in patients with gastric cancer in clinical trials. This article reviews the roles of tumor driver genes in the progression of gastric cancer; and the treatment strategies for gastric cancer based on targeting HER2, VEGF, FGFR2, CLDN18.2, MET and other tumor driver genes, aiming to provide reference for clinical application of targeted therapy for gastric cancer.

The survival benefit seems to be mainly from PD-L1 positive patients. Subsequent immunotherapy with Atezolizumab did not increase irAE rate.

Furthermore, a drug that targets the vascular endothelial growth factor receptor 2 (VEGFR2, ramucirumab) was deployed, which effectively inhibited angiogenesis and impeded tumor invasion. This innovative preclinical model was used for investigating distinct responses for various drug combinations, encompassing HER2 inhibitors and angiogenesis inhibitors, within the context of PDTS. This integrated platform could potentially advance precision medicine by harmonizing diverse data points within the tumor microenvironment with a focus on the interplay between cancer and the vascular system.

P1, N=715, Recruiting, Taiho Pharmaceutical Co., Ltd. | N=367 --> 715 | Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026

P2/3, N=224, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Jun 2024 --> Mar 2024

P2, N=38, Recruiting, Memorial Sloan Kettering Cancer Center

In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.

These in vitro findings suggest that compared with ramucirumab-plus-paclitaxel, tepotinib-plus-paclitaxel better inhibits the growth of c-MET-positive GC cells, cells lacking MET amplification but containing phosphorylated MET, and cells containing MET mutations. Clinical studies are required to confirm the therapeutic effects of these regimens.

A systematic search of clinical trials found that combining erlotinib (a first-generation TKI) with bevacizumab or ramucirumab (angiogenesis inhibitors) improved progression-free survival (PFS) in EGFRm advanced NSCLC patients compared to TKI alone. The combination treatment was associated with a higher incidence of severe adverse events. Overall, combining erlotinib or another TKI with an angiogenesis inhibitor is a safe and effective alternative for first-line treatment in EGFRm advanced NSCLC, particularly in countries without access to osimertinib and for patients with the EGFR L858R mutation.

Clinical strategy changes, including gastrectomy, HER2 testing, and approval of new drugs, may be associated with improved OS in patients with AGC. In the last 4 years, a remarkable improvement has been observed in patients with LM.

The pretreatment plasma sVEGFR-1 and sVEGFR-3 levels could be predictive biomarkers for distinguishing BEV and RAM when combined with chemotherapy in 2L mCRC treatment. Based on the VEGF-A dynamics at progression, selecting RAM or AFL for patients with significantly elevated VEGF-A levels may be a 2L treatment strategy, with BEV considered for the third-line treatment.

P2, N=31, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

The patient received postoperative chemotherapy with S-1 and oxaliplatin...After the operation, 41 courses of ramucirumab with nab-paclitaxel were administered as a second-line treatment, and she received systemic drug treatment. Sixty months after the gastrectomy, the patient developed left hydronephrosis due to peritoneal metastases and was treated with nivolumab after ureteral stent replacement...Comprehensive multidisciplinary treatment, including surgical and local therapy for peritoneal dissemination based on drug therapy for unresectable advanced gastric cancer, may result in long-term survival. Further research and accumulation of such cases would lead to the development of novel treatments.

The patient underwent sigmoidectomy with D3 lymph node dissection and partial bladder resection for sigmoid colon cancer(cT4bN1M0, cStage Ⅲa), after preoperative chemotherapy with mFOLFOX plus panitumumab, and FOLFOXIRI plus bevacizumab...Although he was treated with FOLFIRI plus ramucirumab or aflibercept, resulted in progression of disease, then he received trifluridine tipiracil hydrochloride plus bevacizumab...He has received pembrolizumab for 4 years without another recurrence. Here, we report a case of MSI-high sigmoid colon cancer in which long-term survival was achieved by pembrolizumab for recurrent lesions resistant to conventional chemotherapy.

Capecitabine and oxaliplatin was started as an adjuvant therapy, and capecitabine was administered until 1 year postoperatively...After 5 courses of paclitaxel and ramucirumab, nivolumab was started as a fourth-line therapy for the recurrence of the right supraclavicular lymph nodes, bone, and liver. She had some immune-related adverse events(irAE), including hypothyroidism and hypoadrenocorticism, which required management, but she maintained PR more than 2 years after the initiation of the treatment. Multimodality therapies, including repeated resection and nivolumab, were considered to help her long-term survival.

Treatment-emergent post-progression EGFR T790M rates were higher in the common versus uncommon and E746del versus L747 deletion subgroups. RAM plus ERL provides benefit and improves treatment outcomes for patients with metastatic NSCLC with EGFR ex19del variants.

The present retrospective study aimed to review patients with metastatic gastric cancer who were treated with paclitaxel (PTX) and RAM followed by nivolumab. However, no significant relationship was observed between the outcome of first-line treatment and nivolumab. The therapeutic effect of nivolumab was associated with prior PTX + RAM treatment in advanced gastric cancer.

P1, N=187, Recruiting, Toray Industries, Inc | Trial completion date: Aug 2024 --> Mar 2025 | Trial primary completion date: Aug 2024 --> Mar 2025

Although the regimen was changed to ramucirumab plus paclitaxel chemotherapy, the patient died 8 months after the initiation of chemotherapy. An accumulation of cases is needed to establish treatment strategies for gastric cancer with PCL and/or DCBM.