Merck’s cancer star Keytruda could be on its way to an updated label in HER2-positive stomach cancer after showing it can stave off tumor progression in a combination study.
Gastric cancer ranks as the fourth leading cause of cancer-related deaths worldwide and the third in China. The overall five-year survival rate stands at approximately 20%. Radical gastrectomy has emerged as a prominent approach in the comprehensive treatment of gastric cancer, aiming to achieve a cure. Over time, advancements in clinical research have led to the evolution of gastric cancer surgery, transitioning from open surgery to laparoscopic surgery and subsequently to robotic surgery.
Summary
- Patients with upper GI cancers are in dire need of new therapeutic options.
- Astellas is sitting on a shoo-in approval for a brand new targeted therapy based on highly promising clinical trial data.
- An approval in this space could mean important new revenue inroads for the company.
CLAUDIN-18 Splice Variant 2
(claudin-18.2; CLDN18.2) has become a promising target for the treatment of patients with digestive malignancies, such as gastric cancer (GC), gastroesophageal junction (GEJ) cancer, esophageal cancer, and pancreatic cancer, because of its limited expression in healthy tissues and abnormal overexpression in a range of malignancies.1 Multiple clinical trials of CLDN18.2-targeted therapies, including monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapies, are ongoing, with some showing promising early results.1 If these findings hold up in larger trials, standardizing methods of CLDN18.2 detection and positivity thresholds, optimizing novel therapies’ efficacy and safety profiles, and finding rational therapeutic combinations with existing agents will be help to integrate CLDN18.2-targeted therapies into clinical practice.1
The FDA has granted orphan drug designation to ATG-022, a Claudin 18.2 (CLDN18.2) antibody-drug conjugate (ADC), for the treatment of patients with gastric cancer and pancreatic cancer, according to a press release from developer Antengene Corporation Limited.1
Treatment with avelumab (Bavencio) plus GEN-001 in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma has demonstrated positive antitumor activity, according to an announcement by Genome & Company.1
The finding comes from a phase 2 study (NCT05419362) of GEN-001 in combination with avelumab, for which the primary end point is objective response rate (ORR), and the secondary end points are the incidence of adverse events (AEs), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). An exploratory end point in the study is analyzing microbiota.
A treatment currently under review by the Food and Drug Administration (FDA) for the treatment of patients with advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma has been shown to improve patients’ overall survival, according to an announcement from the biotechnology company behind the treatment.
Interim results of the RATIONALE 305 study showed that tislelizumab in combination with chemotherapy resulted in a median overall survival time (from the start of the trial until death of any cause) of 17.2 months, compared to 12.6 months for patients who received chemotherapy and a placebo, according to an announcement from drug’s manufacturer, BeiGene.
Full Title
A Phase 2 Trial to Evaluate the Safety and Efficacy of Combination Therapies in Patients with Advanced Upper Gastrointestinal Tract Malignancies (EDGE-Gastric)
Purpose
The purpose of this study is to assess the safety and effectiveness of the investigational drugs domvanalimab and zimberelimab given together with or without FOLFOX chemotherapy in people with inoperable or metastatic upper digestive cancers. Both domvanalimab and zimberelimab take the brakes off the immune response by blocking certain proteins, enabling the immune system to find and destroy cancer cells. FOLFOX is a combination of chemotherapy drugs which is commonly used to treat digestive cancers.
Participants in this study who have not received any prior treatment for their cancer will receive domvanalimab, zimberelimab, and FOLFOX. Those who did receive previous therapy will receive domvanalimab and zimberelimab without FOLFOX. The medications used in this study are given intravenously (by vein).
Eligibility
To be eligible for this study, patients must meet several requirements, including:
- Participants must have inoperable or metastatic cancer of the esophagus, stomach, or junction between the esophagus and stomach.
- Any prior anticancer treatment must have been completed 4 or more weeks before receiving the study therapy.
- Patients must be physically well enough that they are able to be mobile, take care of themselves, and engage in all but physically strenuous activities. For example, they must be well enough that they could carry out office work or light housework.
- This study is for people age 18 and older.
Contact
For more information and to ask about eligibility for this study, please contact the office of Dr. Yelena Janjigian at 646-888-4186.
Protocol
Phase
Investigator
Co-Investigators
Abstract: The tumour microenvironment (TME) is vital to tumour development and influences the immunotherapy response. Abnormal nucleotide metabolism (NM) not only promotes tumour cell proliferation but also inhibits immune responses in the TME. Therefore, this study aimed to determine whether the combined signatures of NM and the TME could better predict the prognosis and treatment response in gastric cancer (GC). 97 NM-related genes and 22 TME cells were evaluated in TCGA-STAD samples, and predictive NM and TME characteristics were determined. Subsequent correlation analysis and single-cell data analysis illustrated a link between NM scores and TME cells. Thereafter, NM and TME characteristics were combined to construct an NM-TME classifier. Patients in the NMlow/TMEhigh group exhibited better clinical outcomes and treatment responses, which could be attributed to the differences in immune cell infiltration, immune checkpoint genes, tumour somatic mutations, immunophenoscore, immunotherapy response rate and proteomap. Additionally, the NMhigh/TMElow group benefited more from Imatinib, Midostaurin and Linsitinib, while patients in the NMlow/TMEhigh group benefited more from Paclitaxel, Methotrexate and Camptothecin. Finally, a highly reliable nomogram was developed. In conclusion, the NM-TME classifier demonstrated a pretreatment predictive value for prognosis and therapeutic responses, which may offer novel strategies for strategizing patients with optimal therapies.