Evorpacept Combo for Stomach Cancer
Recruiting in Palo Alto (17 mi)
+84 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: ALX Oncology Inc.
Must not be taking: Steroids, Anti-CD47, Anti-SIRPα
Disqualifiers: CNS metastases, Leptomeningeal disease, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?A Phase 2/3 Study of Evorpacept (ALX148) in Combination With Trastuzumab, Ramucirumab, and Paclitaxel in Patients With Advanced HER2-overexpressing gastric/GEJ adenocarcinoma.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you have been treated with ramucirumab or any anti-CD47 or anti-SIRPα agent before, you cannot participate.
What data supports the idea that Evorpacept Combo for Stomach Cancer is an effective treatment?
The available research does not provide specific data on the effectiveness of Evorpacept Combo for Stomach Cancer. However, it highlights that other treatments like trastuzumab combined with chemotherapy have shown improved outcomes for HER2-positive gastric cancer. Additionally, pembrolizumab combined with trastuzumab and chemotherapy has shown promise in improving response rates. These findings suggest that combining targeted therapies with chemotherapy can be beneficial for treating advanced gastric cancer.
12345What safety data is available for Evorpacept Combo for Stomach Cancer?
The provided research does not contain specific safety data for Evorpacept Combo for Stomach Cancer. It primarily discusses the use of H2 antagonists in paclitaxel premedication regimens and the prevention of chemotherapy-induced nausea and vomiting. For safety data on Evorpacept or its combinations, further specific studies or clinical trial results would be needed.
678910Is the drug Evorpacept Combo a promising treatment for stomach cancer?
Yes, the drug Evorpacept Combo is promising for stomach cancer because it combines several effective treatments. Trastuzumab is known to help people with a specific type of stomach cancer, and ramucirumab with paclitaxel has shown to improve survival. This combination could potentially offer significant benefits for patients.
511121314Eligibility Criteria
This trial is for adults with advanced HER2+ gastric or gastroesophageal junction cancer that's worsened after treatment with a HER2-targeted therapy and chemo. Participants must have good organ function and physical health. Those with brain metastases needing steroids, previous anti-CD47/SIRPα therapy, or ramucirumab treatment can't join.Inclusion Criteria
My advanced stomach cancer worsened after treatment with HER2 and chemotherapy.
My bone marrow is working well.
I am physically active and can do most of my daily activities.
+1 more
Exclusion Criteria
I have never been treated with anti-CD47 or anti-SIRPα drugs.
I need steroids for my brain or spinal cord cancer symptoms.
I have been treated with ramucirumab before.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment Phase 2
Participants receive Evorpacept (ALX148) in combination with Trastuzumab, Ramucirumab, and Paclitaxel in a 28-day cycle
16 weeks
4 visits (in-person) per cycle
Treatment Phase 3
Participants receive Evorpacept (ALX148) or comparator treatments in a 28-day cycle
Up to 36 months
4 visits (in-person) per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests Evorpacept (ALX148) combined with Trastuzumab, Ramucirumab, and Paclitaxel in patients whose stomach cancer has high levels of the HER2 protein. It aims to see if this combo helps more than current treatments.
4Treatment groups
Experimental Treatment
Active Control
Group I: Phase 3 - Arm AExperimental Treatment4 Interventions
Evorpacept (ALX148) 30 mg/kg Q2W IV, trastuzumab (initial dose of 6 mg/kg followed by 4 mg/kg) Q2W IV, ramucirumab 8 mg/kg Q2W IV, and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle.
Group II: Phase 2 - Arm AExperimental Treatment4 Interventions
Evorpacept (ALX148) 30 mg/kg Q2W IV, trastuzumab (initial dose of 6 mg/kg followed by 4 mg/kg) Q2W IV, ramucirumab 8 mg/kg Q2W IV, and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle.
Group III: Phase 2 - Arm BActive Control3 Interventions
Trastuzumab (initial dose of 6 mg/kg followed by 4 mg/kg) Q2W IV, ramucirumab 8 mg/kg Q2W IV, and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle.
Group IV: Phase 3 - Arm BActive Control2 Interventions
Ramucirumab 8 mg/kg Q2W IV and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutchinson Cancer CenterSeattle, WA
The Oncology Institute of Hope & InnovationAnaheim, CA
Vanderbilt University Medical CenterNashville, TN
NEXT VirginiaFairfax, VA
More Trial Locations
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Who Is Running the Clinical Trial?
ALX Oncology Inc.Lead Sponsor
Eli Lilly and CompanyIndustry Sponsor
References
Successful treatment of a patient with HER2-positive metastatic gastric cancer with third-line combination therapy with irinotecan, 5-fluorouracil, leucovorin and trastuzumab (FOLFIRI-T). [2015]For patients with HER2-overexpressing gastric cancer, there is an improved prognosis with additional trastuzumab to chemotherapy with a platinum compound and a fluoropyrimidin in first-line therapy. Second-line combinations are currently evaluated in various studies.
Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]Biologic agents, including targeted antibodies as well as immunomodulators, are demonstrating unparalleled development and study across the entire spectrum of human malignancy. This review summarizes the current state of biologic therapies for esophageal, esophagogastric, and gastric malignancies, including those that target human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), c-Met, mechanistic target of rapamycin (mTOR) and immunomodulators. We focus primarily on agents that have been included in phase II and III clinical trials in locally advanced, progressive, or metastatic esophageal and gastric malignancies. At this time, only two biologic therapies are recommended by the National Comprehensive Cancer Network (NCCN): trastuzumab for patients with esophageal/esophagogastric or gastric adenocarcinomas with HER2 overexpression and ramucirumab, a VEGFR-2 inhibitor, as a second-line therapy for metastatic disease. However, recent reports of increases in overall and progression-free survival for agents including pertuzumab, apatinib, and pembrolizumab will likely increase the use of targeted biologic therapy in clinical practice for esophageal and gastric malignancies.
[Advances in Treatment of Human Epidermal Growth Factor Receptor 2-Positve Gastric Cancer]. [2022]Gastric cancer ranks as the fifth most common malignant tumor worldwide and the fourth leading cause of cancer-related deaths.Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer is a special type of gastric adenocarcinoma,the prognosis of which can be improved by trastuzumab plus cytotoxic chemotherapy such as cisplatin and fluorouracil.Pembrolizumab on the basis of Tmabplus chemotherapy can further improve the overall response rate,which has become the first-line standardized therapy against HER2-positive gastric cancer.However,there are still some obstacles such as the innate resistance to Tmab in specific populations.The research on HER2-targeted therapy provides clues for clinical decision-making.This review documents the current neoadjuvant and adjuvant therapies against late-stage HER2-positive gastric cancer,as well as the progress in novel HER2 pathway-targeted drugs.
First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. [2021]Treatment options for patients with HER2-positive advanced gastric cancer are limited, and the prognosis for these patients is poor. Pembrolizumab has demonstrated promising antitumor activity in patients with advanced gastric or gastroesophageal junction adenocarcinoma as monotherapy, in combination with chemotherapy and in combination with trastuzumab. Combining pembrolizumab with trastuzumab and chemotherapy may therefore provide a benefit for patients with advanced HER2-positive gastric cancer. Here we aimed to describe the design of and rationale for the randomized, double-blind, placebo-controlled Phase III KEYNOTE-811 study, which will evaluate the efficacy and safety of pembrolizumab or placebo in combination with trastuzumab and chemotherapy as first-line treatment for patients with advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma. Clinical trial registration: NCT03615326 (ClinicalTrials.gov).
Chemotherapy for advanced gastric cancer. [2023]Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen.
Histamine-2 (H2 ) antagonists can be safely removed from standard paclitaxel premedication regimens. [2022]Label="AIMS">The aim of this study is to investigate the rates of hypersensitivity reactions (HSRs) in patients receiving paclitaxel chemotherapy, with and without a histamine-2 (H2 ) antagonists.
One shot NEPA plus dexamethasone to prevent multiple-day chemotherapy in sarcoma patients. [2021]Label="PURPOSE" NlmCategory="OBJECTIVE">Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared and disturbing adverse events of cancer treatment associated with decreased adherence to effective chemotherapy regimens. For high-risk soft tissue sarcoma patients, receiving multiple-day chemotherapy (MD-CT), antiemetic guidelines recommend a combination of an NK1 receptor antagonist (NK1-RA), a 5-HT3 receptor antagonist (5HT3-RA), and dexamethasone on each day of the antineoplastic treatment. NEPA is the first oral fixed-dose combination of a highly selective NK1-RA, netupitant, and second-generation 5HT3-RA, palonosetron. So far, no data has been published in literature about the efficacy of a single dose of NEPA in MD-CT.
The added value of H2 antagonists in premedication regimens during paclitaxel treatment. [2023]Ranitidine, a histamine 2 blocker, is the standard of care to prevent hypersensitivity reactions (HSRs) caused by paclitaxel infusion. However, the added value of ranitidine in this premedication regimen is controversial. Therefore, we compared the incidence of HSRs during paclitaxel treatment between a standard regimen including ranitidine and a regimen without ranitidine.
Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy. [2013]The purpose of this phase III trial was to evaluate the efficacy and safety of regimens containing casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting during the first cycle in patients receiving moderately emetogenic chemotherapy (MEC).
No need for H2-antagonists in premedication regimens for paclitaxel infusions: less is more. [2021]The theoretical basis for use of histamine 2 (H2)-receptor inhibitors to prevent hypersensitivity reactions for paclitaxel infusions is weak. This Editorial discusses a clinical study showing that ranitidine is not indicated any more in this setting and puts this in the context of other valuable efforts leaving non-evidence-based interventions behind us.
Perspectives in chemotherapy of advanced gastric cancer. [2019]A review of recent phase II and III studies in advanced gastric carcinoma is presented. Several combination regimens have been developed with high activity in locally advanced and metastatic disease. Among them are etoposide plus adriamycin plus cisplatin (EAP), etoposide plus 5-fluorouracil plus leucovorin (ELF), continuous infusion 5-fluorouracil plus cisplatin and high dose methotrexate plus 5-fluorouracil plus adriamycin (FAMTX). In locally advanced disease a resectability rate of +/- 50% has been reported with these protocols. So far only FAMTX has demonstrated superiority compared with 5-fluorouracil, adriamycin and mitomycin (FAM), which regimen has been considered 'standard' treatment for many years. Randomized studies in which the other regimens are being more definitely assessed are underway.
Phase II study of sequential high-dose methotrexate (MTX) and 5-fluorouracil (F) alternated with epirubicin (E) and cisplatin (P) [FEMTX-P] in advanced gastric cancer. [2020]FAMTX (5-fluorouracil, adriamycin, methotrexate) is one of the most effective drug combinations in gastric cancer. Therefore, modifications of FAMTX appear of interest and the FEMTX-P regiment was conceived.
Chemotherapy for advanced gastric cancer: review and update of current practices. [2023]No standard adjuvant or palliative chemotherapy regimen has been internationally approved for patients with advanced gastric cancer. Adjuvant chemoradiotherapy is administered prior to surgery and is used in the Unitied States, and intensified chemotherapy is administered prior to and after surgery and is used in Europe. Limited D1 dissections are also frequently performed in the United States and Europe. In Korea, patients undergoing D2 resection appear to benefit from postoperative adjuvant chemotherapy using S-1 or capecitabine plus oxaliplatin. Fluoropyrimidine, platinum, taxane, epirubicin, and irinotecan may be employed alone or in combination as a first-line therapy in a palliative chemotherapy regimen. In Asia, an orally administered fluoropyrimidine, such as capecitabine or S-1, is favored over the continuous infusion of 5-fluorouracil because of its convenience. Trastuzumab has been integrated into the current standard chemotherapy for human epidermal growth factor receptor 2-overexpressing gastric cancers. There is currently no standard regimen for secondary palliative chemotherapy. Clinical studies of several targeted therapies are ongoing.
FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer. [2017]The chemotherapy regimens of high-dose methotrexate, high-dose fluorouracil (FU), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and leucovorin (FAMTX) and etoposide, Adriamycin, and cisplatin (EAP) have both been reported in nonrandom assignment trials to have high overall response rates and substantial complete response rates in patients with gastric cancer, as well as major toxicities of myelosuppression. Here we report a prospective, stratified, random-assignment comparison of the two combinations in previously untreated patients with advanced gastric cancer.