Evorpacept Combo for Stomach Cancer

Not currently recruiting at 107 trial locations

Overseen By Sophia Randolph, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: ALX Oncology Inc.

Must not be taking: Steroids, Anti-CD47, Anti-SIRPα

Disqualifiers: CNS metastases, Leptomeningeal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced stomach cancer that overexpresses the HER2 protein. The researchers aim to determine if adding Evorpacept (a CD47/SIRPa-blocking agent) to standard treatments like trastuzumab, ramucirumab, and paclitaxel can better control the disease. The trial includes different groups, with some receiving the new combination and others continuing with the usual treatments. This trial may suit individuals whose HER2-positive stomach cancer has worsened after initial treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to potentially benefit from an innovative approach.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that evorpacept, when combined with treatments like trastuzumab, ramucirumab, and paclitaxel, can benefit patients with advanced stomach cancer. One study found that this combination led to better response rates compared to other treatments. However, safety remains a critical concern.

Safety data has shown mixed results. In one study, two patients died from treatment-related complications, including a severe immune response and an overreaction of the immune system. Although these serious side effects are rare, they are important to consider.

The treatment is in Phase 2/3 trials, indicating it has been tested in people but is still under study for safety and effectiveness. This phase suggests that researchers have some confidence in the treatment's safety but continue to monitor for any issues. Overall, while the treatment shows promise, its safety requires careful consideration based on these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Evorpacept (ALX148) because it offers a unique approach to treating stomach cancer. Unlike other treatments that typically target the tumor directly, Evorpacept works by blocking a protein called CD47, which cancer cells use to evade the immune system. By inhibiting CD47, Evorpacept empowers the body's own immune defenses to recognize and attack cancer cells more effectively. This novel mechanism of action sets it apart from traditional chemotherapy drugs like paclitaxel and targeted therapies such as trastuzumab and ramucirumab, potentially enhancing treatment effectiveness and outcomes for patients with stomach cancer.

What evidence suggests that this trial's treatments could be effective for advanced HER2-overexpressing gastric/GEJ adenocarcinoma?

Research has shown that evorpacept, combined with trastuzumab, ramucirumab, and paclitaxel, holds promise for treating advanced gastric cancer with high HER2 levels. In this trial, participants in Phase 3 - Arm A will receive this combination treatment. One study showed a 52% overall response rate with this combination, meaning more than half of the patients experienced tumor shrinkage or halted tumor growth. This response rate significantly exceeds the 22% seen with the standard treatment, which participants in Phase 3 - Arm B will receive. The treatment blocks a protein called CD47, which cancer cells use to evade the immune system. Early findings suggest that evorpacept can enhance the effectiveness of cancer-fighting antibodies, making it a potential option for patients. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Evorpacept (ALX148)
• Paclitaxel
• Ramucirumab
• Trastuzumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Phase 3 - Arm A Experimental Treatment 4 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 A Experimental Treatment 4 Interventions

Evorpacept (ALX148) 30 mg/kg every two weeks (Q2W) intravenous (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 B Active Control 3 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 B Active Control 2 Interventions

Ramucirumab 8 mg/kg Q2W IV and paclitaxel 80 mg/m2 IV Days 1, 8, and 15 of a 28-day cycle.

Who Is Running the Clinical Trial?

ALX Oncology Inc.

Lead Sponsor

Trials

9

Recruited

1,200+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

The FEMTX-P regimen, which includes methotrexate, 5-fluorouracil, epirubicin, and cisplatin, showed a total response rate of 47% in 50 patients with advanced gastric cancer, with 11% achieving complete responses and 36% partial responses.

Despite some significant side effects, such as grade 4 leukopenia in 18% of patients, the regimen demonstrated an acceptable safety profile and a median survival of 10 months, indicating its potential effectiveness in treating this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Roelofs, EJ., Wagener, DJ., Conroy, T., et al.[2020]

In a study of 60 patients with advanced gastric cancer, the FAMTX chemotherapy regimen demonstrated similar response rates to the EAP regimen, with 33% of FAMTX patients showing a response compared to 20% for EAP.

FAMTX was found to be significantly less toxic than EAP, causing fewer instances of myelosuppression and no treatment-related deaths, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer. Kelsen, D., Atiq, OT., Saltz, L., et al.[2017]

A study involving 366 patients compared the incidence of severe hypersensitivity reactions (HSRs) during paclitaxel treatment between two premedication regimens: one including ranitidine and one without it.

The results showed that the regimen without ranitidine had a lower incidence of severe HSRs (1.6%) compared to the regimen with ranitidine (4.4%), and the non-inferiority analysis confirmed that the absence of ranitidine is just as effective in preventing severe HSRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The added value of H2 antagonists in premedication regimens during paclitaxel treatment. Cox, JM., van Doorn, L., Malmberg, R., et al.[2023]

Trastuzumab combined with chemotherapy (cisplatin and fluorouracil) significantly improves the prognosis for patients with HER2-positive gastric cancer, which is a serious subtype of gastric adenocarcinoma.

Adding pembrolizumab to trastuzumab and chemotherapy enhances the overall response rate, establishing it as the first-line treatment for HER2-positive gastric cancer, although challenges like innate resistance to trastuzumab remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advances in Treatment of Human Epidermal Growth Factor Receptor 2-Positve Gastric Cancer]. Wu, XQ., Ge, YP., Gong, XL., et al.[2022]

In a phase III trial involving predominantly female breast cancer patients receiving moderately emetogenic chemotherapy, regimens containing casopitant significantly improved the rate of complete response (no vomiting or need for rescue medications) compared to placebo, with 73-74% of patients achieving this outcome.

Casopitant was well tolerated across all treatment arms, with no significant differences in adverse events, indicating its safety as a supportive treatment for chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy. Herrstedt, J., Apornwirat, W., Shaharyar, A., et al.[2013]

Recent clinical studies indicate that using ranitidine, an H2-receptor inhibitor, is not effective in preventing hypersensitivity reactions during paclitaxel infusions, suggesting it should no longer be used for this purpose.

The editorial emphasizes the importance of moving away from non-evidence-based interventions in clinical practice, highlighting the need for treatments that are supported by solid research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No need for H2-antagonists in premedication regimens for paclitaxel infusions: less is more. Gelderblom, H., Zwaveling, J.[2021]

A 43-year-old male with recurrent HER2-overexpressing metastatic gastric cancer achieved a complete remission after receiving a novel combination of irinotecan, 5-fluorouracil, leucovorin (FOLFIRI), and trastuzumab, marking the first reported use of this regimen in third-line therapy.

The patient had previously responded well to multiple treatments, including first-line chemotherapy and surgical interventions, highlighting the potential for effective management of advanced gastric cancer with targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Weissinger, F., Reymond, M., Dumke, K., et al.[2015]

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

Chemotherapy significantly improves overall survival in patients with advanced gastric cancer by approximately 6.7 months compared to best supportive care, based on a meta-analysis of 64 randomized controlled trials involving 11,698 participants.

Combination chemotherapy offers a slight survival advantage over single-agent treatments, but this comes with increased toxicity, highlighting the need to carefully consider side effects when choosing treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced gastric cancer. Wagner, AD., Syn, NL., Moehler, M., et al.[2023]

Recent phase II and III studies have shown that combination chemotherapy regimens, such as FAMTX, EAP, and ELF, are highly effective in treating advanced gastric carcinoma, particularly in locally advanced and metastatic cases.

The FAMTX regimen has been proven superior to the previously standard treatment (FAM), with a reported resectability rate of around 50% for locally advanced disease, indicating its potential for improving surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives in chemotherapy of advanced gastric cancer. Wils, JA.[2019]

In a pilot study involving sarcoma patients undergoing multiple-day chemotherapy, a single dose of the oral antiemetic NEPA combined with dexamethasone achieved a complete response rate of 88.9% in preventing chemotherapy-induced nausea and vomiting (CINV) during the first treatment cycle.

The regimen was well tolerated, and the complete response rates remained high in subsequent cycles (88.9% for cycle 2 and 82.4% for cycle 3), indicating NEPA's efficacy and safety in managing CINV for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One shot NEPA plus dexamethasone to prevent multiple-day chemotherapy in sarcoma patients. Badalamenti, G., Incorvaia, L., Messina, C., et al.[2021]

In Korea, patients with advanced gastric cancer who undergo D2 resection benefit from postoperative adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin, indicating a potential effective treatment strategy in this population.

Trastuzumab is now part of the standard chemotherapy for gastric cancers that overexpress the HER2 protein, highlighting the importance of targeted therapies in improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced gastric cancer: review and update of current practices. Park, SC., Chun, HJ.[2023]

In a study of 1043 patients receiving paclitaxel chemotherapy, the use of H2 antagonists as part of premedication did not significantly reduce the rates of hypersensitivity reactions (HSRs), with incidences of 11.31% in the H2 antagonist group compared to 9.86% in the non-H2 antagonist group.

The findings suggest that H2 antagonists do not provide a beneficial effect in preventing HSRs during paclitaxel treatment, aligning with recent evidence that questions their role in premedication regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histamine-2 (H2 ) antagonists can be safely removed from standard paclitaxel premedication regimens. Foreman, E., Polwart, C., Walker, A., et al.[2022]

The Phase III KEYNOTE-811 study is designed to evaluate the efficacy and safety of pembrolizumab combined with trastuzumab and chemotherapy in patients with advanced HER2-positive gastric cancer, a group with limited treatment options and poor prognosis.

Pembrolizumab has shown promising antitumor activity in previous studies, suggesting that its combination with trastuzumab and chemotherapy could improve outcomes for patients with this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Chung, HC., Bang, YJ., S Fuchs, C., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.332

A phase 2/3 study of evorpacept (ALX148), a CD47 ... Background: Evorpacept (Evo) is a high affinity, CD47-blocker with an inactive Fc region designed to safely magnify anticancer antibody ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05002127

NCT05002127 | A Study of Evorpacept (ALX148) in ... This is a randomized phase 2 (open-label) / 3 (blinded), international, multi-center study of patients with metastatic HER2-overexpressing gastric/GEJ ...

3. ir.alxoncology.com ir.alxoncology.com/news-releases/news-release-details/alx-oncology-reports-positive-interim-phase-2-aspen-06-clinical

ALX Oncology Reports Positive Interim Phase 2 ASPEN-06 ... Interim efficacy results showed the confirmed overall response rate for evorpacept combination treatment was 52% compared to 22% for control treatment.

4. targetedonc.com targetedonc.com/view/evorpacept-shows-promising-efficacy-in-her2-positive-gastric-and-gej-cancers

Evorpacept Shows Promising Efficacy in HER2-Positive ... The ASPEN-06 trial found that adding evorpacept to trastuzumab, ramucirumab, and paclitaxel significantly improved overall response rates ...

5. cancernetwork.com cancernetwork.com/view/evorpacept-elicits-favorable-responses-in-her2-gastric-gej-cancer

Evorpacept Elicits Favorable Responses in HER2+ Gastric ... “[Evorpacept plus] TRP showed promising activity for patients with HER2–positive gastric and GEJ cancer with a response rate above 41.3% ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3530

Results of a phase 2 study of evorpacept (E, ALX148), ... There were two on-study deaths assessed as related to all three study drugs (hemophagocytic lymphohistiocytosis and cytokine release syndrome; 1 ...