COM503 + Zimberelimab for Cancer

Recruiting at 5 trial locations

Overseen By Michelle Chief Medical Officer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Compugen Ltd

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: CNS metastases, Active infections, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of a new treatment, COM503, used alone or with zimberelimab (an immunotherapy) for people with advanced solid tumors. Researchers seek to identify the optimal dose and assess tolerance. This trial may suit individuals with solid tumors unresponsive to other treatments or for whom other treatments are unsuitable. Participants must have a tumor measurable by scans like CT or MRI. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take immunosuppressive medications like high-dose steroids within 2 weeks before starting the trial.

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

Research shows that COM503 and its combination with zimberelimab remain in the early testing stages. Limited information exists on how people react to these treatments. As a Phase 1 study, the primary goal is to assess safety and determine the correct dose. This phase typically involves a small number of participants and focuses mainly on safety.

Detailed reports on how well participants handle these treatments or any specific side effects are not yet available. However, zimberelimab is already used in other treatments, suggesting it might be safe, though this combination is still under study. Participants considering this trial should understand that the focus is on evaluating safety and identifying the optimal dosage. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about COM503 and Zimberelimab because they represent a novel approach to cancer treatment. Unlike traditional therapies that might focus on directly killing cancer cells, COM503 uniquely targets specific pathways involved in cancer cell survival and proliferation, potentially leading to more effective cancer control with fewer side effects. Zimberelimab, on the other hand, is an immune checkpoint inhibitor that helps the body's immune system recognize and attack cancer cells, offering a different mechanism of action compared to standard chemotherapy. Together, these treatments could provide a powerful one-two punch against cancer, offering hope for better patient outcomes.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that COM503, one of the treatments in this trial, yields promising results in treating advanced solid tumors when used alone. In earlier studies, 44% of patients experienced disease stabilization, with some even seeing tumor reduction. Patients who responded well to the treatment had an average of 10.5 months before disease progression. In this trial, some participants will receive COM503 combined with zimberelimab, another treatment option under study. The combination has demonstrated activity against tumors, suggesting enhanced effectiveness. These early findings indicate that COM503, either alone or with zimberelimab, could help manage advanced solid tumors. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with advanced solid tumors who are interested in testing a new treatment. Participants should be adults willing to provide tissue samples and have no prior treatments that would interfere with the study.

Inclusion Criteria

My disease worsened after standard treatment, or standard treatments were not suitable for me.

My condition worsened despite all standard treatments.

My solid tumor can be measured by CT or MRI.

Exclusion Criteria

Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the participant's participation in the trial

I haven't had any cancer besides non-dangerous skin cancer or fully removed early-stage cancer in the last 2 years.

I haven't taken high doses of steroids or similar medications in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of COM503 as monotherapy or in combination with zimberelimab to assess safety and determine the maximum tolerated dose

8-12 weeks

Dose Expansion

Participants receive COM503 at the determined dose level as monotherapy or in combination with zimberelimab to further evaluate safety and tolerability

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• COM503
• Zimberelimab

Trial Overview The trial is evaluating the safety, tolerability, and optimal dosing of COM503 alone or combined with zimberelimab. It aims to find the highest dose patients can take without serious side effects.

How Is the Trial Designed?

Group I: Part 2, B Experimental Treatment 2 Interventions

Dose expansion, COM503 in combination with a fixed dose of zimberelimab.

Group II: Part 2, A Experimental Treatment 1 Intervention

Dose expansion, COM503 monotherapy

Group III: Part 1, B Experimental Treatment 2 Interventions

Dose escalation, COM503 in combination with a fixed dose of zimberelimab.

Group IV: Part 1, A-2 Experimental Treatment 1 Intervention

Backfill

Group V: Part 1, A-1 Experimental Treatment 1 Intervention

Monotherapy Dose Escalation

Who Is Running the Clinical Trial?

Compugen Ltd

Lead Sponsor

Trials

5

Recruited

540+

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

This trial aims to compare the effectiveness of pembrolizumab combined with chemotherapy versus pembrolizumab alone in patients with advanced non-small-cell lung cancer who have high PD-L1 expression (≥50%).

The study expects that the combination treatment will lead to a lower risk of early disease progression and a higher objective tumor response, providing insights into long-term benefits for patients not eligible for other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression ≥50. Descourt, R., Chouaid, C., Pérol, M., et al.[2021]

MEDI0562, an agonistic antibody targeting the OX40 costimulatory molecule, was safely administered to 55 patients with advanced solid tumors, showing a tolerable safety profile with treatment-related adverse events occurring in 67% of patients, primarily fatigue and infusion reactions.

The treatment demonstrated some antitumor activity, with 44% of patients achieving stable disease and two patients showing partial responses, alongside evidence of enhanced T-cell proliferation, indicating potential effectiveness in boosting immune responses against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of MEDI0562, a Humanized OX40 Agonist Monoclonal Antibody, in Adult Patients with Advanced Solid Tumors. Glisson, BS., Leidner, RS., Ferris, RL., et al.[2021]

In the JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

Immune checkpoint inhibitors are promising immunomodulatory agents that help reactivate immune cells to fight tumors, showing significant effectiveness in treating solid cancers like melanoma and non-small cell lung cancer.

Numerous clinical studies are currently investigating the benefits of these inhibitors across various cancer types, with a particular focus on their application in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer. Gaynor, N., Crown, J., Collins, DM.[2022]

Zimberelimab is an anti-PD-1 monoclonal antibody that has been approved in China for treating relapsed or refractory classical Hodgkin's lymphoma based on a successful phase II trial.

The drug is being developed for various cancers, including cervical cancer and non-small cell lung cancer, highlighting its potential broad application in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zimberelimab: First Approval. Markham, A.[2022]

U3-1402, an antibody-drug conjugate targeting HER3, demonstrated significant antitumor effects in a mouse model resistant to PD-1 therapy by directly killing tumor cells and enhancing immune cell infiltration.

The combination of U3-1402 with PD-1 inhibition significantly improved antitumor immunity, suggesting that U3-1402 could be an effective partner in immunotherapy for patients with solid tumors resistant to PD-1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U3-1402 sensitizes HER3-expressing tumors to PD-1 blockade by immune activation. Haratani, K., Yonesaka, K., Takamura, S., et al.[2020]

In a phase I study involving 58 patients with advanced solid tumors, the combination of MEDI0562 with either durvalumab or tremelimumab showed moderate toxicity, with 74.1% and 67.7% of patients reporting treatment-related adverse events, respectively.

While three patients showed a partial response to the MEDI0562 and durvalumab combination, the study did not demonstrate clear efficacy signals, indicating that further research is needed to evaluate the effectiveness of these combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors. Goldman, JW., Piha-Paul, SA., Curti, B., et al.[2022]

The immune checkpoint inhibitor COM701, which targets the PVRIG protein, has demonstrated early signs of effectiveness in treating advanced solid tumors in an ongoing phase I trial.

COM701 shows potential for enhanced efficacy when used in combination with nivolumab, suggesting a promising approach for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COM701 Shows Antitumor Activity, +/- Nivolumab. [2021]

Combining anti-OX40 and anti-CTLA-4 monoclonal antibody immunotherapy enhances the survival of cancer patients by boosting the expansion and function of effector T cells.

Blocking IL-4 alongside this combination therapy further improves anti-tumor effectiveness, suggesting that targeting multiple pathways can enhance cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined OX40 ligation plus CTLA-4 blockade: More than the sum of its parts. Linch, SN., Redmond, WL.[2021]

Citations

1. ir.cgen.com ir.cgen.com/news-and-events/news/news-details/2025/Compugen-Announces-First-Patient-Dosed-in-Phase-1-Clinical-Trial-to-Evaluate-COM503-as-Monotherapy-and-in-Combination-with-Zimberelimab-in-Advanced-Solid-Tumors/default.aspx

News Details The first patient was dosed in a Phase 1 clinical trial with COM503, a potential first-in-class antibody against IL-18 binding protein licensed by Compugen to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06759649?intr=COM503&rank=1

A Clinical Trial to Assess COM503 in Participants With ... A structured online system, such as the ClinicalTrials.gov results database, that provides the public with access to registration and summary results ...

3. prnewswire.com prnewswire.com/news-releases/compugen-reports-third-quarter-2025-results-302610022.html

Compugen Reports Third Quarter 2025 Results ... cancer patients, with a median progression-free survival of 10.5 months in patients who derived clinical benefit. The data also showed that ...

4. ainvest.com ainvest.com/news/compugen-announces-human-trial-com503-advanced-solid-malignancies-2510/

Compugen Announces First-in-Human Trial for COM503 ... Compugen, a clinical-stage cancer immunotherapy company, announced that a trial in progress of its first-in-human clinical trial assessing ...

5. withpower.com withpower.com/trial/com503-zimberelimab-for-cancer-710ed

COM503 + Zimberelimab for Cancer The treatment demonstrated some antitumor activity, with 44% of patients achieving stable disease and two patients showing partial responses, alongside evidence ...

6. jitc.bmj.com jitc.bmj.com/content/13/Suppl_2/A670

589 A first in human clinical trial to assess the anti-IL18BP ... The primary objectives are to assess the safety and tolerability of COM503 as monotherapy and in combination with zimberelimab and identify ...

7. ctv.veeva.com ctv.veeva.com/study/a-clinical-trial-to-assess-com503-in-participants-with-advanced-solid-malignancies

A Clinical Trial to Assess COM503 in Participants With ... The primary objectives of this study are: To assess the safety and tolerability of COM503 as monotherapy and COM503 in combination with ...

8. prnewswire.com prnewswire.com/news-releases/compugen-announces-fda-clearance-of-ind-for-com503-for-the-treatment-of-solid-tumors-302208442.html

Compugen Announces FDA Clearance of IND for COM503 ... FDA clearance triggers a $30 million milestone payment from Gilead; Company on track to initiate a Phase 1 trial for COM503, ...