COM503 + Zimberelimab for Cancer

Recruiting at 3 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

Trial Summary

What is the purpose of this trial?

The overall goal of this first-in-human (FIH) clinical trial is to learn about the safety and dosing of COM503 when given alone or in combination with zimberelimab in participants with advanced solid tumors. The primary objectives of this study are: * To assess the safety and tolerability of COM503 as monotherapy and COM503 in combination with zimberelimab in participants with advanced solid tumors. * To identify the maximum tolerated dose (MTD) / maximum administered dose (MAD) and/or the recommended phase 2 dose (RP2D) of COM503 as monotherapy and in combination with zimberelimab in participants with advanced solid tumors.

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.

What data supports the effectiveness of the drug COM503 + Zimberelimab for cancer?

Zimberelimab has been approved in China for treating a type of lymphoma (a cancer of the lymphatic system) based on positive results from a clinical trial. Additionally, COM701, a similar drug, has shown early signs of effectiveness in treating various advanced cancers, suggesting potential benefits when combined with other treatments like Zimberelimab. ^{1 2 3 4 5}

What makes the drug COM503 + Zimberelimab unique for cancer treatment?

The combination of COM503 and Zimberelimab is unique because it involves Zimberelimab, an anti-PD-1 antibody, which helps the immune system recognize and attack cancer cells. This approach is part of a newer class of treatments called immune checkpoint inhibitors, which have shown promise in treating various cancers by enhancing the body's immune response against tumors. ^{1 6 7 8 9}

Eligibility Criteria

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 cancer is advanced, recurrent, or has spread to other parts.

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

My condition worsened despite all standard treatments.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Zimberelimab: First Approval. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

U3-1402 sensitizes HER3-expressing tumors to PD-1 blockade by immune activation. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of MEDI0562, a Humanized OX40 Agonist Monoclonal Antibody, in Adult Patients with Advanced Solid Tumors. [2021]

7. United States 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors: Key trials and an emerging role in breast cancer. [2022]

9. United States 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. [2022]