COM902 for Cancer

Recruiting at 8 trial locations

Overseen By Backup COM902 ClinInfo

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Compugen Ltd

Must not be taking: TIGIT inhibitors, PVRIG inhibitors

Disqualifiers: Interstitial lung disease, Immune-related events, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Phase 1 open label sequential dose escalation and cohort expansion study evaluating the safety, tolerability and preliminary antitumor activity of COM902 as monotherapy and in combination with COM701 in subjects with advanced malignancies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug COM902 for cancer?

Research shows that COM902, an anti-TIGIT antibody, can enhance the body's immune response against tumors, especially when used with other treatments like PD-1 inhibitors. In animal studies, it helped slow down tumor growth and improved survival, suggesting it could be a promising option for treating advanced cancers. ^{1 2 3 4 5}

How is the drug COM902 different from other cancer treatments?

COM902 is unique because it targets TIGIT, an immune checkpoint that suppresses the immune system's ability to fight cancer. By blocking TIGIT, COM902 enhances the body's anti-tumor immune response, especially when used with other treatments like PD-1 inhibitors, offering a new approach for patients who do not respond to existing therapies. ^{1 2 5 6 7}

Research Team

COM902 Study Director COM902 Study Director

Principal Investigator

Compugen Ltd

Eligibility Criteria

This trial is for adults with advanced cancers like ovarian, colon, or lung cancer who've tried standard treatments without success. They should be in relatively good physical condition (ECOG 0-1) and have had no more than three prior treatment lines. People with certain immune conditions or those previously treated with specific immunotherapies are not eligible.

Inclusion Criteria

I have received PARP inhibitor therapy.

My condition is at stage IV.

I am fully active or can carry out light work.

Exclusion Criteria

I have previously been treated with specific immune-targeting medications.

I have been treated with a PVRIG inhibitor before.

I have been treated with a TIGIT inhibitor before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

COM902 monotherapy administered IV every 3 weeks in sequential dose escalation to identify maximum tolerated dose or recommended dose for expansion

Up to 18 months

Every 3 weeks

Cohort Expansion

COM902 + COM701 combination and triplet combinations evaluated in subjects with select tumor types

Up to 24 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• COM902 (TIGIT Inhibitor)

Trial Overview The study tests COM902 alone and in combinations: as a monotherapy, paired with COM701, and alongside both COM701 and Pembrolizumab. It's to see how safe they are and if they can shrink tumors. The doses will increase until researchers find the highest dose patients can take without serious side effects.

Participant Groups

Group I: Platinum resistant ovarian cancer Triplet combination (COM902 + COM701 + Pembrolizumab). Experimental Treatment 1 Intervention

Triplet combination of COM902 + COM701 + Pembrolizumab evaluated in subjects with PROC. All study drugs will be administered IV every 3 weeks.

Group II: MSS-CRC Triplet combination (COM902 + COM701 + Pembrolizumab). Experimental Treatment 1 Intervention

Triplet combination of COM902 + COM701 + Pembrolizumab evaluated in subjects with MSS-CRC. All study drugs will be administered IV every 3 weeks.

Group III: Dual combination (COM902 + COM701) for evaluation of safety/tolerability (both at RDFE). Experimental Treatment 1 Intervention

COM902 will be combined with COM701 for evaluation of safety and tolerability. All study drugs will be administered IV every 3 weeks.

Group IV: COM902 monotherapy dose escalation. Experimental Treatment 1 Intervention

Monotherapy dose escalation. COM902 monotherapy administered IV every 3 weeks in sequential dose escalation. Up to 7 dose escalation cohorts may be evaluated until a maximum tolerated dose or recommended dose for expansion (RDFE) is identified.

Group V: COM902 monotherapy cohort expansion at RDFE. Experimental Treatment 1 Intervention

COM902 monotherapy at the RDFE - in subjects with multiple myeloma. COM902 will be administered IV every 3 weeks.

Group VI: COM902 + COM701 combination cohort expansion both at RDFE. Experimental Treatment 1 Intervention

COM902 + COM701 (both at the RDFE) evaluated in subjects with select tumor types who have exhausted standard of care treatment: HNSCC, CRC (MSS), NSCLC. All study drugs will be administered IV every 3 weeks.

Who Is Running the Clinical Trial?

Compugen Ltd

Lead Sponsor

Trials

5

Recruited

540+

Findings from Research

TIGIT is expressed on various immune cells, including Tregs and γδ T cells, with the highest density found in tumor-infiltrating Tregs, suggesting that targeting TIGIT could enhance immune responses against tumors.

The use of antagonistic anti-TIGIT mAbs, like EOS-448, not only restores T-cell function but also directly kills TIGIT-expressing tumor cells, indicating a promising therapeutic strategy for treating hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoration of T-cell Effector Function, Depletion of Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT Antagonist Antibodies. Preillon, J., Cuende, J., Rabolli, V., et al.[2021]

TIGIT is a co-inhibitory receptor found on T cells that is upregulated in various tumors, making it a potential target for enhancing cancer immunotherapy.

The newly developed anti-TIGIT antibody, COM902, has shown promise in boosting immune responses against tumors in laboratory studies and mouse models, suggesting it could be an effective treatment for advanced cancers when used alone or in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade. Hansen, K., Kumar, S., Logronio, K., et al.[2021]

CD155 and TIGIT are overexpressed in colorectal cancer (CRC), leading to suppressed anti-cancer immunity by reducing the activity of CD8+ T cells that secrete important cytokines.

Blocking TIGIT enhances the immune response against CRC by increasing cytokine secretion from CD8+ T cells and activating the NF-κB signaling pathway, suggesting a potential therapeutic strategy for CRC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD155/TIGIT signaling regulates the effector function of tumor-infiltrating CD8+ T cell by NF-κB pathway in colorectal cancer. Li, S., Ding, J., Wang, Y., et al.[2022]

Increased expression of TIGIT in patients with solid cancers is significantly linked to poorer overall survival and relapse-free survival, indicating that TIGIT may play a detrimental role in anti-tumor immunity.

The study suggests that combining PD-1 and TIGIT blockade could be a promising strategy to enhance treatment efficacy, as there is a strong association between TIGIT and PD-1 expression, which may help overcome immune resistance seen with single-agent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers. Hosseinkhani, N., Shadbad, MA., Asghari Jafarabadi, M., et al.[2021]

Anti-TIGIT antibodies show promising activity in treating non-small cell lung cancer (NSCLC), especially when used in combination with anti-PD-1/PD-L1 therapies, with ongoing phase 3 trials to confirm these results.

Preliminary data suggest that anti-TIGIT treatment may lead to better patient responses when combined with other checkpoint inhibitors, indicating its potential as an effective new option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of Anti-TIGIT Antibodies for Immunotherapy of Cancer. Florou, V., Garrido-Laguna, I.[2022]

CD96 and TIGIT are inhibitory receptors on T and NK cells that can negatively impact immune responses, with CD96 knockout mice showing enhanced NK-cell activity and tumor resistance, suggesting their potential as targets for cancer therapy.

Blocking CD96 or TIGIT with monoclonal antibodies has been shown to improve tumor control in mice, especially when combined with PD-1/PD-L1 blockade, indicating promising strategies for developing new immuno-oncology treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy. Blake, SJ., Dougall, WC., Miles, JJ., et al.[2021]

A panel of nine nanobodies targeting TIGIT was developed, showing excellent binding affinity and specificity for detecting TIGIT expression in tumors, which could help in patient stratification for anti-TIGIT therapies.

In vivo studies demonstrated that these nanobodies had significantly higher uptake in TIGIT-overexpressing tumors compared to controls, indicating their potential as effective noninvasive imaging agents to monitor TIGIT levels and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and evaluation of nanobody tracers for noninvasive nuclear imaging of the immune-checkpoint TIGIT. Zeven, K., De Groof, TWM., Ceuppens, H., et al.[2023]

References

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

Restoration of T-cell Effector Function, Depletion of Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT Antagonist Antibodies. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade. [2021]

3. Australia pubmed.ncbi.nlm.nih.gov

CD155/TIGIT signaling regulates the effector function of tumor-infiltrating CD8+ T cell by NF-κB pathway in colorectal cancer. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis on the Significance of TIGIT in Solid Cancers: Dual TIGIT/PD-1 Blockade to Overcome Immune-Resistance in Solid Cancers. [2021]

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

Clinical Development of Anti-TIGIT Antibodies for Immunotherapy of Cancer. [2022]

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

Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Development and evaluation of nanobody tracers for noninvasive nuclear imaging of the immune-checkpoint TIGIT. [2023]