COM902 for Cancer

Not currently recruiting at 8 trial locations

Overseen By Backup COM902 ClinInfo

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Compugen Ltd

Must not be taking: TIGIT inhibitors, PVRIG inhibitors

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

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment called COM902 (an Anti-TIGIT antibody), either alone or with other drugs, to determine its safety and effectiveness against certain advanced cancers. It targets patients who have not responded to other treatments. The trial includes groups with specific cancers, such as multiple myeloma, colorectal cancer, and ovarian cancer. Participants must have a confirmed advanced solid tumor and have exhausted standard treatment options. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that COM902 is well tolerated in early studies. In animal studies, COM902 proved safe even at high doses, suggesting potential safety for humans.

Studies have demonstrated that the combination of COM902 and COM701 is well tolerated. Patients with difficult-to-treat cancers have shown positive responses to this combination without major safety concerns.

When combined with pembrolizumab, COM902 and COM701 have yielded promising results. This combination was well tolerated, and patients exhibited good responses.

As this study is in an early phase, it focuses on ensuring the treatment's safety for humans. Prospective participants should know that researchers closely monitor for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about COM902 because it represents a novel approach to cancer treatment, particularly in challenging cases like head and neck, colorectal, and non-small cell lung cancers. Unlike traditional chemotherapy or radiation, which target rapidly dividing cells, COM902 is an immune checkpoint inhibitor that works by unleashing the body's own immune system to fight cancer cells more effectively. This treatment is often combined with COM701 and Pembrolizumab to enhance its efficacy, offering a potentially more powerful and targeted attack against tumors. This innovative strategy is noteworthy for its potential to overcome resistance seen with standard treatments, offering hope for improved outcomes in patients who have exhausted conventional options.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that COM902, an anti-TIGIT antibody, helps the immune system fight cancer. In this trial, participants may receive COM902 alone or with other treatments. Studies have found that combining COM902 and COM701 can strengthen the body's immune response and may help shrink tumors. In some trial arms, adding pembrolizumab, which helps immune cells attack cancer, to this combination has produced promising results in patients with difficult-to-treat cancers, such as ovarian and colorectal cancer. Early results suggest these combinations can lead to long-lasting treatment effects. While more research is needed, these findings offer hope that COM902 could effectively treat advanced cancers. ^{3 4 6 7 8}

Who Is on the Research Team?

COM902 Study Director COM902 Study Director

Principal Investigator

Compugen Ltd

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• COM902

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04354246

Study Details | NCT04354246 | COM902 (A TIGIT Inhibitor) ... Phase 1 open label sequential dose escalation and cohort expansion study evaluating the safety, tolerability and preliminary antitumor activity of COM902

2. withpower.com withpower.com/trial/phase-1-multiple-myeloma-2-2020-7dfba

COM902 for Cancer · Info for Participants Research shows that COM902, an anti-TIGIT antibody, can enhance the body's immune response against tumors, especially when used with other treatments like ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10249258/

Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer ... Preclinical studies have demonstrated the potential benefits of co-inhibition of TIGIT and PD-1/PD-L1 in enhancing anti-tumor immunity and improving treatment ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10992303/

COM902, a novel therapeutic antibody targeting TIGIT ... We explored the therapeutic potential of targeting TIGIT by generating COM902, a fully human anti-TIGIT hinge-stabilized IgG4 monoclonal ...

5. cgen.com cgen.com/wp-content/uploads/SITC-2021-COM902-e-poster-1016-2021-aha.pdf

COM902 (Anti-TIGIT antibody) monotherapy COM902 Recommended dose for expansion. •. Patients with advanced solid malignancies including pts with multiple myeloma. COM902 + COM701 Safety/Tolerability.

6. prnewswire.com prnewswire.com/il/news-releases/compugen-to-present-anti-tumor-activity-and-safety-data-of-com701-com902-and-pembrolizumab-combination-in-patients-with-platinum-resistant-ovarian-cancer-at-sitc-2024-302296418.html

Compugen to Present Anti-Tumor Activity and Safety Data ... COM701 in combination with COM902 (Fc reduced anti-TIGIT) and pembrolizumab (anti-PD-1) resulted in durable objective responses in late-stage ...

7. cgen.com cgen.com/pipeline/com902-tigit/

COM902/Anti-TIGIT antibody Preclinical data indicate that treatment with COM902 enhances T cell activation and increases anti-tumor immune responses. Additional preclinical data show a ...

8. clin.larvol.com clin.larvol.com/trial-detail/NCT04354246

COM902 (A TIGIT Inhibitor) in Subjects With Advanced ... "'The pooled analysis demonstrates that COM701 was well tolerated and showed consistent, durable responses in patients with heavily pretreated ...