VERT-002 for Solid Tumors

Recruiting at 17 trial locations

Overseen By Medical Officer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pierre Fabre Medicament

Must not be taking: Corticosteroids, others

Disqualifiers: CNS metastases, ILD, cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 4

140 Participants Needed

Trial Summary

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 must not have taken a MET TKI within 7 days or any other systemic anticancer therapy within 14 to 28 days before starting the trial. It's best to discuss your current medications with the trial team to be sure.

How is the drug VERT-002 different from other treatments for solid tumors?

VERT-002 is unique because it involves the activation of peroxisome proliferator-activated receptors (PPARs), which are part of a group of nuclear receptors that can influence cell growth and differentiation. This mechanism is different from traditional chemotherapy, which typically targets rapidly dividing cells directly. ^{1 2 3 4 5}

What is the purpose of this trial?

The goal of this clinical trial is to investigate the safety, the activity of VERT-002, and the optimal safe dose to be used, in participants with solid tumors including non-small cell lung cancer.

Eligibility Criteria

This trial is for individuals with advanced or widespread solid tumors, including non-small cell lung cancer, that have specific genetic changes known as MET alterations. Details on who can join are not fully provided.

Inclusion Criteria

My cancer has a specific genetic change (METex14 mutation) or one of several MET alterations.

My liver is working well.

My cancer has returned or didn't respond to treatment and has spread, with no standard treatment left.

Exclusion Criteria

I have not had major surgery within the last 14 days.

I do not have uncontrolled brain metastases or worsening spinal cord compression.

I have not received a live vaccine in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

VERT-002 administered via IV infusion every 2 weeks with 4 provisional doses planned

8 weeks

4 visits (in-person)

Preliminary Activity Assessment

One dose and schedule selected from Part 1 for further assessment

4-8 weeks

Dose Range Optimization

2 or 3 doses and schedule selected from Part 1 to determine OBD and MTD/MAD

4-8 weeks

Dose Expansion

Dose expansion at RP2D to be defined later

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• VERT-002

Trial Overview The study is testing VERT-002 to find a safe and effective dose and see how well it works in treating certain types of cancers with genetic alterations.

Participant Groups

Group I: VERT-002 Experimental Treatment 1 Intervention

Part 1: Dose escalation (Phase Ia): VERT-002 will be administered via intravenous (IV) infusion every 2 weeks. 4 provisional doses are planned. An alternative regimen may be tested informed by the emerging data Part 2a: Preliminary Activity Assessment (Phase Ib): One dose \& schedule selected from Part 1 Part 2b: Dose range optimization (Phase Ib): 2 or 3 doses \& schedule selected from Part 1: From the lower limit \[Optimal Biologically Active Dose (OBD)\] \& upper limit \[Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) if MTD is not reached\] Part 3: Dose Expansion at RP2D (Phase II): To be defined later on

Who Is Running the Clinical Trial?

Pierre Fabre Medicament

Lead Sponsor

Trials

83

Recruited

90,400+

Marie-Andrée Gamache

Pierre Fabre Medicament

Chief Executive Officer

MBA from HEC Montréal

Dr. Núria Perez-Cullell

Pierre Fabre Medicament

Chief Medical Officer since 2022

PhD in Pharmacy from the University of Barcelona

Findings from Research

In a study of 28 surgical sections of human chondrosarcoma, 67.9% of tumor cells showed positive immunoreaction for peroxisome proliferator-activated receptor-gamma (PPAR-gamma), indicating its potential role in the disease's development.

The PPAR-gamma ligands, particularly 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), were found to inhibit the proliferation of chondrosarcoma cells and induce apoptosis, suggesting they could be promising therapeutic agents for treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-gamma. Nishida, K., Furumatsu, T., Takada, I., et al.[2018]

The study found that two PPARbeta/delta ligands, GW0742 and GW501516, did not promote cancer cell growth or increase markers associated with tumorigenesis, such as Akt phosphorylation, VEGF, or COX2 expression, in various human cancer cell lines.

In vivo analysis in mice also showed no changes in liver, colon, or colon polyps after administration of these ligands, suggesting that PPARbeta/delta ligands do not enhance tumorigenesis, contradicting some previous reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands do not potentiate growth of human cancer cell lines. Hollingshead, HE., Killins, RL., Borland, MG., et al.[2022]

PPARdelta is consistently expressed in both normal and cancerous gastric tissues, indicating its potential role in gastric carcinogenesis, as shown through various methods including RT-PCR and immunohistochemistry.

The study found that inhibiting COX-2 with the specific inhibitor NS398 led to a reduction in PPARdelta expression in gastric cancer cells with high COX-2 levels, suggesting that COX-2 inhibitors may help prevent cancer by suppressing PPARdelta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of peroxisome proliferator-activated receptor delta in human gastric cancer and its response to specific COX-2 inhibitor. Yu, J., Leung, WK., Chen, J., et al.[2006]

Vitamin D(3) and its analogs, along with PPARgamma ligands, have shown promising results as differentiating agents in the treatment of prostate cancer, highlighting their potential therapeutic roles.

Both classes of drugs target the vitamin D(3) receptor and PPARs, which are commonly expressed in prostate cancer cells, suggesting a mechanism of action that could enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiating agents and the treatment of prostate cancer: Vitamin D3 and peroxisome proliferator-activated receptor gamma ligands. Leibowitz, SB., Kantoff, PW.[2019]

Activation of the PPARdelta receptor by selective agonists significantly stimulates the growth of breast and prostate cancer cell lines, indicating a potential role in cancer progression.

The study suggests that PPARdelta may promote cellular proliferation and angiogenesis through an autocrine loop involving increased expression of growth factors like VEGFalpha, highlighting the therapeutic potential of PPARdelta antagonists in treating these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of peroxisome proliferator-activated receptor delta stimulates the proliferation of human breast and prostate cancer cell lines. Stephen, RL., Gustafsson, MC., Jarvis, M., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-gamma. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands do not potentiate growth of human cancer cell lines. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Expression of peroxisome proliferator-activated receptor delta in human gastric cancer and its response to specific COX-2 inhibitor. [2006]

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

Differentiating agents and the treatment of prostate cancer: Vitamin D3 and peroxisome proliferator-activated receptor gamma ligands. [2019]

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

Activation of peroxisome proliferator-activated receptor delta stimulates the proliferation of human breast and prostate cancer cell lines. [2019]