IPH4502 for Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Innate Pharma

Must not be taking: CYP 3A4 inhibitors, inducers

Disqualifiers: Brain metastases, Active infection, Cardiovascular disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a first-in-human, open-label, multicenter, Phase 1 study to evaluate the safety, tolerability and preliminary efficacy of IPH4502 and to determine the recommended Phase 2 dose (RP2D) in advanced solid tumors that are known to express Nectin-4

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic corticosteroids, immunosuppressive agents, and specific CYP 3A4 inhibitors or inducers, at least 14 days before starting the study drug. If you are on these medications, you may need to stop or adjust them before participating.

What data supports the effectiveness of the drug IPH4502 for cancer?

Research on similar treatments, like immune checkpoint inhibitors, shows they can be effective in treating various cancers by helping the immune system attack cancer cells. For example, ipilimumab, a similar drug, has improved survival in advanced melanoma and other cancers. ^{1 2 3 4 5}

How does the drug IPH4502 differ from other cancer treatments?

IPH4502 may target IDH2, a protein involved in cancer cell metabolism and growth, which is not commonly targeted by existing cancer treatments. This approach could offer a novel way to inhibit cancer cell proliferation by disrupting their metabolic processes. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for patients with advanced solid tumors that express a protein called Nectin-4. Specific eligibility details are not provided, but typically participants must be adults with measurable disease who have tried standard treatments without success.

Inclusion Criteria

Measurable disease according to RECIST 1.1

My cancer is advanced, cannot be surgically removed, and tests positive for Nectin-4.

I've had treatment for advanced cancer, but nothing available works for my cancer type.

Exclusion Criteria

I started blood thinner treatment for a clot less than 14 days ago.

Participants with clinically significant comorbidity(s)

I do not have any active infections requiring systemic treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 involves dose escalation guided by a Bayesian optimal interval design with backfilling (BOIN-BF) to determine the safety, tolerability, and pharmacokinetics of IPH4502

Variable

Dose Optimization

Part 2 involves dose optimization in up to 2 selected indications to further evaluate the safety and efficacy of IPH4502

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Treatment Details

Interventions

• IPH4502 (Monoclonal Antibodies)

Trial Overview The study is testing the safety and how well patients tolerate IPH4502, a new potential cancer treatment. It's also looking at early signs of its effectiveness against tumors. The goal is to find the best dose to use in future Phase 2 trials.

Participant Groups

Group I: IPH4502 Monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Innate Pharma

Lead Sponsor

Trials

29

Recruited

3,100+

Findings from Research

The combination of immune checkpoint inhibitors (ICIs) and anti-VEGF therapy significantly improves overall survival (OS) and progression-free survival (PFS) in patients with unresectable or advanced liver cancer, based on an analysis of 8 clinical trials.

While this combination treatment shows promising efficacy, it is associated with higher risks of serious adverse events, particularly affecting the urinary, cardiovascular, and blood systems, necessitating careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of immune checkpoint inhibitors combined with anti-VEGF therapy in the treatment of unresectable or advanced liver cancer: a systematic review. Yang, W., Li, X., He, J., et al.[2023]

Ipilimumab, a first-in-class T-cell potentiator, has shown significant improvements in overall survival for advanced melanoma patients in a phase 3 trial, with median survival extending to 10.1 months compared to 6.4 months for the control group.

The treatment demonstrated long-term survival benefits, with 24-month survival rates increasing from 13.7% with the gp100 vaccine alone to 21.6% and 23.5% for patients receiving ipilimumab alone or in combination, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Releasing the brake on the immune system: ipilimumab in melanoma and other tumors. Tarhini, A., Lo, E., Minor, DR.[2021]

Immune checkpoint inhibitors (ICPI) significantly improve overall survival across various solid cancers, with a hazard ratio of 0.74, indicating a 26% reduction in the risk of death compared to standard treatments.

While ICPIs are generally well tolerated and show better side effect profiles than traditional chemotherapy, the use of PD-L1 expression as a biomarker for directing ICPI therapy is questionable, suggesting the need for further research into alternative biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors efficacy across solid cancers and the utility of PD-L1 as a biomarker of response: a systematic review and meta-analysis. Fitzsimmons, TS., Singh, N., Walker, TDJ., et al.[2023]

In a study involving 3697 patients with advanced hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICIs) demonstrated a median overall survival of 12.0 months and a median progression-free survival of 4.9 months, indicating their efficacy in treating this cancer.

Combining ICIs with anti-vascular endothelial growth factor (VEGF) agents resulted in improved survival outcomes, with a median overall survival of 16.4 months, while maintaining a manageable safety profile, as only 28% experienced grade 3 or higher adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of immune checkpoint inhibitors in advanced hepatocellular carcinoma: a meta-analysis based on 40 cohorts incorporating 3697 individuals. Wang, R., Lin, N., Mao, B., et al.[2022]

In a phase 3 trial involving 1150 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab with two cycles of chemotherapy significantly improved overall survival compared to chemotherapy alone, with a median survival of 15.6 months versus 10.9 months.

The treatment regimen showed a favorable safety profile, with serious treatment-related adverse events occurring in 30% of the experimental group compared to 18% in the control group, indicating that the benefits of the combination therapy outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Paz-Ares, L., Ciuleanu, TE., Cobo, M., et al.[2021]

Wild-type isocitrate dehydrogenase 2 (IDH2) is crucial for protecting colorectal cancer (CRC) cells from oxidative damage, and its suppression leads to increased DNA damage and cell senescence.

Inhibiting IDH2 not only reduces CRC cell growth but also makes these cells more sensitive to DNA-damaging drugs like oxaliplatin, suggesting a potential new strategy for cancer treatment by targeting metabolic pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wild-type IDH2 protects nuclear DNA from oxidative damage and is a potential therapeutic target in colorectal cancer. Qiao, S., Lu, W., Glorieux, C., et al.[2023]

The study identified the IDH2 rs11540478 genetic variant as a new risk factor for lung cancer, showing that carriers of the TT and CT genotypes have a 44% higher risk compared to CC carriers, based on an analysis of 262 lung cancer patients and 602 healthy controls.

Functional analysis revealed that the T allele of rs11540478 is associated with increased IDH2 expression and higher lung cancer cell viability, suggesting that this genetic variant may play a significant role in the development of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new functional IDH2 genetic variant is associated with the risk of lung cancer. Li, J., Lu, J., He, Y., et al.[2022]

The study identified IGF2 as a crucial factor in the development of anal squamous cell carcinoma (ASCC), with alterations in the IGF2 and related genes occurring in about 60% of cases, indicating a potential target for therapy.

IGF2, secreted by cancer-associated fibroblasts, promotes the growth of ASCC cells, suggesting that targeting the IGF2/IGF1R pathway could be a promising strategy for developing new treatments for this cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between IGF2-PI3K axis and cancer-associated-fibroblasts promotes anal squamous carcinogenesis. Cacheux, W., Lièvre, A., Richon, S., et al.[2020]

The combination of activated Notch signaling, loss of p53, and the IDH1R132C mutation in mice led to the development of intrahepatic cholangiocarcinoma (ICC), demonstrating a clear oncogenic potential of the IDH1R132C mutation.

In contrast, other combinations of these factors did not result in tumor formation, indicating that the specific interaction of NICD, shP53, and IDH1R132C is crucial for ICC development, which was confirmed by the presence of histological features similar to human ICCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncogenic potential of IDH1R132C mutant in cholangiocarcinoma development in mice. Ding, N., Che, L., Li, XL., et al.[2018]

Wild-type IDH2 is up-regulated in lung cancer and is associated with poor survival outcomes, indicating its potential role as a biomarker for cancer prognosis.

Targeting IDH2 with specific inhibitors or shRNA reduces HIF1α expression, leading to decreased lung cancer cell proliferation and tumor growth, suggesting that IDH2 could be a promising therapeutic target in lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wild-type IDH2 promotes the Warburg effect and tumor growth through HIF1α in lung cancer. Li, J., He, Y., Tan, Z., et al.[2022]

References

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

Efficacy and safety of immune checkpoint inhibitors combined with anti-VEGF therapy in the treatment of unresectable or advanced liver cancer: a systematic review. [2023]

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

Releasing the brake on the immune system: ipilimumab in melanoma and other tumors. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors efficacy across solid cancers and the utility of PD-L1 as a biomarker of response: a systematic review and meta-analysis. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

The efficacy of immune checkpoint inhibitors in advanced hepatocellular carcinoma: a meta-analysis based on 40 cohorts incorporating 3697 individuals. [2022]

5. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Wild-type IDH2 protects nuclear DNA from oxidative damage and is a potential therapeutic target in colorectal cancer. [2023]

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

A new functional IDH2 genetic variant is associated with the risk of lung cancer. [2022]

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

Interaction between IGF2-PI3K axis and cancer-associated-fibroblasts promotes anal squamous carcinogenesis. [2020]

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

Oncogenic potential of IDH1R132C mutant in cholangiocarcinoma development in mice. [2018]

10. Australia pubmed.ncbi.nlm.nih.gov

Wild-type IDH2 promotes the Warburg effect and tumor growth through HIF1α in lung cancer. [2022]