ICT01 for Advanced Cancers

(EVICTION Trial)

Not currently recruiting at 31 trial locations

Overseen By Katrien Lemmens, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ImCheck Therapeutics

Must not be taking: Systemic steroids

Disqualifiers: Autoimmune disorders, Immune deficiency, Infections, others

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

Compensation: Varies

Number of Visits: 11

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ICT01 (an anti-BTN3A monoclonal antibody) to determine its effectiveness for people with advanced cancers, either alone or combined with pembrolizumab (Keytruda). Researchers aim to find the optimal dose and assess how well this treatment works for various solid tumors and blood cancers. Participants should have a confirmed diagnosis of advanced cancer, such as bladder, breast, or prostate cancer, that has returned or is resistant to treatment. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive it.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop any anti-tumor drug therapy at least 28 days before starting the study treatment, unless you are receiving immune checkpoint inhibitors for the combination arm. If you are on systemic steroids above a certain dose, you must also stop them 28 days before the study.

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

Research has shown that ICT01, whether used alone or with pembrolizumab, is safe. One study found that ICT01 by itself was well-tolerated, with participants experiencing manageable side effects. In some cases, patients' cancer did not worsen, a condition known as stable disease.

When combined with pembrolizumab, ICT01 remained safe and well-tolerated. Studies have shown that some patients experienced strong and lasting positive responses, which is encouraging. The doses tested did not cause serious side effects, indicating a good safety profile.

Overall, this suggests that ICT01, both on its own and with pembrolizumab, is safe for humans based on the data collected so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment ICT01 for advanced cancers because it targets immune cells known as gamma-delta T cells, which are a unique part of the immune system not typically harnessed by current cancer therapies. Unlike the standard treatments that often focus on targeting tumor cells directly, ICT01 stimulates these immune cells to attack the cancer, potentially offering a new way to fight tumors. Additionally, the combination of ICT01 with pembrolizumab, a well-known immunotherapy drug, could enhance the immune system's response even further, potentially leading to more effective treatment outcomes.

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

Research has shown that ICT01, a treatment in this trial, activates specific immune cells called γ9δ2 T cells when used alone. These cells alter the tumor environment by activating other immune cells, potentially aiding in cancer treatment. Early results indicated that ICT01 was safe and helped some patients maintain stable disease.

Another treatment arm in this trial combines ICT01 with pembrolizumab. Studies have demonstrated that this combination produces strong and lasting responses in patients with certain types of cancers. These early findings suggest that the combination could be effective, especially for those who haven't responded to other treatments. ^{1 2 3 5 6}

Who Is on the Research Team?

Katrien Lemmens, MD, PhD

Principal Investigator

ImCheck Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with advanced-stage or recurrent cancers, including various solid tumors and blood cancers. Participants must have a certain level of immune cells (g9d2 T cells), an ECOG performance status ≤ 1, and a life expectancy over 3 months. They should not have rapidly progressing disease, active autoimmune disorders treated with immunosuppressants in the last year, primary/secondary immune deficiencies, uncontrolled infections requiring IV treatment, or recent anti-tumor therapies.

Inclusion Criteria

You have been diagnosed with advanced or recurrent cancer that falls under certain categories, including bladder, breast, colon, gastric, melanoma, ovarian, prostate, and pancreatic cancer, or certain types of leukemia and lymphoma. You must also meet certain health criteria, such as having a certain level of T cells and a life expectancy of at least three months, and have at least one measurable lesion according to specific evaluation criteria.

Voluntarily signed informed consent form.

Exclusion Criteria

I had major surgery less than 4 weeks ago.

I do not have any ongoing infections needing IV antibiotics or antivirals.

I have side effects from past treatments, but they are manageable except for some specific conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 involves dose escalation of IV ICT01 as monotherapy and in combination with pembrolizumab

12 months

Every 3 weeks

Cohort Expansion

Part 2 involves cohort expansion into specific tumor indications for ICT01 monotherapy and combination therapy

12 months

Every 8 weeks for RECIST/RECIL assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• ICT01

Trial Overview The study tests ICT01 as monotherapy and combined with pembrolizumab in patients with advanced cancer. Part 1 escalates doses to find safe levels; Part 2 expands into specific tumor types for further testing. ICT01 targets BTN3A on immune cells to potentially enhance the body's ability to fight cancer.

How Is the Trial Designed?

Group I: IV ICT01 Monotherapy Experimental Treatment 1 Intervention

Up to six ICT01 dose levels administered as IV monotherapy every 3 weeks will be tested in Part 1 Dose Escalation and up to 2 dose levels in Part 2 Cohort Expansion

Group II: IV ICT01 + IV Pembrolizumab Experimental Treatment 1 Intervention

A range of IV ICT01 doses administered every 3 weeks will be tested in combination with 200 mg pembrolizumab in Part 1 Dose Escalation and up to 2 dose levels of ICT01 plus 200 mg pembrolizumab in Part 2 Cohort Expansion

Who Is Running the Clinical Trial?

ImCheck Therapeutics

Lead Sponsor

Trials

2

Recruited

350+

Published Research Related to This Trial

BTN3A1 is expressed in most cancers and its expression level is strongly correlated with clinical outcomes in 13 different types of cancer, indicating its potential role as a prognostic biomarker.

In non-small cell lung cancer (NSCLC) and breast cancer (BRCA), BTN3A1 is often downregulated, suggesting it may act as a tumor suppressor, with its expression inversely associated with patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive analysis of BTN3A1 in cancers: mining of omics data and validation in patient samples and cellular models. Liang, F., Zhang, C., Guo, H., et al.[2022]

The study developed four fully human anti-GPC3 antibodies using a novel humanized transgenic mouse platform, demonstrating high specificity and cytotoxicity against GPC3-positive cancer cells, which are prevalent in certain cancers like hepatocellular carcinoma.

These antibodies showed strong binding affinities in the nanomolar range and effectively recognized GPC3 protein in various solid tumors, making them promising candidates for future cancer therapy research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of fully human anti-GPC3 antibodies with high-affinity recognition of GPC3 positive tumors. Yu, L., Yang, X., Huang, N., et al.[2022]

BTN3A2 is the most abundant isoform in pancreatic ductal adenocarcinoma (PDAC) and its expression is regulated by stress conditions, which may impact the tumor microenvironment.

Vγ9Vδ2 T cells require BTN3A for their anti-tumor activity against PDAC, and this activity can be significantly enhanced by the anti-BTN3A 20.1 antibody, suggesting that targeting BTN3A could be a promising strategy for immunotherapy in PDAC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC). Benyamine, A., Loncle, C., Foucher, E., et al.[2021]

The BTN3A family, particularly BTN3A1, plays a crucial role in activating Vγ9Vδ2 T cells, which are important for tumor immunity, indicating its potential as a target for cancer therapies.

BTN3A3 shows promise as a therapeutic target specifically for breast cancer, highlighting the BTN3A family's relevance in tumor prognosis and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic and Therapeutic Significance of BTN3A Proteins in Tumors. Chen, S., Li, Z., Huang, W., et al.[2021]

KTN3379, a fully human monoclonal antibody targeting HER3, effectively suppresses HER3 activity and inhibits tumor growth in various cancer models, regardless of whether HER3 activation is ligand-dependent or independent.

The study found that loss of the PTEN gene, which is common in many cancers, reduces the effectiveness of KTN3379 in HER2-amplified tumors, suggesting that patient selection for this treatment may need to consider PTEN status to enhance clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Potent HER3 Monoclonal Antibody That Blocks Both Ligand-Dependent and -Independent Activities: Differential Impacts of PTEN Status on Tumor Response. Xiao, Z., Carrasco, RA., Schifferli, K., et al.[2020]

The humanized monoclonal antibody ICT01 effectively activates Vγ9Vδ2 T cells to kill various tumor cell types while sparing normal healthy cells, demonstrating a targeted approach to cancer therapy.

In preclinical studies, ICT01 was well tolerated in cynomolgus macaques and showed promising results in delaying tumor growth and enhancing survival in mice, leading to a first-in-human clinical trial that reported good tolerance and immune activation in patients with advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of ICT01, a first-in-class, anti-BTN3A antibody for activating Vγ9Vδ2 T cell-mediated antitumor immune response. De Gassart, A., Le, KS., Brune, P., et al.[2022]

Monoclonal antibodies are a significant new class of cancer treatments that work through various mechanisms, such as blocking tumor signals, inducing cancer cell death, and enhancing the immune response, and several have been approved for use in solid tumors like breast and colorectal cancers.

Current research is focused on improving these therapies through innovative designs, identifying new targets, and developing combination strategies to enhance effectiveness and overcome treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of monoclonal antibodies as cancer therapy in solid tumors. Dienstmann, R., Markman, B., Tabernero, J.[2019]

The human antibody HN3 specifically targets glypican-3 (GPC3) with high affinity and effectively inhibits the growth of GPC3-positive hepatocellular carcinoma (HCC) cells, demonstrating its potential as a therapeutic agent.

HN3's mechanism of action involves inducing cell-cycle arrest at the G1 phase through Yes-associated protein signaling, providing new insights into GPC3-targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutically targeting glypican-3 via a conformation-specific single-domain antibody in hepatocellular carcinoma. Feng, M., Gao, W., Wang, R., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.9534

EVICTION study: ICT01, an anti-Butyrophilin 3A ... Here we present interim results from EVICTION of ICT01 in combination with pembrolizumab in patients with checkpoint inhibitor (CPI) refractory melanoma.

2. imchecktherapeutics.com imchecktherapeutics.com/pipeline/ict01/

About ICT01 As demonstrated by data presented at past AACR, ASCO, ASH, ESMO and SITC conferences, ICT01 selectively activates circulating γ9δ2 T cells ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04243499

NCT04243499 | First-in-Human Study of ICT01 in Patients ... A first-in-human, two-part clinical study to assess the safety, tolerability and activity of IV doses of ICT01 as monotherapy and in combination with a ...

4. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT179/725390/Abstract-CT179-First-in-human-study-of-ICT01-an

Abstract CT179: First-in-human study of ICT01, an anti-BTN3A ... ICT01, an anti-BTN3A mAb, selectively activates γ9δ2 T cells resulting in remodeling of the tumor microenvironment by activated γ9δ2 T, CD8 T, and NK cells.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34669444/

Development of ICT01, a first-in-class, anti-BTN3A ... Preliminary results show that ICT01 was well tolerated and pharmacodynamically active in the first patients. Digital pathology analysis of tumor ...

6. imchecktherapeutics.com imchecktherapeutics.com/all-press-release/news/imcheck-presented-updated-positive-data-from-phase-i-iia-eviction-2-trial-of-ict01-in-combination-with-low-dose-il-2-at-sitc-2023/

ImCheck Presented Updated Positive Data from Phase I/IIa ... “The data show a clear increase in γ9δ2 T cell counts as well as activation and mobilization of CD8 T cells and NK cells, indicating ICT01 in ...