Monoclonal Antibody Therapy for Cancer

Not currently recruiting at 11 trial locations

Overseen By Immunitas Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Immunitas Therapeutics

Must not be taking: Investigational drugs, CYP3A4 modulators

Disqualifiers: Pregnancy, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IMT-009, a monoclonal antibody therapy, for individuals with certain cancers that have not responded to other treatments. The trial aims to determine the safest dose, understand potential side effects, and evaluate the treatment's effectiveness. It involves participants with specific cancers such as lung, breast, or esophageal cancer, who have undergone certain past treatments but still experience progression. Participants must have a type of tumor that meets specific criteria and be willing to undergo particular medical evaluations. As a Phase 1 trial, this research focuses on understanding 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 protocol does not specify if you must stop taking your current medications. However, you cannot be on any cancer therapy or investigational drugs while participating in the study.

Is there any evidence suggesting that IMT-009 is likely to be safe for humans?

Research has shown that IMT-009, a monoclonal antibody treatment, appears promising in early studies. IMT-009 targets CD161, a component of certain immune cells, potentially enhancing the body's ability to fight cancer.

In early animal studies, IMT-009 was well-tolerated, indicating it did not cause serious side effects. However, human testing is crucial because reactions can differ. This trial is in its early stages, focusing on identifying a safe dose and understanding any side effects.

As a Phase 1/2 trial, the primary goal is to determine a safe dose and learn about side effects in humans. Early trials like this often involve more unknowns, and participants might experience some side effects as the treatment's safety is still being assessed.

Overall, while early results are promising, human trials will provide clearer information about safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cancer?

Most treatments for cancer work by targeting rapidly dividing cells, which can lead to side effects as they also affect healthy cells. But IMT-009 is different; it uses a monoclonal antibody that specifically targets cancer cells, potentially reducing collateral damage to healthy tissues. Researchers are excited about IMT-009 because of its precision in targeting, as well as its ability to work in combination with the standard care drug fruquintinib. This combination could enhance treatment effectiveness and improve patient outcomes compared to existing options.

What evidence suggests that IMT-009 might be an effective treatment for cancer?

Research shows that IMT-009, a monoclonal antibody, could effectively treat cancer. Studies have found that it can disrupt a specific process that aids cancer growth. This disruption enhances the body's immune response against cancer cells. Early research confirms that IMT-009 improves immune cells' ability to attack tumors, making it a promising option for treating lymphomas and other solid tumors. In this trial, participants may receive IMT-009 as monotherapy or combined with the standard of care, fruquintinib. Initial results suggest it might work well alone or with other treatments. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors or lymphomas that are progressing, have failed previous treatments, or when standard care isn't an option. Participants must not be on current cancer therapy and should not have serious heart conditions, active infections like HIV/Hepatitis B/C, certain autoimmune diseases, CNS metastases unless stable, or a recent history of severe allergic reactions to monoclonal antibodies.

Inclusion Criteria

My cancer did not respond or stopped responding to previous anti-PD-L1 treatment.

I have a specific type of solid tumor or lymphoma and have received the detailed treatments.

My cancer is advanced, cannot be surgically removed, and has not responded to or I cannot undergo standard treatments.

Exclusion Criteria

I have a history of or currently have HIV, Hepatitis B, or C.

I had cancer before, but it's been cured and there's been no sign of it for 3 years.

I haven't taken systemic treatment for an autoimmune disease in the last 6 months, except for stable hypothyroidism, vitiligo, resolved asthma or alopecia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive IMT-009 monotherapy in dose escalation to determine the recommended dose

21 days per cycle

Multiple visits per cycle

Phase 1b

Participants receive IMT-009 in combination with standard of care fruquintinib

28 days per cycle

Multiple visits per cycle

Phase 2a

Evaluation of IMT-009 monotherapy in different cohorts

21 days per cycle

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after treatment discontinuation

What Are the Treatments Tested in This Trial?

Interventions

• IMT-009

Trial Overview

The trial is testing IMT-009's safety and dosage in patients with various cancers. It's an early-stage study (Phase 1/2a) involving multiple centers where participants receive the drug intravenously. Researchers will observe how the body processes IMT-009 and its effectiveness against cancer.

How Is the Trial Designed?

Group I: IMT-009 Phase 2a Cohort (s) Experimental Treatment 1 Intervention

Each Cohort will evaluate IMT-009 monotherapy in up to 25 Participants

Group II: IMT-009 Phase 1b Experimental Treatment 2 Interventions

Participants will receive an assigned dose level of IMT-009 in combination with standard of care fruquintinib. Approximately 18 Participants will be enrolled in the Phase 1b portion of the study.

Group III: IMT-009 Dose Escalation Experimental Treatment 1 Intervention

Participants will receive an assigned dose level of IMT-009 monotherapy in dose escalation. Up to 64 Participants will be enrolled in the Phase 1 portion of the study.

Who Is Running the Clinical Trial?

Immunitas Therapeutics

Lead Sponsor

Trials

1

Recruited

150+

Published Research Related to This Trial

Monoclonal antibodies have become a significant tool in cancer treatment, with over 10 approved therapies that enhance the body's immune response against tumors.

These antibodies work through various mechanisms, including directing immune cells to attack tumors, modulating immune regulation, and potentially improving the effectiveness of standard cancer treatments when combined with them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of monoclonal antibodies in tumor-specific immunity. Nicodemus, CF., Smith, LM., Schultes, BC.[2019]

The study confirmed that CD99 is highly expressed on mantle cell lymphoma (MCL) cell lines, which is associated with aggressive tumor characteristics like high proliferation and cyclin D1 overexpression.

The anti-CD99 monoclonal antibody (mAb) MT99/3 demonstrated strong anti-tumor effects through mechanisms like antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), significantly reducing tumor growth in a mouse model of MCL, suggesting its potential as an effective immunotherapy for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma. Takheaw, N., Sittithumcharee, G., Kariya, R., et al.[2021]

In a study of 536 patients undergoing immunotherapy for metastatic cancer, only 3.5% developed severe hepatitis, indicating that while hepatic immune-related adverse events (IRAEs) can occur, they are relatively rare and often not severe.

Histological analysis of liver biopsies revealed distinct patterns of liver injury associated with different immunotherapies, allowing for tailored management strategies that do not always require systemic corticosteroids, thus minimizing unnecessary treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. De Martin, E., Michot, JM., Papouin, B., et al.[2019]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

Monoclonal antibody therapies targeting CTLA-4 and PD-1/PD-L1 have shown promise in treating advanced cancers, but they can lead to immune-related adverse events (irAEs) that may require treatment discontinuation and the use of corticosteroids, which can reduce the therapy's effectiveness.

Understanding the mechanisms behind irAEs and exploring strategies to mitigate these side effects is crucial for maintaining the efficacy of immune checkpoint inhibitors while minimizing immune-mediated toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer immunotherapy-related adverse events: causes and challenges. Blidner, AG., Choi, J., Cooksley, T., et al.[2021]

Monoclonal antibody treatments, particularly immune checkpoint inhibitors like ipilimumab, pembrolizumab, and nivolumab, have shown significant success in treating various cancers, including advanced melanoma and squamous non-small cell lung cancer (NSCLC).

These therapies can cause unique immune-related adverse events (irAEs) that differ from traditional chemotherapy side effects, resembling autoimmune diseases, which necessitates careful management and understanding of their clinical impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of therapeutic monoclonal antibodies: implications for cancer therapy including immuno-checkpoint inhibitors. Demlova, R., Valík, D., Obermannova, R., et al.[2020]

In a patient with cutaneous squamous cell cancer and a cardiac allograft, PD-1 antibody therapy led to acute cellular rejection characterized by a high presence of activated CD8+ T cells, indicating a unique toxicity associated with immunotherapy in transplant recipients.

High-intensity immunosuppression successfully reversed the graft rejection, allowing the patient to maintain cardiac function and survive for 7 months after stopping the PD-1 inhibitor nivolumab, suggesting that while immune checkpoint inhibitors can be harmful in allograft patients, effective management strategies exist.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report. Owonikoko, TK., Kumar, M., Yang, S., et al.[2022]

Monoclonal antibodies have been developed using advanced technologies and are now available in clinical-grade forms, showing potential as effective anticancer agents by targeting specific cell-membrane antigens.

As of late 1999, four monoclonal antibodies were FDA-approved for treating human cancers, demonstrating their efficacy and safety, and they are now considered a key part of biological therapy alongside other treatments like interferon-alpha and IL-2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies in the treatment of malignancy: basic concepts and recent developments. Dillman, RO.[2019]

In a study of 283 gastric adenocarcinoma cases, decreased expression of the cell adhesion molecule CD99 was linked to poor survival rates and negative clinical outcomes, indicating its potential role as a prognostic marker.

The down-regulation of CD99 was associated with promoter methylation and loss of heterozygosity, as well as reduced expression of the transcription factor SP1, suggesting that these molecular changes contribute to the progression of gastric adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical significance of CD99 down-regulation in gastric adenocarcinoma. Lee, JH., Kim, SH., Wang, LH., et al.[2017]

Monoclonal antibodies (mAbs) can enhance antitumor immune responses by either activating immune cells or blocking mechanisms that suppress immune reactions, showing promising antitumor activity in mouse models.

While only anti-CTLA-4 has reached clinical trials, other mAbs like anti-CD40 and anti-CD137 show potential for clinical development, especially when used alongside tumor antigen immunizations for improved efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potentiation of therapeutic immune responses against malignancies with monoclonal antibodies. Murillo, O., Arina, A., Tirapu, I., et al.[2017]

Monoclonal antibody therapy has become a significant treatment option in oncology, with half of the approved agents being used in this field and many more in clinical trials.

Recently, three new monoclonal antibodies, including (131)I-tositumomab, bevacizumab, and cetuximab, received FDA approval, highlighting the ongoing advancements and potential of this treatment modality in cancer care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of monoclonal antibodies in cancer therapy: present and promise. Stern, M., Herrmann, R.[2007]

Monoclonal antibodies (mAbs) are increasingly being used in cancer therapy, targeting malignant cells and blocking survival signals, which can lead to direct cancer cell death and stimulate immune responses against tumors.

Regulatory agencies are approving new mAbs annually, and existing ones are being repurposed for additional cancer types as new clinical trial results emerge, highlighting their growing role in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial watch: Tumor-targeting monoclonal antibodies for oncological indications. Vacchelli, E., Pol, J., Bloy, N., et al.[2021]

Adjuvant therapy using a monoclonal antibody has been shown to significantly extend survival and prolong remission in patients with Dukes' stage C colorectal cancer.

This treatment approach highlights the potential of targeted therapies in improving outcomes for patients with advanced colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New' therapy shown to prolong life in colon cancer. [2019]

Monoclonal antibodies (mAbs) have become essential tools in cancer therapy, with several approved by the FDA in the last 15 years, designed to either activate the immune system against tumors or inhibit cancer cell signaling pathways.

Recent advancements focus on immunostimulatory mAbs that enhance immune responses against cancer, with some already in clinical trials, indicating a promising direction for more effective cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial Watch: Monoclonal antibodies in cancer therapy. Galluzzi, L., Vacchelli, E., Fridman, WH., et al.[2021]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S000649712309417X

Anti CD161 Antibody IMT-009 Is a Novel ...

Our results support evaluation of IMT-009 as a novel cancer immunotherapy to disrupt CLEC2D/CD161 signaling, with strong therapeutic potential in lymphomas.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05565417

Study of the Monoclonal Antibody IMT-009 in Patients With ...

Preclinical data confirm that CD161 blockade with IMT-009 results in enhanced anti-tumor activity. This is a Phase 1/2a, open label dose escalation study of IMT ...

3.

prnewswire.com

prnewswire.com/news-releases/immunitas-therapeutics-presents-preclinical-data-supporting-combination-of-imt-009-with-anti-pd1-immunotherapy-at-the-aacr-2024-annual-meeting-302109948.html

Immunitas Therapeutics Presents Preclinical Data ...

IMT-009 has been shown to restore the anti-cancer activity of T and NK cells in preclinical studies by blocking interactions between CD161 and its ligand, CLEC ...

4.

jitc.bmj.com

jitc.bmj.com/content/10/Suppl_2/A1383

1332 Anti-CD161 antibody IMT-009 is a novel ...

Conclusions These results support the development of IMT-009 as a novel cancer immunotherapy for application in several solid tumor indications.

5.

immunitastherapeutics.squarespace.com

immunitastherapeutics.squarespace.com/s/Conf_Immunitas-SITC-Data-Release_FINAL.pdf

Novel cancer immunotherapeutic agent IMT-009 with a ...

Preclinical data confirm that CD161 blockade with. IMT-009 results in enhanced anti-tumor activity. IMT-009 is anticipated to begin ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05565417

Study of the Monoclonal Antibody IMT-009 in Patients With ...

IMT-009 is an Fc-attenuated monoclonal antibody that binds with high affinity and selectivity to CD161, a receptor that is broadly expressed on NK and a subset ...

7.

bloodcancerunited.org

bloodcancerunited.org/resources/newsroom/immunitas-therapeutics-announces-first-patient-dosed-phase-12a-study-imt-009

Immunitas Therapeutics Announces First Patient Dosed in ...

The Phase 1 study (NCT05565417) is designed to evaluate the safety, tolerability, pharmacodynamic biomarkers, and preliminary efficacy of IMT-009 as well as ...

8.

immunitastherapeutics.squarespace.com

immunitastherapeutics.squarespace.com/s/Anti-CD161-antibody-IMT-009.pdf

Anti-CD161 antibody IMT-009 is a novel ...

• The results described above support the development of IMT-009 as a novel cancer immunotherapy for application in several solid tumor indications and ...

9.

firstwordpharma.com

firstwordpharma.com/story/5833880

Immunitas Therapeutics to Present Preclinical Data ...

The Phase 1 study is designed to evaluate the safety, tolerability, pharmacodynamic biomarkers, and preliminary efficacy of IMT-009 as well as ...