Monoclonal Antibody Therapy for Cancer

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

151 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1/2a open-label, multicenter, dose escalation and dose expansion trial in which IMT-009 will be administered by the intravenous (IV) route to participants with solid tumors or lymphomas. The main goals of this study are to: * Find the recommended dose of IMT-009 that can be safely given to participants * Learn more about the side effects of IMT-009 * Learn more about pharmacokinetics of IMT-009 * Learn more about the effectiveness of IMT-009 * Learn more about different pharmacokinetic biomarkers and how they might change in the presence of IMT-009

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.

What data supports the effectiveness of the drug IMT-009 in cancer treatment?

Monoclonal antibodies, like IMT-009, have been shown to enhance the immune system's response against cancer cells and are used in various cancer therapies. They can prolong life and remission in certain cancers, such as colorectal cancer, and have been approved for use in multiple cancer treatments, indicating their potential effectiveness. ^{1 2 3 4 5}

Is monoclonal antibody therapy for cancer generally safe for humans?

Monoclonal antibody therapy for cancer, including treatments like immune checkpoint inhibitors, can cause immune-related side effects, which are similar to autoimmune diseases. These side effects, while rarely fatal, may require stopping the treatment or using other medications to manage them. ^{6 7 8 9 10}

What makes the drug IMT-009 unique for cancer treatment?

IMT-009 is a monoclonal antibody therapy that enhances the body's immune response against cancer by targeting specific molecules on immune cells, potentially offering additive effects when combined with conventional cancer therapies. This approach is different from traditional treatments as it leverages the immune system to fight cancer more effectively. ^{1 11 12 13 14}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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. Up to 12 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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

References

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

Potentiation of therapeutic immune responses against malignancies with monoclonal antibodies. [2017]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Overview of monoclonal antibodies in cancer therapy: present and promise. [2007]

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

Trial watch: Tumor-targeting monoclonal antibodies for oncological indications. [2021]

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

Trial Watch: Monoclonal antibodies in cancer therapy. [2021]

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report. [2022]

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

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Cancer immunotherapy-related adverse events: causes and challenges. [2021]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

The safety of therapeutic monoclonal antibodies: implications for cancer therapy including immuno-checkpoint inhibitors. [2020]

11. England pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

Role of monoclonal antibodies in tumor-specific immunity. [2019]

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

Clinical significance of CD99 down-regulation in gastric adenocarcinoma. [2017]

14. Germany pubmed.ncbi.nlm.nih.gov

Anti-human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma. [2021]