Monoclonal Antibody Therapy for Cancer
Recruiting in Palo Alto (17 mi)
+11 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Immunitas Therapeutics
Must not be taking: Investigational drugs, CYP3A4 modulators
Disqualifiers: Pregnancy, Autoimmune disease, HIV, others
No Placebo Group
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.12345
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.678910
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.111121314
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.
I am 18 years old or older.
See 1 more
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.
See 8 more
Trial 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 (Monoclonal Antibodies)
Trial OverviewThe 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
3Treatment groups
Experimental Treatment
Group I: IMT-009 Phase 2a Cohort (s)Experimental Treatment1 Intervention
Each Cohort will evaluate IMT-009 monotherapy in up to 25 Participants
Group II: IMT-009 Phase 1bExperimental Treatment2 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 EscalationExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Site 02Denver, CO
Site 03Sarasota, FL
Site 9384Austin, TX
Site 01Nashville, TN
More Trial Locations
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Who Is Running the Clinical Trial?
Immunitas TherapeuticsLead Sponsor
References
Potentiation of therapeutic immune responses against malignancies with monoclonal antibodies. [2017]Immunotherapeutic monoclonal antibodies (mAbs) can be defined as those that exert their functions by tampering with immune system cell molecules, causing an enhancement of antitumor immune responses. Some of these antibodies are agonistic ligands for surface receptors involved in the activation of lymphocytes and/or antigen-presenting cells, whereas others are antagonists of mechanisms that normally limit the intensity of immune reactions. Several mAbs of this category have been described to display in vivo antitumor activity in mouse models. Only anti-CTLA-4 (CD152) mAb has entered clinical trials, but the preclinical effects described for anti-CD40, anti-CD137 (4-1BB), anti-CD102 (intercellular adhesion molecule-2), and regulatory T cell-depleting mAbs should lead to their prompt clinical development. Their use in combination with immunizations against tumor antigens has been reported to be endowed with synergistic properties. This new group of antitumor agents holds promise for at least additive effects with conventional therapies of cancer and deserves intensive translational research.
Overview of monoclonal antibodies in cancer therapy: present and promise. [2007]After 30 years of development, therapy with monoclonal antibodies has started to realize its promise. Clinical use is most widespread in the field of oncology, where half of the agents approved for routine clinical use are employed and a large number of molecules are currently undergoing clinical trials. In the past 2 years alone, three new compounds-the radiolabeled antibody (131)I-tositumomab and two antibodies targeting growth factor receptors (bevacizumab and cetuximab)-have received FDA approval for indications in oncology. This review summarizes the development of this exciting treatment modality over the last three decades, examines the outcome of treatment with these new antibodies and others available for routine clinical use (i.e. rituximab, trastuzumab, alemtuzumab, gemtuzumab ozogamicin, (90)Y-ibritumomab tiuxetan) in standard indications and in experimental settings, and gives a brief outlook on possible future developments.
Trial watch: Tumor-targeting monoclonal antibodies for oncological indications. [2021]An expanding panel of monoclonal antibodies (mAbs) that specifically target malignant cells or intercept trophic factors delivered by the tumor stroma is now available for cancer therapy. These mAbs can exert direct antiproliferative/cytotoxic effects as they inhibit pro-survival signal transduction cascades or activate lethal receptors at the plasma membrane of cancer cells, they can opsonize neoplastic cells to initiate a tumor-targeting immune response, or they can be harnessed to specifically deliver toxins or radionuclides to transformed cells. As an indication of the success of this immunotherapeutic paradigm, international regulatory agencies approve new tumor-targeting mAbs for use in cancer patients every year. Moreover, the list of indications for previously licensed molecules is frequently expanded to other neoplastic disorders as the results of large, randomized clinical trials become available. Here, we discuss recent advances in the preclinical and clinical development of tumor-targeting mAbs for oncological indications.
Trial Watch: Monoclonal antibodies in cancer therapy. [2021]Since the advent of hybridoma technology, dating back to 1975, monoclonal antibodies have become an irreplaceable diagnostic and therapeutic tool for a wide array of human diseases. During the last 15 years, several monoclonal antibodies (mAbs) have been approved by FDA for cancer therapy. These mAbs are designed to (1) activate the immune system against tumor cells, (2) inhibit cancer cell-intrinsic signaling pathways, (3) bring toxins in the close proximity of cancer cells, or (4) interfere with the tumor-stroma interaction. More recently, major efforts have been made for the development of immunostimulatory mAbs that either enhance cancer-directed immune responses or limit tumor- (or therapy-) driven immunosuppression. Some of these antibodies, which are thought to facilitate tumor eradication by initiating or sustaining a tumor-specific immune response, have already entered clinical trials. In this Trial Watch, we will review and discuss the clinical progress of the most important mAbs that are have entered clinical trials after January 2008.
New' therapy shown to prolong life in colon cancer. [2019]Adjuvant therapy with a monoclonal antibody extends the life of and prolongs remission in people with Dukes' stage C colorectal cancer.
Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. [2019]Immunotherapy for metastatic cancer can be complicated by the onset of hepatic immune-related adverse events (IRAEs). This study compared hepatic IRAEs associated with anti-programmed cell death protein 1 (PD-1)/PD ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) monoclonal antibodies (mAbs).
Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report. [2022]The increased availability of immunotherapeutic agents for the treatment of a wide array of cancer in the general oncology practice setting will reveal rare and unique toxicities.
Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]The safety of combined immunotherapy and thoracic radiation therapy (iRT) has been understudied. We evaluated toxicities in patients receiving iRT from 3 single-institutional phase 1/2 trials.
Cancer immunotherapy-related adverse events: causes and challenges. [2021]Despite the success and ongoing promise of monoclonal antibody-targeted immune checkpoint inhibitor immunotherapy of advanced malignancies, in particular, antibodies directed against CTLA-4 and PD-1/PD-L1, the development of immune-related adverse events (irAEs) remains a constraint of this type of therapy. Although rarely fatal, the occurrence of irAEs may necessitate discontinuation of immunotherapy, as well as administration of corticosteroids or other immunosuppressive therapies that may not only compromise efficacy but also predispose for development of opportunistic infection. Clearly, retention of efficacy of immune checkpoint-targeted therapies with concurrent attenuation of immune-mediated toxicity represents a formidable challenge. In this context, the current brief review examines mechanistic relationships between these events, as well as recent insights into immunopathogenesis, and strategies which may contribute to resolving this issue. These sections are preceded by brief overviews of the discovery and functions of CTLA-4 and PD-1, as well as the chronology of the development of immunotherapeutic monoclonal antibodies which target these immune checkpoint inhibitors.
The safety of therapeutic monoclonal antibodies: implications for cancer therapy including immuno-checkpoint inhibitors. [2020]Monoclonal antibody-based treatment of cancer has been established as one of the most successful therapeutic strategies for both hematologic malignancies and solid tumors. In addition to targeting cancer antigens antibodies can also modulate immunological pathways that are critical to immune surveillance. Antibody therapy directed against several negative immunologic regulators (checkpoints) is demonstrating significant success in the past few years. Immune checkpoint inhibitors, ipilimumab, pembrolizumab and nivolumab, have shown significant clinical benefit in several malignancies and are already approved for advanced melanoma and squamous NSCLC. Based on their mechanism of action, these agents can exert toxicities that are unlike conventional cytotoxic chemotherapy, whose nature is close to autoimmune diseases - immune related adverse events (irAEs). In this review we focus on the spectrum of irAEs associated with immune checkpoint antibodies, discussing the pharmacological treatment strategy and possible clinical impact.
Monoclonal antibodies in the treatment of malignancy: basic concepts and recent developments. [2019]Antibodies have long been considered to be potential anticancer agents because of their specificity for cell-membrane antigens. Applications of hybridoma and recombinant DNA technology have led to the production of unlimited quantities of clinical-grade murine, chimeric, and humanized monoclonal antibodies for clinical use. Whole antibodies may produce anticancer effects in conjunction with the immune system by interaction with complement proteins and/or effector cells via the Fc portion of the antibody molecule. Antibodies may also neutralize circulating ligands or block cell membrane receptors and thus interrupt ligand/receptor interactions and signal transduction that are associated with proliferative or anti-apoptotic effects. The anti-idiotype network cascade provides a rationale for antibodies as vaccine therapy. Antibodies may also serve as the guiding or targeting system for other cytotoxic pharmaceutical products such as (i) radiolabeled antibodies for radioimmunodetection and radioimmunotherapy; (ii) immunotoxins; (iii) chemotherapy/antibody conjugates; (iv) cytokine/antibody conjugates; and (v) immune cell/antibody conjugates. After years of anticipation, as of late 1999 there were four monoclonal antibodies that had been approved by the U.S. Food and Drug Administration based on activity against human malignancy, all of which are in widespread clinical use. Several other products are in various stages of clinical trial testing. Monoclonal antibodies have joined interferon-alpha, interleukin-2 (IL-2), and various hematopoietic growth factors as well-established components of biological therapy, the fourth modality of cancer treatment.
Role of monoclonal antibodies in tumor-specific immunity. [2019]Monoclonal antibodies, considered to be 'magic bullets' 20 years ago, may finally be realizing their full potential, particularly in the area of oncology, where > 10 monoclonal antibodies are approved for treatment. Monoclonal antibodies are being used to modulate tumor-specific immunity through several approaches: antibodies that direct cytotoxicity against the tumor through cellular or complement-mediated pathways; antibodies that directly modulate immune regulation; antibodies that alter tolerance to tumor antigens; and antibodies that act as antigen mimetics through the anti-idiotype network. Therapeutic progress in these areas is reviewed as well as the potential to combine these approaches with standard therapies.
Clinical significance of CD99 down-regulation in gastric adenocarcinoma. [2017]CD99 is a cell adhesion molecule associated with human tumors. The aim of the present study was to characterize its role in the development and progression of human gastric adenocarcinoma.
Anti-human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma. [2021]CD99 is a surface molecule expressed on various cell types including cancer cells. Expression of CD99 on multiple myeloma is associated with CCND1-IGH fusion/t(11;14). This translocation has been reported to be a genetic hallmark of mantle cell lymphoma (MCL). MCL is characterized by overexpression of cyclin D1 and high tumor proliferation. In this study, high expression of CD99 on MCL cell lines was confirmed. Our generated anti-CD99 monoclonal antibody (mAb), termed MT99/3, exerted potent antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities against mantle B-cell lymphoma without direct cytotoxic effects. The anti-tumor activities of mAb MT99/3 were more effective in MCL than in other B-cell lymphomas. Moreover, in a mouse xenograft model using Z138 MCL cell line, treatment of mAb MT99/3 reduced tumor development and growth. Our study indicated that mAb MT99/3 is a promising immunotherapeutic candidate for mantle cell lymphoma therapy.