IDP-023 + Antibody Therapies for Blood Cancers

Recruiting at 13 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Indapta Therapeutics, INC.

Disqualifiers: Cardiac disease, HIV, Hepatitis, SARS-CoV-2, others

No Placebo Group

Breakthrough Therapy

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests IDP-023, a treatment using special immune cells to fight cancer, in patients with advanced multiple myeloma or non-Hodgkin's lymphoma who haven't responded to other treatments. IDP-023 is part of a broader category of immunotherapies that have shown promise in treating multiple myeloma and non-Hodgkin's lymphoma.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug IDP-023 + Antibody Therapies for Blood Cancers?

Monoclonal antibodies (mAbs), which are part of this treatment, have been shown to be effective in treating blood cancers by targeting specific molecules on cancer cells, leading to their destruction. These antibodies can work by directly killing cancer cells or by helping the immune system to attack them more effectively. ^{1 2 3 4 5}

What safety data exists for IDP-023 and antibody therapies for blood cancers?

Drugs for blood cancers, like those in this trial, often have safety updates after approval, with many experiencing changes in warnings and side effects. Common serious side effects include low white blood cell counts, infections, and digestive issues. It's important to monitor for unrecognized side effects when using these treatments. ^{6 7 8 9 10}

How is the drug IDP-023 unique in treating blood cancers?

IDP-023 is unique because it is combined with antibody therapies to enhance the body's immune response against blood cancers, potentially offering a more targeted and effective treatment compared to traditional therapies. This approach leverages the body's own T-cells to attack cancer cells, which is a novel strategy in the treatment of hematologic malignancies. ^{2 11 12 13 14}

Research Team

Indapta Therapeutics, Inc.

Principal Investigator

Indapta Therapeutics, INC.

Eligibility Criteria

This trial is for adults with advanced blood cancers like Non-Hodgkin's Lymphoma or Multiple Myeloma who have tried at least two or three treatments without success. They should be relatively healthy otherwise, with a life expectancy over 12 weeks and able to perform daily activities with little to no assistance.

Inclusion Criteria

I have multiple myeloma that has not responded to 3 or more treatments.

I have non-Hodgkin lymphoma that didn't respond to at least 2 chemotherapy treatments.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I am currently infected with COVID-19.

I have heart problems or a history of significant heart disease.

I have HIV, active hepatitis B, or hepatitis C.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

The primary objectives are to define the safety of different IDP-023 containing regimens and to define the recommended regimen and Phase 2 doses (RP2D) of IDP-023.

up to 1 year

Multiple visits for dose escalation and monitoring

Phase 2: Expansion

Evaluate the safety and efficacy of IDP-023 in advanced MM in combination with isatuximab or daratumumab and advanced NHL in combination with rituximab.

2 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Cyclophosphamide (Alkylating agents)
• Daratumumab (Monoclonal Antibodies)
• Fludarabine (Anti-metabolites)
• IDP-023 (Monoclonal Antibodies)
• Interleukin-2 (Cytokine)
• Mesna (Other)
• Rituximab (Monoclonal Antibodies)

Trial Overview The study tests IDP-023 alone and combined with other drugs (Rituximab, Daratumumab) in different stages. It aims to find the safest dose that works best against these cancers. Some patients will also receive IL-2, Cyclophosphamide, Fludarabine, and Mesna as part of their treatment combinations.

Participant Groups

Group I: Phase 2: Combination IDP-023 plus rituximab Experimental Treatment 6 Interventions

NHL patients treated with multiple doses of IDP-023 in combination with rituximab

Group II: Phase 2: Combination IDP-023 plus isatuximab Experimental Treatment 6 Interventions

MM patients treated with multiple doses of IDP-023 in combination with isatuximab

Group III: Phase 2: Combination IDP-023 plus daratumumab Experimental Treatment 6 Interventions

MM patients treated with multiple doses of IDP-023 in combination with daratumumab

Group IV: Phase 1: Single Agent IDP-023 - Single Dose Experimental Treatment 4 Interventions

NHL or MM patient treated with a single dose of IDP-023 monotherapy

Group V: Phase 1: Single Agent IDP-023 - Multiple Doses with IL-2 Experimental Treatment 5 Interventions

NHL and MM patients treated with multiple doses of IDP-023 monotherapy

Group VI: Phase 1: Single Agent IDP-023 - Multiple Doses Experimental Treatment 4 Interventions

NHL and MM patients treated with multiple doses of IDP-023 monotherapy

Who Is Running the Clinical Trial?

Indapta Therapeutics, INC.

Lead Sponsor

Trials

2

Recruited

160+

Findings from Research

Monoclonal antibodies (mAbs) are effective treatments for various cancers, targeting key components of tumor growth and their environment, such as VEGF and HER2.

Recent advancements in genetic engineering and understanding of cancer biology have led to the development of new mAbs that are currently in clinical trials, which may significantly improve patient outcomes and survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies as therapeutics in human malignancies. Pandey, M., Mahadevan, D.[2014]

The anti-Pgp/anti-CD3 diabody effectively targets and lyses drug-resistant leukemia cells, showing a binding rate of 86.25% to Jurkat cells and 86.26% to K562/A02 cells, indicating strong specificity for these cancer cells.

In a human leukemia nude mice xenograft model, the diabody inhibited tumor growth by 98.57% and significantly prolonged the survival of mice, demonstrating its potential as a powerful therapeutic agent against drug-resistant leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Specific targeting cytotoxicity to resistant leukemia cells mediated by anti-Pgp/anti-CD3 diabody]. Gao, YD., Xiong, DS., Yang, M., et al.[2018]

Monoclonal antibodies (mAbs) are effective treatments for hematological diseases, utilizing mechanisms like complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) to target and kill cancer cells while minimizing side effects.

Recent advancements, such as defucosylated mAbs that enhance ADCC and the development of antibody-drug conjugates, are improving the efficacy of mAbs, suggesting a promising future for these therapies in treating blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic monoclonal antibodies for hematological diseases]. Harada, T., Abe, M.[2014]

Brentuximab vedotin is a CD30-specific antibody-drug conjugate that effectively targets and delivers cytotoxic agents to malignant cells in classical Hodgkin's lymphoma, showing significant clinical activity in patients with relapsed disease.

The drug is well-tolerated, making it a promising candidate for incorporation into standard treatment strategies for Hodgkin's lymphoma, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in Hodgkin's lymphoma. Pro, B., Perini, GF.[2019]

A review of 35 new drugs for hematological malignancies revealed that 80% had postmarketing safety-related label modifications, indicating that many drugs may have unrecognized side effects after approval.

Most of these drugs were approved based on limited evidence, with 77% not supported by randomized controlled trials, highlighting the need for caution among hematologists when prescribing these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies. Gafter-Gvili, A., Tibau, A., Raanani, P., et al.[2020]

Idelalisib, when combined with rituximab or bendamustine, showed promising efficacy in treating relapsed/refractory indolent non-Hodgkin lymphoma, with overall response rates of 75% to 88% across different treatment combinations in a study of 79 patients.

Despite the initial positive results, the study also noted significant adverse events, such as neutropenia and pneumonia, highlighting the potential for increased toxicity in later phase trials, which suggests caution in interpreting early phase data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinations of idelalisib with rituximab and/or bendamustine in patients with recurrent indolent non-Hodgkin lymphoma. de Vos, S., Wagner-Johnston, ND., Coutre, SE., et al.[2019]

New drugs and biologics for treating hematologic malignancies were approved between late 2020 and late 2021, including CAR T-cell therapies, which utilize the body's immune cells to target cancer.

The discussion emphasized the importance of understanding the mechanisms of action and safety profiles of these therapies to ensure safe and effective patient management by advanced practitioners.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2020-2021 Drug Updates in Hematologic Malignancies. Hanna, K.[2022]

The PI3K pathway is crucial in cancer progression and immune response, and several PI3K inhibitors, including idelalisib, copanlisib, duvelisib, and umbralisib, have been approved for treating hematological malignancies.

This review highlights a lack of real-world data on the incidence and gastrointestinal toxicity, specifically colitis, associated with PI3K inhibitors, emphasizing the need for better understanding and management of these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Gastro-Intestinal Toxicity of the Pi3 Kinase Inhibitor: Optimizing Future Dosing Strategies. Breal, C., Beuvon, F., de Witasse-Thezy, T., et al.[2023]

In a retrospective study of 110 patients with chronic lymphocytic leukaemia (CLL) treated with idelalisib and rituximab, the overall response rate was high at 88.2%, with front-line patients showing an even better response of 96.3%.

While idelalisib demonstrated clear efficacy, it was associated with significant discontinuation rates (87.3%), primarily due to adverse events, particularly in front-line patients, highlighting the need for careful management of known toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective observational study to evaluate the clinical outcomes and routine management of patients with chronic lymphocytic leukaemia treated with idelalisib and rituximab in the UK and Ireland (RETRO-idel). Eyre, TA., Preston, G., Kagdi, H., et al.[2021]

The CD19xCD3 DART bispecific antibody effectively eliminates B-cell malignancies, showing rapid or slow tumor cell killing depending on patient subsets, with delayed responses manageable through prolonged treatment.

This approach generates both CD4+ and CD8+ cytotoxic T-cells, leading to significant expansion and effective targeting of neoplastic B-cells, demonstrating its potential as a tailored therapy for conditions like B-Acute Lymphoblast Leukemia and Diffuse Large B Cell Lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailoring CD19xCD3-DART exposure enhances T-cells to eradication of B-cell neoplasms. Circosta, P., Elia, AR., Landra, I., et al.[2021]

The anti-CD20 x anti-CD3 bispecific diabody effectively binds to both B cells and T cells, demonstrating its potential to mediate tumor cell lysis and inhibit tumor growth, as shown in vitro and in animal models.

In experiments with human peripheral blood lymphocytes, the diabody significantly improved survival rates in mice with human B-lymphoma, indicating its promising clinical application for treating CD20-positive B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient inhibition of human B-cell lymphoma xenografts with an anti-CD20 x anti-CD3 bispecific diabody. Xiong, D., Xu, Y., Liu, H., et al.[2019]

Active immunization with the idiotype (Id) of non-Hodgkin's lymphoma cells can generate a broad immune response that targets both the original tumor and its mutated variants, potentially preventing relapse.

In a study using mice, various forms of immunization (including proteins and genetic vaccines) successfully elicited a specific immune response against tumor-derived Id proteins, suggesting this approach could be effective in treating patients who relapse with mutated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idiotype vaccines for non-Hodgkin's lymphoma induce polyclonal immune responses that cover mutated tumor idiotypes: comparison of different vaccine formulations. Caspar, CB., Levy, S., Levy, R.[2021]

The CD3×CD123 DART molecule effectively redirects T cells to target and kill acute myeloid leukemia (AML) cells, demonstrating significant binding and activation of T cells in preclinical studies.

This bispecific antibody approach shows dose-dependent efficacy in killing both AML cell lines and primary AML blasts, supporting its potential for clinical testing in patients with CD123(+) AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD123 in acute myeloid leukemia using a T-cell-directed dual-affinity retargeting platform. Al-Hussaini, M., Rettig, MP., Ritchey, JK., et al.[2021]

References

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

Monoclonal antibodies as therapeutics in human malignancies. [2014]

2. China pubmed.ncbi.nlm.nih.gov

[Specific targeting cytotoxicity to resistant leukemia cells mediated by anti-Pgp/anti-CD3 diabody]. [2018]

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

Anti-CD33 monoclonal antibody M195 for the therapy of myeloid leukemia. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

[Therapeutic monoclonal antibodies for hematological diseases]. [2014]

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

Brentuximab vedotin in Hodgkin's lymphoma. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies. [2020]

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

Combinations of idelalisib with rituximab and/or bendamustine in patients with recurrent indolent non-Hodgkin lymphoma. [2019]

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

2020-2021 Drug Updates in Hematologic Malignancies. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Management of Gastro-Intestinal Toxicity of the Pi3 Kinase Inhibitor: Optimizing Future Dosing Strategies. [2023]

10. England pubmed.ncbi.nlm.nih.gov

A retrospective observational study to evaluate the clinical outcomes and routine management of patients with chronic lymphocytic leukaemia treated with idelalisib and rituximab in the UK and Ireland (RETRO-idel). [2021]

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

Tailoring CD19xCD3-DART exposure enhances T-cells to eradication of B-cell neoplasms. [2021]

12. Ireland pubmed.ncbi.nlm.nih.gov

Efficient inhibition of human B-cell lymphoma xenografts with an anti-CD20 x anti-CD3 bispecific diabody. [2019]

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

Idiotype vaccines for non-Hodgkin's lymphoma induce polyclonal immune responses that cover mutated tumor idiotypes: comparison of different vaccine formulations. [2021]

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

Targeting CD123 in acute myeloid leukemia using a T-cell-directed dual-affinity retargeting platform. [2021]