IDP-023 + Antibody Therapies for Blood Cancers

Recruiting at 10 trial locations

Overseen By Indapta Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Indapta Therapeutics, INC.

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

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called IDP-023 for individuals with certain advanced blood cancers. Researchers are testing IDP-023 alone and in combination with other medications to assess its safety and effectiveness in fighting cancer. The trial includes different groups for people with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL), both types of blood cancer. It suits individuals with MM who have tried at least three other treatments or those with NHL who have tried at least two, without success. Participants should also be able to carry out daily activities with little or no assistance. As a Phase 1, Phase 2 trial, this study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer research.

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.

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

Research has shown that IDP-023 is safe and well-tolerated at various doses, with some patients responding positively. Early studies reported no serious safety issues.

Existing research supports the safety of isatuximab, rituximab, and daratumumab in combination treatments. Isatuximab effectively treats multiple myeloma with manageable side effects. Rituximab is well-known for treating non-Hodgkin lymphoma and is generally well-tolerated. Daratumumab is safely used in multiple myeloma treatments and helps slow cancer progression when combined with standard therapies.

Overall, past studies have shown these treatments to be well-tolerated, and using them together aims to enhance effectiveness while maintaining safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about IDP-023 for blood cancers because it offers a fresh approach compared to standard treatments like chemotherapy, which often comes with harsh side effects. IDP-023 is unique because it can be used alone or in combination with antibodies like isatuximab, rituximab, and daratumumab, potentially enhancing effectiveness and targeting cancer cells more precisely. This versatility may offer a more tailored and potentially more effective treatment option for patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Additionally, the combination of IDP-023 with immune system boosters like IL-2 could further enhance the body's ability to fight cancer, making it a promising candidate in the fight against these challenging diseases.

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

Research has shown that IDP-023 shows early promise in treating blood cancers like multiple myeloma and non-Hodgkin lymphoma. Initial tests indicate that patients tolerate it well, whether used alone or with interleukin-2, a protein that can boost the immune system.

This trial includes several treatment arms. In one arm, IDP-023 combines with isatuximab, which has improved treatment results in multiple myeloma, with isatuximab alone achieving a 26.3% success rate in difficult cases. Another arm combines IDP-023 with rituximab, which has a 48% success rate in some non-Hodgkin lymphoma patients when used alone.

Lastly, an arm uses daratumumab, another antibody treatment, with IDP-023, known to improve survival rates in multiple myeloma patients. These combinations aim to enhance treatment effectiveness by employing different methods to attack cancer cells. ^{1 2 3 6 7}

Who Is on the Research Team?

Indapta Therapeutics, Inc.

Principal Investigator

Indapta Therapeutics, INC.

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Daratumumab
• Fludarabine
• IDP-023
• Interleukin-2
• Mesna
• Rituximab

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.

How Is the Trial Designed?

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

IDP-023 is already approved in United States for the following indications:

Approved in United States as IDP-023 for:

• None - Currently under investigation for Non-Hodgkin lymphoma and multiple myeloma

Who Is Running the Clinical Trial?

Indapta Therapeutics, INC.

Lead Sponsor

Trials

2

Recruited

160+

Published Research Related to This Trial

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 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]

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]

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 study highlights the effectiveness of a radio-labeled humanized anti-CD33 monoclonal antibody (M195) in reducing acute myeloid leukemia (AML) cells in relapsed patients and eliminating minimal residual disease in patients with acute promyelocytic leukemia (APL) in remission.

The humanized version of M195 showed improved binding and function compared to the original murine antibody, with preliminary trials indicating successful targeting of bone marrow without causing an immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD33 monoclonal antibody M195 for the therapy of myeloid leukemia. Caron, PC., Scheinberg, DA.[2019]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. jitc.bmj.com jitc.bmj.com/content/12/Suppl_3/A1713

1483 Activity of IDP-023 allogeneic g-NK cells without ... Conclusions IDP-023 was well tolerated in both every week x3 and every other day x3 regimens. Encouraging initial activity was observed with IDP ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06119685

Study Details | NCT06119685 | IDP-023 as a Single Agent ... This is an open label, Phase 1/2, first-in-human, multiple ascending dose, and dose-expansion study of IDP-023 administered as a single agent and in combination ...

3. neurologylive.com neurologylive.com/view/fda-clears-indapta-therapeutics-ind-cell-therapy-idp-023-progressive-ms

FDA Clears Indapta Therapeutics' IND for Cell Therapy IDP ... IDP-023 is also under investigation in a phase 1/2 trial for multiple myeloma and non-Hodgkin lymphoma, with promising early results. One of ...

4. myeloma.org myeloma.org/sparkcures/trial/1794/tel%3A/description

IDP-023 This is an open label, Phase 1/2, first-in-human, multiple ascending dose, and dose-expansion study of IDP-023 administered as a single agent and in combination ...

5. firstwordpharma.com firstwordpharma.com/story/5910585

Indapta Therapeutics Presents Clinical and Preclinical ... Patients received one to three doses of IDP-023, with or without interleukin-2 (IL-2). The treatment was generally well-tolerated, with no dose ...

6. bloodcancerstoday.com bloodcancerstoday.com/post/idp-023-receives-fast-track-designation-from-fda

IDP-023 Receives Fast Track Designation From FDA Participants will receive up to three planned doses of IDP-023 with or without interleukin-2 to evaluate safety. Subsequently, patients will ...

7. targetedonc.com targetedonc.com/view/fda-fast-tracks-idp-023-for-non-hodgkin-lymphoma-and-myeloma

FDA Fast Tracks IDP-023 for Non-Hodgkin Lymphoma and ... The natural killer cell therapy IDP-023 is being studied in a phase 1 trial for the treatment of patients with non-Hodgkin lymphoma and multiple myeloma.