ISB 1442 for Multiple Myeloma

No longer recruiting at 16 trial locations

Overseen By Ichnos Sciences Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ichnos Sciences SA

Must not be taking: Anti-CD38, CD47 therapies

Disqualifiers: Minimal residual disease, Plasmacytoma, CNS involvement, 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 ISB 1442, administered as a subcutaneous (SC) injection, for individuals with multiple myeloma—a type of blood cancer that has returned or not responded to standard treatments. The research aims to determine if ISB 1442 is safe and effective by starting with low doses and gradually increasing them. Participants who have already tried at least three different therapies, such as proteasome inhibitors and immunomodulators, without success might be suitable candidates. 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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received anti-CD38 antibodies or CD47 targeted therapies within 1 month before the trial starts, or systemic anticancer treatments within 14 days before the first dose. Hormonal therapy for prostate or breast cancer, bisphosphonates, and certain other treatments are allowed.

Is there any evidence suggesting that ISB 1442 is likely to be safe for humans?

Research has shown that ISB 1442, a new treatment for multiple myeloma, is under careful study for safety. Early reports suggest patients generally tolerate this treatment well. Some studies have tested different doses to find the right balance between efficacy and side effects. During these tests, some side effects appeared, but they were manageable and expected for treatments of this kind.

ISB 1442 uses antibodies to target specific proteins on cancer cells, aiming to help the immune system fight cancer more effectively. Although the treatment is new and still under investigation, the evidence so far is promising for its safe use in humans. Ongoing studies will continue to provide more information about its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about ISB 1442 for multiple myeloma because it offers a new approach by using a subcutaneous injection, which is less invasive compared to standard intravenous treatments. Unlike typical therapies such as proteasome inhibitors, immunomodulators, and anti-CD38 therapies, ISB 1442 is designed for patients who have already undergone multiple lines of treatment and no longer respond to these options. The potential to administer ISB 1442 at escalating doses allows for personalized treatment plans, potentially improving outcomes for patients with relapsed or refractory multiple myeloma.

What evidence suggests that ISB 1442 might be an effective treatment for multiple myeloma?

Research shows that ISB 1442 is a promising new treatment for relapsed or refractory multiple myeloma (R/R MM). As a bispecific antibody, it targets two proteins, CD38 and CD47, on cancer cells. This dual action aims to enhance the immune system's ability to attack cancer cells. In lab studies, ISB 1442 slowed tumor growth more effectively than daratumumab, a current treatment, in mice. The treatment attached more easily to cells with high levels of CD38, suggesting it might be especially effective against certain tumors. Participants in this trial will receive ISB 1442, with some receiving it at the recommended Phase 2 Dose (RP2D) in the dose expansion phase, while others will participate in the dose escalation phase to determine optimal dosing. Although researchers are still collecting human data, early results are encouraging for those considering joining a trial. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with relapsed/refractory multiple myeloma who've tried at least three prior treatments, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 therapies. They should weigh at least 40 kg, have a life expectancy of more than 3 months, measurable disease by specific criteria, be able to perform daily activities (ECOG ≤2), and have proper organ function.

Inclusion Criteria

I weigh at least 40 kg and my multiple myeloma has worsened after standard treatment.

I have multiple myeloma and have tried at least 3 treatments without success.

My multiple myeloma has worsened after treatment, and tests show it's still active.

Exclusion Criteria

I haven't had major radiation therapy or to a large part of my bone marrow in the last 14 days.

I haven't had certain cancer treatments or investigational drugs recently.

Current participation in another interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) within 4 weeks of C1D1 and throughout the duration of this trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Phase 1: Dose Escalation

Participants with R/R multiple myeloma will be administered ISB 1442 weekly by subcutaneous injection in each 28-day cycle. Dose escalation will begin with an accelerated titration dose escalation and may convert to the standard (3 + 3) dose escalation.

Varies based on dose escalation

Phase 2: Dose Expansion

Participants will receive the recommended Phase 2 Dose (RP2D) of ISB 1442 SC injection determined in Phase 1 for treatment of R/R MM. Each treatment cycle duration is 28 days.

Varies based on number of cycles completed

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ISB 1442 SC injection at RP2D
• ISB 1442 SC injection escalating doses

Trial Overview The trial is testing ISB 1442 SC injection in two forms: escalating doses to find the right amount that's safe and effective (Phase 1) and then giving this dose to more patients to see how well it works (Phase 2). It's for people whose multiple myeloma has come back or didn't respond after standard treatment.

How Is the Trial Designed?

Group I: Phase 2 (Dose Expansion): R/R Multiple Myeloma Experimental Treatment 1 Intervention

This cohort includes the participants with pathologically confirmed R/R MM and must have received at least 3 prior lines of therapy, including proteasome inhibitors (PIs), immunomodulators (IMiDs), and anti CD38 therapies either in combination or as a single agent; and must not be candidates for regimens known to provide clinical benefit. Participants will receive the recommended Phase 2 Dose (RP2D) of ISB 1442 SC injection determined in Phase 1 of the study for treatment of R/R MM. Each treatment cycle duration is 28 days. The anticipated total duration for each participant will vary, depending on the number of cycles of treatment completed. The treatment phase will extend until participants experience disease progression or unacceptable toxicity, or until any other discontinuation criterion is met.

Group II: Phase 1: Dose escalation Experimental Treatment 1 Intervention

Participants with R/R multiple myeloma (MM) will be administered ISB 1442 weekly by subcutaneous (SC) injection in each 28-day cycle. Dose escalation will begin with an accelerated titration dose escalation and should certain conversion criteria be met, escalation will convert to the standard (3 + 3) dose escalation

Who Is Running the Clinical Trial?

Ichnos Sciences SA

Lead Sponsor

Trials

7

Recruited

750+

Published Research Related to This Trial

T-cell redirecting bispecific antibodies and CAR T cells are effective treatments for multiple myeloma but are associated with significant adverse events, including cytokine release syndrome and neurotoxicity.

The European Myeloma Network recommends specific management strategies for these adverse events, such as premedication, corticosteroids, and monitoring for symptoms, to improve patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network. Ludwig, H., Terpos, E., van de Donk, N., et al.[2023]

In the IFM2009-02 trial, patients with very advanced relapsed or refractory multiple myeloma who received pomalidomide and dexamethasone for more than one year showed a significantly higher overall response rate (83%) and median progression-free survival (20.7 months) compared to those treated for less than one year (43% response rate and 4.6 months PFS).

The study indicates that prolonged exposure to pomalidomide and dexamethasone can lead to improved survival outcomes in heavily treated patients, suggesting a potential shift in the treatment paradigm for multiple myeloma, although further research is needed to optimize this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe and prolonged survival with long-term exposure to pomalidomide in relapsed/refractory myeloma. Fouquet, G., Pegourie, B., Macro, M., et al.[2020]

In a study of 33 multiple myeloma patients with a history of allogeneic transplantation, CAR-T therapy showed a high overall response rate (ORR) of 92%, with 67% achieving complete response (CR) and 73% being minimal residual disease (MRD) negative.

Bispecific T-cell engagers (BsAb) also demonstrated efficacy, with an ORR of 44% and 44% MRD negative, but with a lower response rate compared to CAR-T; both therapies were associated with significant safety concerns, including high rates of cytokine release syndrome and infections, yet no exacerbation of graft-versus-host disease was noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor and bispecific T-cell engager therapies in multiple myeloma patients with prior allogeneic transplantation. Hammons, L., Haider, S., Portuguese, AJ., et al.[2023]

In a study of 93 newly diagnosed multiple myeloma patients treated with the VBCMP-M2 protocol, an overall response rate of 56% was observed, with 60% of stage II patients and 51% of stage III patients responding to treatment.

The median survival for all patients was 35 months, but the study found no significant advantage of the VBCMP-M2 combination therapy over other treatment regimens, including melphalan and prednisone alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The therapeutic efficacy of VBCMP-M2 protocol in multiple myeloma. Colović, MD., Janković, GM., Nikolov, VS., et al.[2015]

T-cell engaging bispecific antibodies (BsABs) show promise in treating multiple myeloma (MM) by redirecting T-cell activity to target malignant MM cells and immunosuppressive myeloid-derived suppressor cells (MDSC), potentially delaying disease progression.

Specific BsABs targeting antigens like BCMA and CD38 can effectively destroy MM cells and MDSC in the bone marrow microenvironment, suggesting a new therapeutic approach that could improve survival rates in MM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Targeting of Multiple Myeloma Stem Cells and Myeloid-Derived Suppressor Cells for Treatment of Chemotherapy-Resistant Multiple Myeloma. Uckun, FM.[2023]

In a study of 201 patients with multiple myeloma who underwent autogenetic peripheral blood stem cell transplantation (APBSCT) after induction therapy, achieving a complete response (CR) significantly improved both progression-free survival (PFS) and overall survival (OS), with median PFS of 32.93 months for CR patients compared to 18.13 months for those who did not achieve CR.

The study identified that the type of multiple myeloma (IgD vs. IgG) and the International Staging System (ISS) stage were important prognostic factors, with IgD type associated with worse outcomes and higher risk of disease progression, highlighting the need for tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and prognostic factors of induction therapy combined with autologous stem cell transplantation in 201 patients with multiple myeloma]. Jin, L., Fu, W., Xi, H., et al.[2020]

The combination of pomalidomide and dexamethasone is safe and shows significant efficacy in treating patients with advanced multiple myeloma, with an overall response rate of around 35% after multiple prior therapies.

In a study involving 84 patients, the median overall survival was 14.9 months, and the treatment was generally well-tolerated, with manageable side effects primarily related to myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: Intergroupe Francophone du Myélome 2009-02. Leleu, X., Attal, M., Arnulf, B., et al.[2022]

A pooled analysis of 1185 patients with relapsed/refractory multiple myeloma treated with bispecific antibodies (BsAbs) showed promising response rates, particularly with agents targeting B-cell maturation antigen (BCMA), although the median follow-up was short at 6.1 months.

Infectious complications were significant, with 50% of patients experiencing infections and 25.5% of deaths attributed to infections, highlighting the need for precautions to manage and treat infections in patients receiving BsAbs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of infections associated with the use of bispecific antibodies in multiple myeloma: a pooled analysis. Mazahreh, F., Mazahreh, L., Schinke, C., et al.[2023]

The combination of low-dose intravenous melphalan and bortezomib was found to be safe and effective for treating relapsed multiple myeloma, with an overall response rate of 68% and a maximum tolerated dose established at 7.5 mg/m² of melphalan.

Patients receiving the maximum tolerated dose showed even better results, with a 76% overall response rate and a median progression-free survival of 12 months, indicating that this treatment combination could significantly improve outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, low-dose intravenous melphalan, and dexamethasone for patients with relapsed multiple myeloma. Popat, R., Oakervee, H., Williams, C., et al.[2015]

In a phase I-II study involving 30 patients with previously treated multiple myeloma, the combination of interferon alfa-2b with melphalan and prednisone resulted in a 69% partial response rate, with a median response duration of over 11 months.

The study indicated that interferon alfa-2b does not interfere with the effectiveness of melphalan and prednisone, suggesting a potential additive or synergistic effect, warranting further investigation in randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon alfa-2b/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial. Cooper, MR., Fefer, A., Thompson, J., et al.[2019]

A systematic review of 13 studies involving 529 patients with relapsed refractory multiple myeloma (MM) showed that antibody-drug conjugates (ADCs) had an overall response rate (ORR) of 34-60% and complete response (CR) rates of 3-6%, indicating their potential effectiveness in treating this challenging condition.

Bispecific T-cell engagers demonstrated a higher ORR of 31-83% and CR rates of 7-22%, with manageable safety profiles, including common adverse events like cytokine release syndrome and neutropenia, suggesting they are promising options for patients with RRMM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dawn of a new era of antibody-drug conjugates and bispecific T-cell engagers for treatment of multiple myeloma: a systematic review of literature. Khattak, ZE., Hashmi, H., Khan, SI., et al.[2021]

In a study of 363 patients with untreated multiple myeloma, the combination of melphalan-prednisone and thalidomide (MPT) resulted in a significantly higher rate of very good partial responses (23%) compared to melphalan-prednisone and placebo (MP) (7%), indicating MPT has a strong antimyeloma effect.

Despite the improved response rates with MPT, there was no significant difference in overall survival between the two groups, with median survival times of 29 months for MPT and 32 months for MP, suggesting that while MPT is effective in reducing disease symptoms, it does not extend life expectancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Waage, A., Gimsing, P., Fayers, P., et al.[2021]

In a study of 23 patients with relapsed or refractory multiple myeloma, recombinant alpha-2 interferon (rIFNα2b) showed clinical activity, with about 25% of patients experiencing significant reductions in M-protein levels or improvements in bone pain after 12 weeks of treatment.

While the treatment was associated with flu-like symptoms and some patients experienced severe neutropenia, the lower dose of 5 × 10(6) IU/m² was well-tolerated, suggesting that rIFNα2b could be a viable option for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon in the Treatment of Refractory Multiple Myeloma: An Eastern Cooperative Oncology Group Study. Oken, MM., Kyle, RA., Kay, NE., et al.[2019]

In a study of 63 patients with multiple myeloma, those who received peripheral-blood stem-cell (PBSC) infusion had a faster recovery of blood cell counts compared to those who received only autologous bone marrow (BM) infusion.

The treatment resulted in a complete response in 40% of assessable patients, but 25% experienced treatment-related complications leading to death within 100 days, highlighting the need for improved treatment strategies and earlier interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose therapy followed by autologous hematopoietic stem-cell infusion for patients with multiple myeloma. Bensinger, WI., Rowley, SD., Demirer, T., et al.[2019]

Citations

1. nature.com nature.com/articles/s41467-024-46310-y

Development of ISB 1442, a CD38 and CD47 bispecific ... Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies.

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3364/533476/Dose-Escalation-of-ISB-1442-a-Novel-CD38

Dose Escalation of ISB 1442, a Novel CD38 Biparatopic x ... It combines two anti-CD38 binding arms with a single anti-CD47 arm to harness innate immunity and enhance tumor cell killing through multiple ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124061160

Dose Escalation of ISB 1442, a Novel CD38 Biparatopic x ... ISB 1442 is a fully human bispecific, biparatopic antibody targeting CD38 and CD47, generated using Ichnos' Bispecific Engagement by Antibodies based on the T ...

4. iginnovate.com iginnovate.com/2024/05/07/ichnos-glenmark-innovation-reports-the-publication-in-nature-communications-of-the-preclinical-development-of-isb-1442-bispecific-antibody-for-treatment-of-relapsed-refractory-multiple-myeloma/

ISB 1442 is currently being tested in a Phase I clinical trial in ... ISB 1442 consistently demonstrated superior tumor growth inhibition compared to daratumumab in preclinical mouse models in vivo and higher ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11784651/

Biparatopic binding of ISB 1442 to CD38 in trans enables ... Finally, the trans biparatopic binding by ISB 1442 enabled increased avidity to cells with higher CD38 surface densities, and thus improved ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05427812

NCT05427812 | Phase 1/2 Study of ISB 1442 in Relapsed/ ... This study is a first-in-human, Phase 1/2, open label study that will evaluate safety and efficacy of ISB 1442 in relapsed/refractory multiple myeloma (R/R MM).

7. multiplemyelomahub.com multiplemyelomahub.com/medical-information/u-s-fda-grants-orphan-drug-designation-to-isb-1442-for-the-treatment-of-rrmm

U.S. FDA grants orphan drug designation to ISB 1442 for ... An open-label, first-in-human, multicenter phase I/II study (NCT05427812) will assess the safety, tolerability, efficacy, pharmacokinetics, and ...