Anti-CD38 A2 DAR T Cells for Multiple Myeloma

Recruiting at 2 trial locations

Overseen By Mike Royal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sorrento Therapeutics, Inc.

Disqualifiers: Brain metastasis, Spinal cord compression, HIV, 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: 28

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called STI-1492 (an Anti-CD38 A2 DAR T cell therapy) for individuals with multiple myeloma, a type of blood cancer, who have not responded to previous treatments. Researchers aim to determine the best dose by administering different amounts of STI-1492 to separate groups. Those whose multiple myeloma has returned or worsened after treatments and who exhibit specific signs of the disease might be suitable for this study. Participants must adhere to the study schedule and guidelines. 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.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic therapy for multiple myeloma at least 14 days before starting the study treatment. If you have received cellular therapy, it must be at least 8 weeks prior. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that STI-1492 is likely to be safe for humans?

Research shows that STI-1492 targets multiple myeloma cells by recognizing a protein called CD38. Early findings suggest that treatments using CAR T-cell therapy, which modifies a patient's immune cells to attack cancer cells, can be very effective. Since STI-1492 is just beginning human testing, information on its safety remains limited. Early trials typically focus on determining safe dosage levels and identifying any side effects.

While specific side effects of STI-1492 are not yet known, similar treatments have been studied for their tolerability. Participants might experience side effects common to cell therapies, such as flu-like symptoms or low blood cell counts. As trials progress, more information will clarify its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about STI-1492 for multiple myeloma because it uses a novel approach with Anti-CD38 A2 DAR T cells. Unlike standard treatments that typically involve chemotherapy or immunomodulatory drugs, STI-1492 is a type of cell therapy specifically engineered to target and destroy cancerous cells in a more precise way. This method not only promises to improve effectiveness by directly engaging the immune system against the cancer cells but also aims to minimize common side effects associated with traditional treatments. By harnessing the body's own immune cells, STI-1492 could potentially offer a more targeted and personalized treatment option for patients with multiple myeloma.

What evidence suggests that STI-1492 might be an effective treatment for multiple myeloma?

Research has shown that STI-1492, a new cell therapy under investigation in this trial, may help treat multiple myeloma, a type of blood cancer. This treatment uses specially modified T cells to specifically target and attack cancer cells. Early studies suggest that these modified cells can find and destroy cancer cells that other treatments might miss. Initial results highlight the potential of STI-1492 to assist patients whose cancer has returned or hasn't responded to standard treatments. Although these are early signs, the targeted approach of STI-1492 offers hope for better outcomes in challenging cases. ^{1 2 4 5 6}

Who Is on the Research Team?

Mike Royal, MD

Principal Investigator

Sorrento Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory multiple myeloma who've had previous treatments, can follow the study plan and contraception rules, have CD38 expression in their cancer cells, a life expectancy of at least 12 weeks, measurable disease levels, and good oxygen levels without assistance.

Inclusion Criteria

Your oxygen level when breathing normally is at least 92%.

My multiple myeloma has returned or didn't respond after treatment.

You are expected to live for at least 12 more weeks.

Exclusion Criteria

I have active plasma cell leukemia.

I have had cancer spread to my brain or spine.

My heart's pumping ability is below 40%.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive STI-1492 in a dose-escalation study to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)

28 days per cohort

Staggered intervals of at least 28 days between patients

Expansion Study

Participants receive STI-1492 at the determined RP2D to further assess safety and efficacy

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 54 months

What Are the Treatments Tested in This Trial?

Interventions

• STI-1492

Trial Overview The trial tests STI-1492, an experimental therapy involving anti-CD38 T cells. It's given once through the vein to see how safe it is and what dose works best for people whose multiple myeloma has come back or didn't respond to treatment.

How Is the Trial Designed?

Group I: STI-1492 Experimental Treatment 1 Intervention

Four dosing cohorts will be evaluated: Cohort 1 (1 × 10\^5 donor DAR-T cells/kg); Cohort 2 (5 × 10\^5 donor DAR-T cells/kg); Cohort 3 (1 × 10\^6 donor DAR-T cells/kg); Cohort 4 (3 × 10\^6 donor DAR-T cells/kg) where STI-1492 will be administered intravenously once.

STI-1492 is already approved in United States for the following indications:

Approved in United States as STI-1492 for:

• Relapsed or Refractory Multiple Myeloma

Who Is Running the Clinical Trial?

Sorrento Therapeutics, Inc.

Lead Sponsor

Trials

48

Recruited

2,000+

Published Research Related to This Trial

CD38 antibodies, like daratumumab and isatuximab, are effective in treating multiple myeloma by inducing cell death through immunomodulation and enhancing T-cell activity, particularly in patients who respond well to treatment.

Resistance to CD38-targeting therapies can arise from tumor-specific factors, such as reduced CD38 expression, and changes in the immune environment, but strategies exist to overcome these challenges by targeting other pathways involved in immune activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma. Bisht, K., Fukao, T., Chiron, M., et al.[2023]

AMG 424, a bispecific T-cell-recruiting antibody targeting CD38 and CD3, has shown promising efficacy in killing multiple myeloma cells and inducing T-cell proliferation while minimizing excessive cytokine release, which is crucial for reducing potential side effects.

In preclinical models, AMG 424 effectively inhibited tumor growth in mouse models of multiple myeloma and demonstrated B-cell depletion in cynomolgus monkeys, supporting its potential as a new therapeutic option for patients with this cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Multiple Myeloma with AMG 424, a Novel Anti-CD38/CD3 Bispecific T-cell-recruiting Antibody Optimized for Cytotoxicity and Cytokine Release. Zuch de Zafra, CL., Fajardo, F., Zhong, W., et al.[2020]

CD38 is a promising target for immunotherapy in Multiple Myeloma (MM) due to its high and uniform expression on myeloma cells, leading to the development of therapies like monoclonal antibodies (daratumumab and isatuximab).

Recent studies in pre-clinical models and clinical trials show that CD38-targeted immunotherapies, including radioimmunotherapy and CAR T-cell therapy, have potential efficacy in treating MM, although there are still limitations to consider.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD38: A Target for Immunotherapeutic Approaches in Multiple Myeloma. Morandi, F., Horenstein, AL., Costa, F., et al.[2020]

CD38-chimeric antigen receptor-transduced T cells showed strong anti-tumor effects against multiple myeloma and acute myeloid leukemia, effectively killing cancer cells in a dose-dependent manner, indicating their potential as a targeted cancer therapy.

While these engineered T cells can also attack some healthy CD38-positive cells, they do not prevent the growth of hematopoietic progenitor cells, and their activity can be controlled using a suicide gene, suggesting a safety mechanism for managing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Drent, E., Groen, RW., Noort, WA., et al.[2018]

The newly developed CD38-CAR-T cells, utilizing a nanobody targeting CD38, effectively proliferated and produced inflammatory cytokines, demonstrating strong potential for treating multiple myeloma by lysing CD38+ cancer cells.

In vivo studies showed that these CD38-CAR-T cells inhibited tumor growth in mice, indicating their efficacy as a promising therapeutic strategy for multiple myeloma with minimal off-target effects on healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Multiple Myeloma Activity of Nanobody-Based Anti-CD38 Chimeric Antigen Receptor T Cells. An, N., Hou, YN., Zhang, QX., et al.[2019]

The study presents a novel approach to creating CAR-NK cells that target CD38 in multiple myeloma by utilizing CD38dim NK cells, which are generated through long-term IL-2 stimulation, thus avoiding fratricide and enhancing cell viability.

The αCD38-CAR-NK cells demonstrated significant functionality against both CD38+ cell lines and primary multiple myeloma cells, indicating their potential as an effective immunotherapy for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges in αCD38-chimeric antigen receptor (CAR)-expressing natural killer (NK) cell-based immunotherapy in multiple myeloma: Harnessing the CD38dim phenotype of cytokine-stimulated NK cells as a strategy to prevent fratricide. Karvouni, M., Vidal-Manrique, M., Susek, KH., et al.[2023]

Affinity-optimized CD38CAR NK cells effectively target and eliminate multiple myeloma (MM) cells while sparing nonmalignant cells, demonstrating a strong safety profile.

These engineered NK cells showed significant anti-MM effects in preclinical models, including in patients who were resistant to existing therapies like daratumumab, highlighting their potential as a new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD38-specific Chimeric Antigen Receptor Expressing Natural Killer KHYG-1 Cells: A Proof of Concept for an "Off the Shelf" Therapy for Multiple Myeloma. Stikvoort, A., van der Schans, J., Sarkar, S., et al.[2021]

Researchers developed two new second-generation CAR-T cells that specifically target CD38, a protein commonly found on multiple myeloma cells, showing promising results in laboratory tests.

These CD38 CAR-T cells demonstrated effective activation and tumor-killing abilities, significantly outperforming untransduced T cells, and showed potential for rapid tumor elimination in live models, suggesting they could be a new treatment option for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the Therapeutic Effects of Novel Chimeric Antigen Receptor T Cells Targeting CD38 on Multiple Myeloma. Li, X., Feng, Y., Shang, F., et al.[2021]

This study found that myeloma plasma cells, specifically CD38(bright,++) and CD38(dim,+) cells from eight multiple myeloma patients, can function as antigen-presenting cells, stimulating T-cell responses.

The plasma cells expressed various surface markers and could present antigens, leading to T-cell proliferation and IFN-gamma secretion, indicating a potential role in immune responses despite their cancerous nature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myeloma bone marrow plasma cells: evidence for their capacity as antigen-presenting cells. Yi, Q., Dabadghao, S., Osterborg, A., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05007418

NCT05007418 | Study to Assess Allogeneic Anti-CD38 A2 ... Study to Assess Allogeneic Anti-CD38 A2 Dimeric Antigen Receptor T Cells in Relapsed or Refractory Multiple Myeloma. ClinicalTrials.gov ID NCT05007418. Sponsor ...

2. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/allogeneic-anti-cd38-dar-t-cells-sti-1492

Clinical Trials Using Allogeneic Anti-CD38 DAR-T Cells ... Review the clinical trials studying allogeneic anti-cd38 dar-t cells sti-1492 on this list and use the filters to refine the results by age and location.

3. withpower.com withpower.com/trial/phase-1-multiple-myeloma-10-2021-336c4

Anti-CD38 A2 DAR T Cells for Multiple Myeloma This trial tests a new drug called STI-1492 for patients whose multiple myeloma has returned or not responded to other treatments. The drug is given through ...

4. adisinsight.springer.com adisinsight.springer.com/drugs/800055148

STI 1492 - AdisInsight - Springer Anti-CD38 dimeric antigen receptor T (DAR-T) cell is an allogenic, off-the-shelf therapy being developed by Sorrento Therapeutics for the treatment of.

5. aceatherapeutics.com aceatherapeutics.com/pipeline/sti-1492/

STI-1492 - Anti-CD38 A2 KOKI DAR-T cells - ACEA STI-1492, a drug “Anti-CD38 A2 KOKI DAR-T cells”, contains the healthy donor derived T cells that have been genetically engineered by non-viral gene editing ...

6. synapse.patsnap.com synapse.patsnap.com/drug/fa56bdbd3b80488dbb92236a388120e3

STI-1492 - Drug Targets, Indications, Patents Abstract: Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma targeting B-cell maturation antigen (BCMA) induces high overall response rates.