CD38-SADA:177Lu-DOTA Complex for Lymphoma

Recruiting at 6 trial locations

Overseen By Joris Wilms

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Y-mAbs Therapeutics

Must not be taking: Chemotherapy, Immunotherapy, CAR-T, others

Disqualifiers: CNS lymphoma, Bone marrow involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

30 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had systemic chemotherapy, radiotherapy, immunotherapy, or major surgery within 3 weeks before starting the trial treatment.

What data supports the effectiveness of the CD38-SADA:177Lu-DOTA Complex treatment for lymphoma?

Research shows that targeting CD38, a marker found on some lymphoma cells, with a similar treatment using a CD38-targeting antibody labeled with a radioactive substance (Lu-177) can effectively suppress tumor growth in preclinical models. This suggests that the CD38-SADA:177Lu-DOTA Complex might also be effective in treating lymphoma by targeting the same marker. ^{1 2 3 4 5}

What makes the CD38-SADA:177Lu-DOTA Complex treatment unique for lymphoma?

The CD38-SADA:177Lu-DOTA Complex is unique because it targets the CD38 protein on lymphoma cells, using a radioactive component (177Lu) to deliver targeted radiation therapy, potentially offering a more precise treatment compared to traditional chemotherapy or radiotherapy. ^{1 2 3 4 6}

What is the purpose of this trial?

Patients with non-Hodgkin Lymphoma will be treated with CD38-SADA:177Lu-DOTA complex (The IMP is a two-step radioimmunotherapy, delivered as two separate products CD38-SADA and 177Lu-DOTA) to establish optimal and safe therapeutic doses and dosing schedule of CD38-SADA, and 177Lu-DOTA.

Eligibility Criteria

This trial is for adults with Non-Hodgkin Lymphoma that's come back or hasn't responded to treatment, and who have no other standard options left. They must understand the study and agree to participate, have a type of lymphoma visible on certain scans, CD38 positive tumors, and be able to do some daily activities without significant help.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

My lymphoma is active and can be measured.

Each subject must sign an ICF indicating that he or she understands the purpose of, and procedures required for the trial and is willing to participate in the trial.

Exclusion Criteria

I haven't had chemotherapy, radiotherapy, immunotherapy, or major surgery in the last 3 weeks.

Over 40% of my bone marrow is affected by lymphoma.

I have not had radioimmunotherapy in the last 100 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive CD38-SADA:177Lu-DOTA complex to establish optimal and safe therapeutic doses and dosing schedule

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CD38-SADA:177Lu-DOTA Complex

Trial Overview The trial tests a two-step radioimmunotherapy called CD38-SADA:177Lu-DOTA Complex in patients with relapsed or refractory Non-Hodgkin Lymphoma. It aims to find the safest and most effective doses and schedule for this new therapy.

Participant Groups

Group I: CD38-SADA:177Lu-DOTA Complex Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Y-mAbs Therapeutics

Lead Sponsor

Trials

26

Recruited

1,600+

Findings from Research

CD38 is identified as a specific biomarker for lymphoma, which can help differentiate between various lymphoma subtypes, particularly aggressive ones like Burkitt's lymphoma and diffuse large B cell lymphoma.

The study demonstrates that a CD38-targeting monoclonal antibody, daratumumab, can be effectively used for both imaging and treatment of lymphoma, with Zr-89 for PET imaging and Lu-177 for tumor suppression, showing promise for improved patient management in preclinical models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD38-Targeted Theranostics of Lymphoma with 89Zr/177Lu-Labeled Daratumumab. Kang, L., Li, C., Rosenkrans, ZT., et al.[2022]

The study developed a 64Cu-labeled Dara-F(ab')2, which demonstrated rapid and high tumor uptake in CD38-positive lymphoma models, peaking at 12 hours, compared to the slower uptake of the full antibody, daratumumab, which peaked at 48 hours.

This new imaging agent showed significantly lower uptake in blood, bone, and muscle, resulting in better tumor-to-background ratios, indicating its potential for improved PET imaging in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

64Cu-labeled daratumumab F(ab')2 fragment enables early visualization of CD38-positive lymphoma. Kang, L., Li, C., Yang, Q., et al.[2023]

Daratumumab, an anti-CD38 monoclonal antibody, was found to be significantly more effective than rituximab in suppressing the growth of CD20-negative, CD38-positive diffuse large B-cell lymphoma (DLBCL) tumors in a patient-derived xenograft model.

The study suggests that daratumumab could be a promising treatment option for patients with relapsed DLBCL who are CD20-negative, potentially in combination with salvage chemotherapy, and may also be useful for developing targeted therapies like antibody-drug conjugates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD38 Therapy with Daratumumab for Relapsed/Refractory CD20-Negative Diffuse Large B-Cell Lymphoma. Vockova, P., Svaton, M., Karolova, J., et al.[2022]

177Lu-DOTA-HH1 (177Lu-HH1) demonstrated significant tumor growth delay and increased survival in mice with non-Hodgkin lymphoma compared to other treatments, indicating its efficacy as a targeted therapy.

The treatment was well-tolerated at a dose of 530 MBq/kg, while 177Lu-DOTA-rituximab caused severe radiation toxicity in some mice, likely due to its longer retention in organs and slower internalization compared to 177Lu-HH1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma. Repetto-Llamazares, AH., Larsen, RH., Patzke, S., et al.[2018]

Rituximab was successfully conjugated with p-SCN-Bn-DOTA and radiolabeled with [90]Y, achieving a high radiochemical purity of over 98%, indicating its potential as a stable radioimmunotherapeutic agent for non-Hodgkin's lymphoma.

In vitro studies demonstrated that the [90]Y-DOTA-rituximab conjugate specifically binds to CD20-expressing Raji cells, suggesting its effectiveness in targeting cancer cells while showing low activity in non-target tissues, which supports its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation & in vitro evaluation of ⁹⁰Y-DOTA-rituximab. Kameswaran, M., Pandey, U., Dash, A., et al.[2018]

CD38 is a promising target for anticancer therapy, particularly in treating multiple myeloma and immunoglobulin light-chain amyloidosis, with several anti-CD38 antibodies like daratumumab and isatuximab already approved by the FDA.

Beyond cancer, CD38 is implicated in various diseases, including autoimmune disorders and viral infections, suggesting its potential as a therapeutic target and biomarker in conditions like transplant rejection and systemic lupus erythematosus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD38 in Neoplasms and Non-Cancer Diseases. Szlasa, W., Czarny, J., Sauer, N., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

CD38-Targeted Theranostics of Lymphoma with 89Zr/177Lu-Labeled Daratumumab. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

64Cu-labeled daratumumab F(ab')2 fragment enables early visualization of CD38-positive lymphoma. [2023]

3. Czech Republic pubmed.ncbi.nlm.nih.gov

Anti-CD38 Therapy with Daratumumab for Relapsed/Refractory CD20-Negative Diffuse Large B-Cell Lymphoma. [2022]

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

Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma. [2018]

5. India pubmed.ncbi.nlm.nih.gov

Preparation & in vitro evaluation of ⁹⁰Y-DOTA-rituximab. [2018]

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

Targeting CD38 in Neoplasms and Non-Cancer Diseases. [2022]