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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new radioimmunotherapy treatment for individuals with non-Hodgkin lymphoma, a cancer affecting the lymphatic system. The treatment combines CD38-SADA and 177Lu-DOTA to determine the optimal and safest dose. It targets those whose cancer has returned or does not respond to standard treatments. Participants must have a type of lymphoma visible on special scans and a specific protein, CD38, in their tumor. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Researchers are conducting studies to understand the safety of the CD38-SADA:177Lu-DOTA treatment in humans. This treatment uses a two-step process called radioimmunotherapy, which employs radioactive substances to target cancer cells.

As this is an early-stage study, detailed safety information is not yet available. The main goal is to find doses that are both safe and effective. Early-stage trials closely monitor any side effects and determine the best dosage. Patient safety remains a top priority, and researchers will record and address any side effects quickly.

Since this is a new treatment for non-Hodgkin lymphoma, researchers are still learning about its safety. Participants will be closely monitored to ensure their well-being throughout the trial. ^{1 2 3 4 5}

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

Unlike the standard treatments for lymphoma, which often include chemotherapy and monoclonal antibodies, the CD38-SADA:177Lu-DOTA Complex offers a novel approach by using a targeted radioligand therapy. This treatment is unique because it directly delivers a radioactive payload to the lymphoma cells by targeting the CD38 protein, potentially reducing damage to healthy cells and minimizing side effects. Researchers are excited about this treatment as it combines precision targeting with the powerful effects of radiation, which could lead to more effective and less toxic treatment options for patients with lymphoma.

What evidence suggests that the CD38-SADA:177Lu-DOTA Complex might be an effective treatment for non-Hodgkin Lymphoma?

Research has shown that the treatment called CD38-SADA:177Lu-DOTA complex, which participants in this trial will receive, demonstrated strong effects against tumors in early studies. These studies found that this treatment effectively targets tumors with the CD38 protein, present in some lymphoma cells. The treatment reaches the tumor quickly, achieving its highest concentration within 12 hours, indicating swift targeting of cancer cells. This suggests that this type of radioimmunotherapy might effectively treat non-Hodgkin lymphoma by delivering radiation directly to the cancer cells. While more research is needed to confirm these findings in humans, the early results are promising. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4434.1/529173/CD38-SADA-Pretargeted-Radioimmunotherapy-PRIT-with

CD38-SADA Pretargeted Radioimmunotherapy (PRIT) with ... ... SADA PRIT with Lu177-DOTA has demonstrated robust anti-tumor efficacy. ... Efficacy and Safety Results of a Phase 1 Study of 177 lu-DOTA-HH1 ...

2. withpower.com withpower.com/trial/phase-1-lymphoma-1-2024-889ac

CD38-SADA:177Lu-DOTA Complex for Lymphoma 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 ...

3. biospace.com biospace.com/press-releases/y-mabs-announces-first-patient-dosed-in-phase-1-clinical-trial-evaluating-cd38-sada-pre-targeted-radioimmunotherapy-in-relapsed-refractory-non-hodgkin-lymphoma

Y-mAbs Announces First Patient Dosed in Phase 1 Clinical ... CD38-SADA PRIT with 177Lu-DOTA has demonstrated robust anti-tumor efficacy in preclinical studies and is currently being investigated in adults ...

4. synapse.patsnap.com synapse.patsnap.com/drug/8ae612789a024106a8ef3982a73f4e3c

CD38-SADA:177Lu-DOTA Complex - Drug Targets, ... Patients will receive up to three cycles of therapy. The primary study outcome will evaluate safety and initial signals of efficacy using repeated dosing. Y- ...

5. ir.ymabs.com ir.ymabs.com/news-releases/news-release-details/y-mabs-therapeutics-announces-us-fda-clearance-investigational

Y-mAbs Therapeutics Announces U.S. FDA Clearance of ... This trial will have two parts: Part A, CD38-SADA dose escalation with fixed 177Lu-DOTA payload doses to explore optimal CD38-SADA protein dose ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05994157/phase-1-open-label-dose-escalation-trial-with-cd38-sada177-lu-dota-drug-complex-in-subjects-with-relapsed-or-refractory-non-hodgkin-lymphoma

Phase 1, Open-label, Dose-escalation Trial with CD38 ... Patients with non-Hodgkin Lymphoma will be treated with CD38-SADA:177Lu-DOTA complex (The IMP is a two-step radioimmunotherapy, delivered as ...

7. ir.ymabs.com ir.ymabs.com/news-releases/news-release-details/y-mabs-announces-first-patient-dosed-phase-1-clinical-trial

Y-mAbs Announces First Patient Dosed in Phase 1 Clinical ... CD38-SADA is a bispecific fusion protein that tightly binds to the CD38 glycoprotein and to 177Lu-tetraxetan (177Lu -DOTA), a “caged” ...

8. clin.larvol.com clin.larvol.com/trial-detail/NCT05994157

Phase 1, Open-label, Dose-escalation Trial with CD38 ... This Phase 1 trial (Trial 1201) is a dose-escalation, open-label, single-arm, multi-center trial investigating the safety and tolerability of the CD38-SADA: ...

9. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07735

Phase 1, Open-label, Dose-escalation Trial with CD38 ... 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 ...