GD2-SADA:177Lu-DOTA Complex for Small Cell Lung Cancer

Recruiting at 7 trial locations

Overseen By Joris Wilms

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Y-mAbs Therapeutics

Must not be taking: Investigational therapies

Disqualifiers: Autoimmune diseases, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for certain types of cancer, including small cell lung cancer, high-risk neuroblastoma, sarcoma, and malignant melanoma. The treatment, GD2-SADA:177Lu-DOTA Complex, involves two steps of radioimmunotherapy, which uses radioactive substances alongside the immune system to target cancer cells. The main goal is to assess the safety and tolerability of this treatment for patients. Individuals living with one of these cancers who haven't recently undergone intensive treatments might be suitable for this trial. 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 chemotherapy, radiotherapy, immunotherapy, or major surgery at least 3 weeks before starting the study treatment. It does not specify about other medications, so you should discuss your current medications with the trial team.

Is there any evidence suggesting that GD2-SADA:177Lu-DOTA Complex is likely to be safe for humans?

Research has shown that GD2-SADA:177Lu-DOTA, a new treatment, is undergoing early trials to assess its safety and tolerability. Researchers aim to determine the right dosage and monitor for side effects. As a Phase 1 trial, this marks one of the first instances of testing this treatment in humans.

In these early studies, scientists primarily focus on the body's response to the treatment and any adverse effects. While safety data remains limited, the trial is designed to closely monitor patient reactions. Since the treatment is not yet approved for other conditions, no existing safety data can be inferred.

In summary, GD2-SADA:177Lu-DOTA is in the early testing stages, with limited safety information available. Participants should understand that the trial aims to evaluate how well individuals tolerate the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for small cell lung cancer, such as chemotherapy and immunotherapy, focus on killing cancer cells or boosting the immune response. But the GD2-SADA:177Lu-DOTA Complex works differently, targeting cancer cells with a two-step radioimmunotherapy approach. This treatment combines a targeting molecule, GD2-SADA, with a radioactive compound, 177Lu-DOTA, to deliver radiation directly to cancer cells, potentially reducing damage to healthy tissue. Researchers are excited about this method because it promises a more precise attack on cancer cells, which could lead to better outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that GD2-SADA:177Lu-DOTA Complex might be an effective treatment for small cell lung cancer?

Research has shown that the GD2-SADA:177Lu-DOTA complex, the treatment under study in this trial, is a promising new option for certain GD2-positive cancers. Other studies using similar radioactive compounds, such as 177Lu-DOTATATE, have demonstrated that patients can live longer without disease progression. Specifically, these studies reported that patients with advanced lung neuroendocrine tumors lived for a median of 23 months without their cancer worsening. The GD2-SADA:177Lu-DOTA complex targets cancer cells and delivers radiation directly to them, potentially killing the cancer more effectively while sparing healthy cells. Early findings suggest that this two-step treatment could offer hope for individuals with hard-to-treat cancers like small cell lung cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

Taofeek K Owonikoko, MD/PhD

Principal Investigator

University of Maryland, Marlene & Steward Greenebaum Comprehensive Cancer Center 22 S Greene St, Baltimore, MD 21201

Are You a Good Fit for This Trial?

This trial is for adults with Small Cell Lung Cancer, Sarcoma, or Malignant Melanoma. Participants must have a life expectancy over 3 months, certain blood cell counts within range, measurable disease by RECIST 1.1 standards, and good performance status. They should not have had recent cancer treatments or suffer from autoimmune diseases.

Inclusion Criteria

You are expected to live for more than 3 months.

My kidney function is good based on my creatinine levels.

Signed informed consent from patient, legal guardian(s) and/or adolescents obtained in accordance with local regulations. Pediatric patients must provide assent as required by local regulations.

Exclusion Criteria

I have been treated with anti-GD2 antibody before.

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

I have an autoimmune disease, immunodeficiency, or an active infection with HIV or hepatitis B/C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

GD2-SADA Dose Escalation

Part A: GD2-SADA dose escalation phase, patients receive one treatment cycle

6 weeks

177Lu-DOTA Dose Escalation

Part B: 177Lu-DOTA dose escalation phase, patients receive up to 2 treatment cycles

6 weeks

Repeated Dosing

Part C: Repeated dosing phase with doses determined in Part A and B, up to 5 cycles

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GD2-SADA:177Lu-DOTA Complex

Trial Overview The trial tests GD2-SADA:177Lu-DOTA Complex on patients to evaluate its safety and how well they tolerate it. It's a two-step radioimmunotherapy involving separate administrations of GD2-SADA and 177Lu-DOTA.

How Is the Trial Designed?

Group I: GD2-SADA:177Lu-DOTA Complex Experimental Treatment 1 Intervention

GD2-SADA IV. infusion followed by 177Lu-DOTA IV. infusion (The IMP is a two-step radioimmunotherapy, delivered as two separate products GD2-SADA and 177Lu-DOTA ). 1 treatment cycle in Part A, 2 treatment cycles in Part B and up to 5 treatment cycles in Part C

Who Is Running the Clinical Trial?

Y-mAbs Therapeutics

Lead Sponsor

Trials

26

Recruited

1,600+

Published Research Related to This Trial

The targeted alpha-particle therapy [225Ac]Ac-DOTA-TATE showed promising efficacy in delaying tumor growth in small animal models of lung neuroendocrine neoplasms, indicating its potential for treating patients who are resistant to standard therapies like [177Lu]Lu-DOTA-TATE.

In toxicity studies, [225Ac]Ac-DOTA-TATE demonstrated a high safety profile with no significant adverse effects in most animals, although higher doses led to chronic nephropathy, highlighting the need for careful dosing in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of [225Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms. Tafreshi, NK., Pandya, DN., Tichacek, CJ., et al.[2022]

In a study of 48 patients with advanced progressive lung neuroendocrine tumors, treatment with 177Lu-DOTATATE showed a median progression-free survival of 23 months and an overall survival of 59 months, indicating its efficacy in managing these tumors.

The treatment was found to be safe, with most adverse events being reversible; the most common severe side effect was lymphopenia, occurring in 14% of patients, and there were no cases of myelodysplasia or leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of 177Lu-DOTATATE in Lung Neuroendocrine Tumors: A Bicenter study. Zidan, L., Iravani, A., Oleinikov, K., et al.[2022]

In a study of 71 patients aged 70 and older with advanced neuroendocrine tumors treated with 177Lu-DOTATATE, the treatment showed a median progression-free survival of 36 months and overall survival of 47 months, indicating its efficacy in this age group.

The treatment was well-tolerated, with only 2.8% experiencing significant myelosuppression, and there was no decline in health-related quality of life, suggesting that 177Lu-DOTATATE is a safe option for older patients with advanced NET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-DOTATATE in older patients with metastatic neuroendocrine tumours: safety, efficacy and health-related quality of life. Chen, L., Navalkissoor, S., Quigley, AM., et al.[2021]

The co-infusion of amino acids (AA) during treatment with 177Lu-Dotatate significantly affects its pharmacokinetics, increasing the elimination rate constant by an average of 1.5-fold, which helps reduce potential nephrotoxicity.

However, this effect varies greatly among individuals, leading to high inter-individual variability in drug exposure and associated hematological toxicity, such as lymphopenia, indicating the need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Interaction of Amino Acid Infusion on 177Lu-Dotatate Pharmacokinetics in Patients with Gastroenteropancreatic Neuroendocrine Tumors. Puszkiel, A., Bauriaud-Mallet, M., Bourgeois, R., et al.[2020]

Salvage treatment with [177Lu-DOTA,Tyr3]octreotate is effective and safe for patients with progressive bronchial neuroendocrine tumors (NET) or gastroenteropancreatic NET (GEP-NET), showing a median overall survival of 80.8 months after initial treatment.

The treatment resulted in low rates of severe side effects, with only 6.6% and 7.7% of patients experiencing grade III/IV bone marrow toxicity after re-treatment and re-re-treatment, respectively, and no cases of severe kidney toxicity were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage peptide receptor radionuclide therapy with [177Lu-DOTA,Tyr3]octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumours. van der Zwan, WA., Brabander, T., Kam, BLR., et al.[2020]

[177Lu]Lu-DOTA-TATE shows promising antitumor activity in treating advanced somatostatin receptor-positive tumors, including pheochromocytoma/paraganglioma and bronchial neuroendocrine tumors, based on a systematic review of 16 studies.

The treatment is generally safe, with most side effects being mild to moderate and transient, similar to those observed in patients with gastroenteropancreatic neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review. Hertelendi, M., Belguenani, O., Cherfi, A., et al.[2023]

Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE has shown a 39% objective response rate and a 43% rate of stable disease in over 1,200 patients with neuroendocrine tumors, indicating its efficacy in treating these slow-growing tumors.

The therapy is considered safe, with only a small percentage of patients experiencing long-term toxicities, such as acute leukemia (0.7%) and myelodysplastic syndrome (1.5%), while no significant renal or hepatic failures were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors. Brabander, T., van der Zwan, WA., Teunissen, JJM., et al.[2022]

The study successfully converted a gallium-68 imaging agent into a lutetium-177 therapeutic agent for prostate cancer, demonstrating strong PSMA binding affinity comparable to the FDA-approved [177Lu]Lu-PSMA-617.

Biodistribution studies in mice showed that the new agent [177Lu]Lu-7 had a longer blood half-life and higher tumor uptake than both [177Lu]Lu-4 and [177Lu]Lu-PSMA-617, indicating its potential for improved therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177). Zha, Z., Choi, SR., Li, L., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS3162

Phase 1 trial of GD2-SADA:177Lu-DOTA drug complex in ... A first-in-human, dose-escalation, single-arm, open-label, non-randomized, multicenter phase 1 trial with the purpose of evaluating safety and tolerability of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05130255

Study Details | NCT05130255 | GD2-SADA:177Lu-DOTA ... Study Overview. Brief Summary. Patients with Small Cell Lung Cancer, High Risk Neuroblastoma, Sarcoma and Malignant Melanoma will be treated with GD2 ...

3. ir.ymabs.com ir.ymabs.com/news-releases/news-release-details/y-mabs-announces-presentation-gd2-sada-study-asco

Y-mAbs Announces Presentation of GD2-SADA Study at ASCO Theranostic Platform for the treatment of certain GD2-positive solid tumors, including small cell lung cancer, sarcoma and malignant melanoma will be presented ...

4. withpower.com withpower.com/trial/phase-1-melanoma-4-2022-01568

GD2-SADA:177Lu-DOTA Complex for Small Cell Lung ... In a study of 48 patients with advanced progressive lung neuroendocrine tumors, treatment with 177Lu-DOTATATE showed a median progression-free survival of 23 ...

5. mskcc.org mskcc.org/cancer-care/clinical-trials/23-029

A Phase 1 Study of GD2-SADA:177Lu-DOTA in People ... The purpose of this study is to find the best doses and dosing schedules for the investigational drugs GD2-SADA and 177Lu-DOTA when given together in people ...

6. ir.ymabs.com ir.ymabs.com/news-releases/news-release-details/y-mabs-presents-gd2-sada-prit-trial-progress-poster-advances

Y-mAbs Presents GD2-SADA PRIT Trial in Progress Poster at ... The trial in progress poster titled “A phase 1 trial of pretargeted radioimmunotherapy with GD2-SADA: 177 Lu-DOTA in patients with high-risk neuroblastoma and ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT05130255

GD2-SADA:177Lu-DOTA Complex in Patients With Solid ... The Phase 1 dose-escalation, single-arm, open-label, non-randomized, multicenter trial (NCT05130255) targets malignant melanoma, sarcoma and small cell lung ...