GD2-SADA:177Lu-DOTA Complex in Patients With Solid Tumors Known to Express GD2

Study Overview
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Brief Summary
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Patients with Small Cell Lung Cancer, Sarcoma and Malignant Melanoma will be treated with GD2-SADA:177Lu-DOTA complex(The IMP is a two-step radioimmunotherapy, delivered as two separate products GD2-SADA and 177Lu-DOTA) to assess safety and tolerability

Detailed Description
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A phase 1 dose-escalation single-arm, open-label, non-randomized, multi-center trial of the safety and tolerability of GD2-SADA:177Lu-DOTA complex in GD2 expressing solid tumors. The trial is planned as a Phase 1 trial with three parts, A, B and C. Escalation in this trial will be based on a classical 3+3 trial design. Part A is a GD2-SADA dose escalation phase, in which patients will receive one treatment cycle. Part B is a 177Lu-DOTA dose escalation phase, in which patients will receive up to 2 treatment cycles . Part C is a repeated dosing phase where the doses determined in Part A and B will be administered. Patients will receive repeated treatment cycles with a maximum of 5 cycles.

Official Title
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Phase 1 Trial With GD2-SADA:177Lu-DOTA Complex in Patients With Recurrent or Refractory Metastatic Solid Tumors Known to Express GD2, Including Small Cell Lung Cancer, Sarcoma and Malignant Melanoma

Conditions
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SCLC, Malignant Melanoma, Sarcoma

Intervention / Treatment
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* Drug: GD2-SADA:177Lu-DOTA Complex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Age ≥18 years at the time of informed consent, for sarcoma age ≥16 years of age at time of informed consent/assent Measurable disease according to RECIST 1.1 ECOG performance status 0-1 Expected survival >3 months Platelet counts ≥100,000 cells/mm3 Hemoglobin ≥9 g/dL Adequate renal function with serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60mL/min as calculated using the Cockcroft-Gault equation Patient willing and able to comply with the trial protocol Exclusion Criteria: Systemic chemotherapy, radiotherapy, immunotherapy, or major surgery administered within 3 weeks prior to the first planned dosing of the IMP per protocol Patients receiving any other investigational therapy for their cancer within 3 weeks prior to the first planned dosing of the IMP per protocol Ongoing radiation toxicities from prior RT therapy Patients with a diagnosis of autoimmune diseases or immunodeficiencies or documented infection with human immunodeficiency virus (HIV) or hepatitis B or C virus (active) Prior treatment with anti-GD2 antibody

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 1 dose-escalation single-arm, open-label, non-randomized, multi-center trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GD2-SADA:177Lu-DOTA Complex<br>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 | Drug: GD2-SADA:177Lu-DOTA Complex<br>* The IMP is a two-step radioimmunotherapy, delivered as two separate products GD2-SADA and 177Lu-DOTA, both will be administered as an IV infusion<br>* Other names: two-step radioimmunotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the optimal, safe GD2-SADA protein dose and dosing interval between GD2-SADA and 177Lu-DOTA administrations | Occurrence of DLTs (Part A) | 6 weeks | 
| To determine maximum tolerable activity of 177Lu-DOTA | Occurrence of DLTs (Part B) | 6 weeks | 
| To assess cumulative toxicity signals and safety profile (Number and severity of adverse events) following repeated dosing and determine the recommended phase 2 dose (RP2D) | Number and severity of adverse events (Part C) | 52 weeks |