Title
Phase 1 trial with GD2-SADA:177Lu-DOTA Drug Complex in patients with recurrent or refractory metastatic solid tumors known to express GD2, including Small Cell Lung Cancer, High Risk Neuroblastoma, Sarcoma and Malignant Melanoma

Description
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

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.

Objective
Primary:
-Part A: To determine the optimal, safe GD2-SADA protein dose and dosing interval between
GD2-SADA and 177Lu-DOTA administrations
-Part B: To determine the maximum tolerable activity of 177Lu-DOTA
-Part C: To assess cumulative toxicity signals and safety profile following repeated dosing
and determine the recommended phase 2 dose (RP2D)

Secondary:
-To assess immunogenicity
-To assess anti-tumor activity
-To assess PFS and overall survival
-To assess dosimetry including tumor absorbed dose and whole body, selected organ absorbed
doses and blood dosimetry (Part A)
-To assess PK profile of GD2-SADA (Part A)
-To assess optimal dose of 177Lu-DOTA (Part B)

Treatment Experimental: GD2-SADA:177Lu-DOTA Complex
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
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
Other Name: two-step radioimmunotherapy

Key Eligibility 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
Patient willing and able to comply with the trial protocol

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

Applicable Disease Sites
Lung; Melanoma/Skin cancer; Sarcoma

Participating Institutions
UW Health University Hospital