GTB-5550 in Advanced Solid Tumors

Inclusion criteria

• Measurable disease per RECIST 1.1. (Exception: mCRPC limited to bone metastasis is exempt from this requirement).
• Age 18 years or older at the time of consent, ECOG Performance Status 0 to 2
• Acute effects of any prior therapy must have resolved to baseline or Grade ≤ 1 NCI CTCAE v5 except for AEs not constituting a safety risk in the opinion of the enrolling Investigator.
• Adequate organ function within 14 days (30 days for cardiac) of Cycle 1 Day 1 defined as:
• Hematologic: hemoglobin ≥ 9 g/dL (may be transfused not more than 2 units of pRBCs within 7 days prior to Cycle 1 Day 1 to meet this requirement); absolute neutrophil count (ANC) ≥ 1500/ul (granulocyte colonystimulating factor (s) is not allowed to achieve ANC threshold or within 7 days of Cycle 1 Day 1); platelets ≥ 100 x 10\^9/L (may be transfused not more than 2 units of platelets within 7 days prior to Cycle 1 Day 1 to meet this requirement); absolute lymphocyte count (ALC) ≥ 300/ul.
• Albumin ≥ 3.0 g/dL.
• Renal: a patient BSA corrected glomerular filtration rate ≥ 45 mL/min as calculated using the Modified Cockroft-Gault equation (Rostoker et al. 2007).
• Hepatic: AST and ALT ≤1.5 x upper limit of normal (ULN) and total bilirubin ≤1.5 x ULN.
• Cardiac: New York Heart Association (NYHA) Class I or II ; left ventricular ejection fraction (LVEF) ≥ 45% by echocardiogram, MUGA, or cardiac MRI.
• Adequate pulmonary function with PFTs \> 50% FEV1 if symptomatic or known impairment.
• Sexually active couples of childbearing-potential must agree to use effective contraception or abstinence during treatment and for at least 4 months after the final dose of GTB-5550.
• Agrees to stay within a 60-minute drive of the study center through the Cycle 1 Day 15 visit for the Phase 1a study only.
• Provides voluntary written consent prior to the performance of any research related activity

Exclusion criteria

• Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days prior to the 1st dose of GTB-5550. Radioligand therapy requires at least 1 cycle washout (6 weeks for Pluvicto, 4 weeks for Xofigo).
• Prior organ allograft or allogeneic transplantation. An exception is made for FA patients with prior history of allogeneic hematopoietic stem cell transplant off immune suppressive therapy for \> 1 year.
• Pregnant or breastfeeding or planning pregnancy within 4 months after the last dose of GTB-5550.
• The potential risk of QT/QTc prolongation is unknown in humans receiving GTB-5550; therefore, either of the following is an exclusion criteria: QTc interval \> 480 msec at screening and/or a family history of long QT syndrome.
• Prior malignancy other than the one under treatment except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer which is currently in complete remission, or any other cancer from which the patient has been disease-free for 1 year after surgical or other definitive treatment.
• Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 1 year or any other diseases requiring immunosuppressive therapy while on study. Inhaled or topical steroids, and adrenal replacement steroid doses ≤10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Active systemic infection requiring parenteral antibiotic therapy. Any prior systemic infections must have resolved to Grade 1 or lower following optimal therapy.
• Psychiatric illness/social situations that in the judgement of the enrolling investigator would limit compliance with study requirements.
• Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient's participation.