GTB-5550 in Advanced Solid Tumors

Summary

This is a first-in-human Phase 1a/1b trial of a B7-H3-targeted natural killer (NK) cell engager, referred to as a TriSpecific Killer Engager (TriKE), for the treatment of select solid tumor cancers. To be considered for the study, a patient must be 18 years or older, have histologically or cytologically confirmed advanced/metastatic cancer that, based on literature reports, expresses B7-H3 at a high frequency, measurable disease by RECIST 1.1 (exception: mCRPC limited to bone metastasis are exempt from this requirement), meets the disease specific criteria for prior failed therapy, and refractory to, intolerant of, or ineligible for therapy options that are known to provide clinical benefit for their diagnosis.

Eligibility

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.

Conditions4

Interventions1

Locations1 site

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