GTB-5550 treatment for people with advanced solid tumors.

MT2025-14: A Phase 1a/1b Study of GTB-5550, a Camelid Nanobody TriSpecific Killer Engager (camB7-H3 TriKE®), in Select Advanced Solid Tumors That Failed Prior Therapy

This Phase 1 trial tests GTB-5550, a B7-H3-targeting natural killer (NK) cell engager, in adults with advanced solid tumors who have exhausted or are ineligible for standard treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 175 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Masonic Cancer Center, University of Minnesota (other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, radiation
• Locations: 1 site (Minneapolis, Minnesota)
• Trial ID: NCT07541573 on ClinicalTrials.gov

What this trial studies

This first-in-human Phase 1a/1b trial is testing GTB-5550, a tri-specific killer engager (TriKE) that links an anti-CD16 arm, wildtype IL-15, and an anti-B7-H3 arm to activate and expand NK cells against cancer. The study begins with a dose-escalation Phase 1a to identify a safe dose and then proceeds to Phase 1b expansion cohorts in selected tumor types including castration-resistant prostate, breast, pancreatic, non-small cell lung, head and neck, ovarian, and urothelial cancers. Eligible adults must have histologically or cytologically confirmed advanced/metastatic disease with measurable disease per RECIST 1.1 (except mCRPC limited to bone) and must meet specified prior-therapy and organ function criteria. Participants receive systemic GTB-5550 and are monitored for safety, tolerability, immune effects, and any signs of anti-tumor activity.

Who should consider this trial

Good fit: Adults (≥18) with advanced or metastatic cancers that commonly express B7-H3 who have failed, are intolerant of, or are ineligible for standard therapies and meet organ function and performance-status requirements are the intended participants.

Not a fit: Patients whose tumors do not express B7-H3, who have inadequate organ function or ECOG >2, or who do not meet the prior-therapy requirements are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, GTB-5550 could boost and sustain patients' own NK cells to reduce tumors that express B7-H3 and provide a new option for people with limited treatments.

How similar studies have performed: Tri-specific NK engagers and IL-15–based NK stimulators are novel in humans with encouraging preclinical data and limited early clinical signals from related NK-activating approaches, but large-scale clinical success has not yet been established.

Eligibility criteria

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.

Where this trial is running

Minneapolis, Minnesota

• Masonic Cancer Center at University of Minnesota — Minneapolis, Minnesota, United States (RECRUITING)

Study contacts

• Study coordinator: Nicholas Zorko, MD

Conditions: Tri-specific Killer Engager, Solid Tumor, Advanced Solid Tumor, TriKE, GTB-5550