GTB-5550 in 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 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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor; Advanced Solid Tumor; Tri-specific Killer Engager
• Intervention / Treatment: Drug: GTB-5550

Detailed Description

Enrollment is limited to the following tumor types:

• castration-resistant prostate cancer (CRPC)
• breast cancer (any ER/PR or HER2 status)
• pancreatic cancer
• non-small cell lung cancer (NSCLC)
• squamous cell carcinoma of the head and neck (SCCHN), including molecularlyconfirmed FA patients
• epithelial ovarian cancer (OC), including fallopian tube and primary peritoneal cancer
• bladder (urothelial) cancer (UC)
• Prostate cancer requires failing at least one line of prior therapy in the castrate resistant setting.
• SCCHN patients with a molecularly-confirmed diagnosis of FA are permitted to enroll on the trial if they have unresectable locally advanced or metastatic SCCHN which is ineligible for or has failed radiation therapy. All other diagnoses require failing at least two lines of prior therapy given either in the recurrent and/or metastatic setting.

The camelid (cam) anti-CD16/WT IL-15/cam anti-B7-H3 Tri-Specific Killer Engager (camB7-H3 TriKE, also referred to as GTB-5550) is a single chain recombinant TriKE comprised of three components joined by flexible linkers to form a molecule: 1) an arm that engages the CD16 activating receptor (cam anti-CD16) on natural killer (NK) cells; 2) a wildtype IL-15 (WT IL-15) linker arm to drive NK cell proliferation, priming, and survival; and 3) an arm that specifically engages B7-H3 (cam anti-B7-H3) to target the tumor cells.

The study is performed in two sequential components as follows:

1. Phase 1a: Dose escalation, open-label component testing up to 6 dose levels of GTB-5550 to identify the MTD using an adaptation of the BOIN design starting with 2 patient cohorts.
2. Phase 1b: Dose expansion component to confirm the MTD identified in the Phase 1a trial across 7 distinct metastatic disease cohorts (castration-resistant prostate cancer, ovarian cancer, breast cancer, head and neck cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer) and further evaluate its tolerability assuming the toxicity rates are similar across the groups.

GTB-5550 is administered by subcutaneous (SQ) injection in the abdominal area for 5 consecutive days (i.e. Monday-Friday) for Cycle 1 Days 1-5 and Days 8-12, followed by 2 weeks off treatment. Starting with Cycle 2 Day 1 and beyond, treatment will be 3 times 2025LS049: GTB-5550 TriKE® for Select Advanced Solid Tumors That Failed Prior Therapy March 19, 2026 Page 27 of 86 confidential per week (but not on 3 consecutive days) for 2 weeks followed by 2 weeks off treatment.

One treatment cycle equals 4 weeks (28 days).

A minimum of 2 cycles is planned unless medically contraindicated or the participant wishes to discontinue earlier. Patient appropriate disease reassessment is done after 2 cycles (56 days) and every 8 weeks (+/- 1 week) thereafter. Treatment may continue until disease progression, unacceptable toxicity, patient refusal, or treatment is no longer in the best interest of the patient. Patients are followed for 12 months from the 1st dose of GTB-5550 to determine PFS and OS. The primary analysis will be intent-to-treat from the point of 1st injection of GTB-5550 both for toxicity and efficacy.

• Study Type: Interventional
• Enrollment (Estimated): 175
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Nicholas Zorko, MD; Phone Number: 612-625-3051; Email: zorko004@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • Masonic Cancer Center at University of Minnesota
      • Contact: Nicholas Zorko, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level Cohort -1; Patients with histologically or cytologically confirmed advanced/metastatic cancer. Patients will receive 90 µg (or 20 µL) of GTB-5550.	Drug: GTB-5550; GTB-5550 is given as a subcutaneous (SQ) injection in the abdominal area at the patient-assigned dose once a day for 5 consecutive days for 2 weeks in a row (i.e. Day 1-5 and Day 8-12) followed by 2 weeks of no treatment. This 4-week period equals 1 treatment cycle, or 28 days. Starting with Cycle 2 and beyond, this will be repeated with three times per week dosing for weeks 1 and 2 of the cycle (but not on 3 consecutive days) followed by 2 weeks of no treatment.; Other Names: Camelid Nanobody B7-H3 Tri-Specific Killer Engager (camB7-H3 TriKE®)
Experimental: Dose Level Cohort 1; Patients with histologically or cytologically confirmed advanced/metastatic cancer. Patients will receive 270 µg (or 60 µL) of GTB-5550.	Drug: GTB-5550; GTB-5550 is given as a subcutaneous (SQ) injection in the abdominal area at the patient-assigned dose once a day for 5 consecutive days for 2 weeks in a row (i.e. Day 1-5 and Day 8-12) followed by 2 weeks of no treatment. This 4-week period equals 1 treatment cycle, or 28 days. Starting with Cycle 2 and beyond, this will be repeated with three times per week dosing for weeks 1 and 2 of the cycle (but not on 3 consecutive days) followed by 2 weeks of no treatment.; Other Names: Camelid Nanobody B7-H3 Tri-Specific Killer Engager (camB7-H3 TriKE®)
Experimental: Dose Level Cohort 2; Patients with histologically or cytologically confirmed advanced/metastatic cancer. Patients will receive 900 µg (or 200 µL) of GTB-5550.	Drug: GTB-5550; GTB-5550 is given as a subcutaneous (SQ) injection in the abdominal area at the patient-assigned dose once a day for 5 consecutive days for 2 weeks in a row (i.e. Day 1-5 and Day 8-12) followed by 2 weeks of no treatment. This 4-week period equals 1 treatment cycle, or 28 days. Starting with Cycle 2 and beyond, this will be repeated with three times per week dosing for weeks 1 and 2 of the cycle (but not on 3 consecutive days) followed by 2 weeks of no treatment.; Other Names: Camelid Nanobody B7-H3 Tri-Specific Killer Engager (camB7-H3 TriKE®)
Experimental: Dose Level Cohort 3; Patients with histologically or cytologically confirmed advanced/metastatic cancer. Patients will receive 2700 µg (or 600 µL) of GTB-5550.	Drug: GTB-5550; GTB-5550 is given as a subcutaneous (SQ) injection in the abdominal area at the patient-assigned dose once a day for 5 consecutive days for 2 weeks in a row (i.e. Day 1-5 and Day 8-12) followed by 2 weeks of no treatment. This 4-week period equals 1 treatment cycle, or 28 days. Starting with Cycle 2 and beyond, this will be repeated with three times per week dosing for weeks 1 and 2 of the cycle (but not on 3 consecutive days) followed by 2 weeks of no treatment.; Other Names: Camelid Nanobody B7-H3 Tri-Specific Killer Engager (camB7-H3 TriKE®)
Experimental: Dose Level Cohort 4; Patients with histologically or cytologically confirmed advanced/metastatic cancer. Patients will receive 5400 µg (or 1200 µL) of GTB-5550.	Drug: GTB-5550; GTB-5550 is given as a subcutaneous (SQ) injection in the abdominal area at the patient-assigned dose once a day for 5 consecutive days for 2 weeks in a row (i.e. Day 1-5 and Day 8-12) followed by 2 weeks of no treatment. This 4-week period equals 1 treatment cycle, or 28 days. Starting with Cycle 2 and beyond, this will be repeated with three times per week dosing for weeks 1 and 2 of the cycle (but not on 3 consecutive days) followed by 2 weeks of no treatment.; Other Names: Camelid Nanobody B7-H3 Tri-Specific Killer Engager (camB7-H3 TriKE®)
Experimental: Dose Level Cohort 5; Patients with histologically or cytologically confirmed advanced/metastatic cancer. Patients will receive 9000 µg (or 2000 µL) of GTB-5550.	Drug: GTB-5550; GTB-5550 is given as a subcutaneous (SQ) injection in the abdominal area at the patient-assigned dose once a day for 5 consecutive days for 2 weeks in a row (i.e. Day 1-5 and Day 8-12) followed by 2 weeks of no treatment. This 4-week period equals 1 treatment cycle, or 28 days. Starting with Cycle 2 and beyond, this will be repeated with three times per week dosing for weeks 1 and 2 of the cycle (but not on 3 consecutive days) followed by 2 weeks of no treatment.; Other Names: Camelid Nanobody B7-H3 Tri-Specific Killer Engager (camB7-H3 TriKE®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	The primary objective is to identify one of the six dose-level strategies of GTB-5550 (cam anti-CD16/WT IL 15/cam anti-B7-H3 TriKE) that corresponds to the desired maximum toxicity rate of less of equal to 20%, defining the MTD.	1 year

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborators: GT Biopharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2026
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2032

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: TriKE; GTB-5550
• Other Study ID Numbers: 2025LS049; W81XWH-20-1-0659 (Other Grant/Funding Number: DoD); HT9425-25-1-0438 (Other Grant/Funding Number: DoD); W81XWH-22-1-0242 (Other Grant/Funding Number: DoD)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No