GTB-3550 (CD16/IL-15/CD33) Tri-Specific Killer Engager (TriKE™) for High Risk Heme Malignancies

• ClinicalTrials.gov Identifier: NCT03214666
• Recruitment Status: Recruiting
• First Posted: July 11, 2017
• Last Update Posted: June 11, 2020
• Sponsor: GT Biopharma, Inc.
• Information provided by (Responsible Party): GT Biopharma, Inc.

Tracking Information

• First Submitted Date: July 7, 2017
• First Posted Date: July 11, 2017
• Last Update Posted Date: June 11, 2020
• Actual Study Start Date: January 1, 2020
• Estimated Primary Completion Date: February 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 1, 2019)

• Phase I Maximum Tolerated Dose (MTD) of GTB-3550 TriKE™ Finding [ Time Frame: Day 28 ]
  To identify the maximum tolerated dose (MTD) of GTB-3550 TriKE™ defined as the dose level that most closely corresponds to a dose limiting toxicity rate (DLT) of 20%
• Phase II Incidence of complete and partial remission due to GTB-3550 TriKE™ treatment [ Time Frame: Day 42 ]
  The incidence of clinical response by Day 42 after the start of the 1st infusion.

Original Primary Outcome Measures (submitted: July 10, 2017)

• Phase I Maximum Tolerated Dose (MTD) of 161533 TriKE™ Finding [ Time Frame: Day 28 ]
  To identify the maximum tolerated dose (MTD) of 161533 TriKE™ defined as the dose level that most closely corresponds to a dose limiting toxicity rate (DLT) of 20%
• Incidence of complete and partial remission due to 161533 TriKE treatment [ Time Frame: Day 42 ]
  The incidence of clinical response by Day 42 after the start of the 1st infusion.

Current Secondary Outcome Measures (submitted: October 1, 2019)

• Incidence of GTB-3550 TriKE™ Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Day 28 ]
  The incidence of unexpected events in relation to GTB-3550 TriKE™
• Overall Survival (OS) [ Time Frame: 6 Months ]
  Incidence of survival of patients treated on this study

Original Secondary Outcome Measures (submitted: July 10, 2017)

• Incidence of 161533 TriKE™ Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Day 28 ]
  The incidence of unexpected events in relation to 161533 TriKE™
• Overall Survival (OS) [ Time Frame: 6 Months ]
  Incidence of survival of patients treated on this study

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GTB-3550 (CD16/IL-15/CD33) Tri-Specific Killer Engager (TriKE™) for High Risk Heme Malignancies
• Official Title: GTB-3550 (CD16/IL-15/CD33)Tri-Specific Killer Engager (TriKE™) for the Treatment of High Risk Myelodysplastic Syndromes, Refractory/Relapsed Acute Myeloid Leukemia and Advanced Systemic Mastocytosis
• Brief Summary: This is a single center Phase I/II clinical trial of GTB-3550 (CD16/IL-15/CD33) tri-specific killer cell engager (TriKE™) for the treatment of CD33-expressing high risk myelodysplastic syndromes, refractory/relapsed acute myeloid leukemia or advanced systemic mastocytosis. The hypothesis is that GTB-3550 TriKE™ will induce natural killer cell function by targeting malignant cells as well as CD33+ myeloid derived suppressor cells (MDSC) which contribute to tumor induced immunosuppression. Because CD16 is the most potent activating receptor on NK cells, this single agent may induce a targeted anti-CD33+ tumor response.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• High-risk Myelodysplastic Syndromes
• Acute Myelogenous Leukemia
• Systemic Mastocytosis
• Mast Cell Leukemia

Intervention

• Drug: GTB-3550 TriKE™ Phase I

  Bolus Test Dose: 20% of Daily Continuous Infusion Dose.

  The 1st two patients will be assigned dose level 1. The study statistician will assign each new cohort of 2 patients to the most appropriate dose level based on updated toxicity probabilities.

  • Dose level 1 - 5 μg/kg/day
  • Dose level 2 - 10 μg/kg/day
  • Dose level 3 - 25 μg/kg/day
  • Dose level 4 - 50 μg/kg/day
  • Dose level 5 - 100 μg/kg/day
  • Dose level 6 - 200 μg/kg/day
  Other Name: CD16/IL-15/CD33
• Drug: GTB-3550 TriKE™ Phase II
  Patients will receive the maximum tolerated dose (MTD) established during Phase I with monitoring guidelines to stop the study early for excessive toxicity.
  Other Name: CD16/IL-15/CD33

Study Arms

• Experimental: GTB-3550 TriKE™ (Phase I: Dose Finding Component)
  Patients receive a single course of GTB-3550 TriKE™ at their assigned dose as 3 weekly treatment blocks. Each block consists of four consecutive 24 hour continuous infusions (over approximately 96 hours) of GTB-3550 TriKE™ followed by a 72 hour break after Block #1 and #2. All treatment is given as an inpatient. The assigned dose will be calculated on a weight obtained within 5 days prior to or on day of the 1st dose. The dose is not be recalculated for subsequent treatment blocks.
  Intervention: Drug: GTB-3550 TriKE™ Phase I
• Experimental: GTB-3550 TriKE™ Only (Phase II: Extended Component)
  The treatment schedule is identical to the dose finding component. The extended component uses a Simon's MiniMax two-stage design for continued enrollment using the maximum tolerated dose (MTD) established during Phase I with monitoring guidelines to stop the study early for excessive toxicity.
  Intervention: Drug: GTB-3550 TriKE™ Phase II

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 10, 2017): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 1, 2025
• Estimated Primary Completion Date: February 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria: Eligible Diseases

• Diagnosis of one of the following CD33-expressing myeloid malignancies with no good standard of care treatment options including:

• High Risk Myelodysplastic Syndromes (MDS) progressive on two or more prior regimens and requiring treatment that meets at least one of the following:

  • Revised International Prognostic Scoring System (R-IPSS) Category (refer to Appendix II): INT-2 or High Risk
  • R-IPSS High or Very High Risks
  • WHO Classification: RAEB-1 or RAEB-2
  • Poor and very-poor risk cytogenetic abnormality as defined by the R-IPSS cytogenetic classifications
  • WHO Based Prognostic Scoring System (WPSS): High or Very High Risk
• Therapy related MDS and not a candidate for induction chemotherapy. Would be eligible if treated with induction chemotherapy and had an inadequate treatment response.

• Refractory or Relapsed Acute Myelogenous Leukemia (AML) meeting at least one of the following:

  • Refractory AML defined as failure to achieve remission after at least 3 induction attempts

  • Relapsed AML

    • Not a candidate for stem cell transplant (HSCT), at least one re-induction attempt required.
    • Prior HSCT relapse beyond 3 months may be included only if off immunosuppression for a minimum of 4 weeks and do not have GVHD.
• Advanced systemic mastocytosis (defined as mast cell leukemia, aggressive systemic mastocytosis, and systemic mastocytosis associated with hematologic neoplasm) may enroll without any prior treatment, given there is no standard established therapy.

Inclusion Criteria: Age, Performance Status, Organ Function, Contraception Use

• At least 18 years of age
• Karnofsky score ≥ 70% (Appendix I)

• Adequate organ function within 14 days (30 days for cardiac and pulmonary) of study enrollment defined as:

  • Renal: an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2 using Modification of Diet in Renal Disease equation
  • Hepatic: AST, ALT, and alkaline phosphatase ≤ 3 x upper limit of normal and total bilirubin ≤ 1.5 х upper limit of normal range (ULN)
  • Pulmonary function: DLCO corrected (ml/min/mm Hg) defined as no more than 5 units below lower limit of normal (CTCAE v5 Grade 1 carbon monoxide diffusing capacity decreased) based on patient's height, weight, and gender as reported by the institutional pulmonary function lab.
  • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia; left ventricular ejection fraction ≥ 45% by echocardiogram, MUGA or cardiac MRI.
• Absolute lymphocyte count (ALC) ≥ 200 cells/mm³ and absolute circulating CD56+/CD3- NK cell count >25 cells/μl within the 14 days prior to start of therapy
• Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment
• Participant provides voluntary written consent signed before performance of any study-related procedure not part of normal medical care

Exclusion Criteria

• New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan unless cleared for study by Pulmonary. Infiltrates attributed to infection must be stable/improving with associated clinical improvement after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
• Uncontrolled bacterial, fungal or viral infections, known history of HIV
• Active Hepatitis B or Hepatitis C (virus detectable by PCR) - chronic asymptomatic viral hepatitis is allowed
• Pregnant or breast feeding. The effect of GTB-3550 TriKE™ on the fetus is unknown. Females of childbearing potential must have a blood test or urine study within 7 days prior to enrollment to rule out pregnancy - must be repeated if not within 7 days of treatment initiation
• History of central nervous system malignancy or symptoms of active CNS disease
• A family history of long QT syndrome or with a QTc interval > 480 msec at screening
• Currently taking medications known to prolong QT/QTc interval as the potential risk of QT/QTc prolongation is unknown in humans (refer to Appendix V for a list of prohibited medications for eligibility)
• A candidate for potentially curative therapy, including hematopoietic cell transplant
• Unwilling to remain in the greater Twin Cities metropolitan area through at least Day 29

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jeffrey S Miller, MD; 612-625-7409; mille011@umn.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03214666
• Other Study ID Numbers: 2015LS167; HM2015-39 ( Other Identifier: University of Minnesota Masonic Cancer Center )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: GT Biopharma, Inc.
• Study Sponsor: GT Biopharma, Inc.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Erica D Warlick, MD; Masonic Cancer Center, University of Minnesota

• PRS Account: GT Biopharma, Inc.
• Verification Date: June 2020