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Study of the Safety and Efficacy of STI-6129 in Patients With Relapsed or Refractory Systemic AL Amyloidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04316442
Recruitment Status : Recruiting
First Posted : March 20, 2020
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
Sorrento Therapeutics, Inc.

Brief Summary:

The STI-6129-001 study is a three-stage, multicenter, open-label, dose-finding, phase 1 trial. It is designed primarily to identify the recommended phase 2 dose (RP2D) of STI-6129 by assessing the safety, preliminary efficacy and pharmacokinetics of this anti-CD38-Duostatin 5.2 antibody-drug conjugate (ADC) for the treatment of relapsed or refractory systemic AL amyloidosis.

The patients that will be treated with STI-6129 in this trial are relapsed or refractory systemic AL amyloidosis patients who have received prior lines of treatment.


Condition or disease Intervention/treatment Phase
Light Chain (AL) Amyloidosis Biological: STI-6129 Phase 1

Detailed Description:

This study is composed of three dosing plan stages. The initial stage of this trial is the dose-escalation stage. A standard dose-escalation 3+3 design will be utilized to identify a safe maximum tolerated dose (MTD) of STI-6129 in patients with relapsed or refractory systemic AL amyloidosis. After identification of the MTD, or the finding that the last dosing cohort is tolerated well (i.e., the maximum practical dose [MPD]), 12 patients will be enrolled to receive STI-6129 treatment at the MTD/MPD level to collect pharmacokinetic data ( the pharmacokinetic (PK) stage) to model a treatment schedule that achieves a stable effective serum concentration. Results from the dose-escalation stage and the pharmacokinetic stage will be analyzed to develop a treatment dose/schedule for treating 30 additional patients enrolled in the expansion stage.

Each patient enrolled will receive up to three 3-week cycles of STI-6129. After the treatment period, patients will be monitored for up to a year.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Dose-Escalation Study of the Safety and Efficacy of an Anti-CD38 Antibody Drug Conjugate (STI-6129) in Patients With Relapsed or Refractory Systemic AL Amyloidosis
Actual Study Start Date : November 13, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis

Arm Intervention/treatment
Experimental: STI-6129 infusion
Intravenous infusion to be given with prophylaxis for infusion reactions if necessary.
Biological: STI-6129
Three cycles of intravenous infusion of STI-6129 will be given (one infusion every three weeks).
Other Name: anti-CD38-Duostatin 5.2 antibody-drug conjugate (ADC)




Primary Outcome Measures :
  1. Safety and tolerability of STI-6129 in AL amyloidosis patients [ Time Frame: Baseline through study completion at up to 14 months ]
    Types, frequencies, and severities of adverse events (AEs) and the relationships of AEs to study drug; includes serious adverse events (SAEs), neurotoxicity, dose-limiting toxicities (DLTs), and laboratory abnormalities


Secondary Outcome Measures :
  1. Overall hematological response rate according to the 2012 Consensus Round Table response criteria [ Time Frame: Baseline through study completion at up to 14 months ]
    Proportion of subjects with Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR) and Progressive Disease (PD)

  2. Organ response rates (cardiac, renal, hepatic, peripheral nervous system) according to the 2012 Consensus Round Table response criteria [ Time Frame: Baseline through study completion at up to 14 months ]
    Organ response rates (cardiac, renal, hepatic, peripheral nervous system) according to the 2012 Consensus Round Table response criteria

  3. Correlation of treatment response (organ responses and hematological response) with disease severity based on the 2012 revised Mayo Clinic staging system for AL amyloidosis [ Time Frame: Baseline through study completion at up to 14 months ]
    Correlation of treatment response (organ responses and hematological response) with disease severity based on the 2012 revised Mayo Clinic staging system for AL amyloidosis

  4. Plasma levels of the total antibody plus conjugated toxin (STI-6129) and the free toxin (Duostatin 5.2) [ Time Frame: Day 1 to day 63 ]
    Plasma levels of the total antibody plus conjugated toxin (STI-6129) and the free toxin (Duostatin 5.2) by ELISA and mass spectrophotometry assays, respectively, at pre-dose and various time points post-dose



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of AL amyloidosis by tissue biopsy of an involved organ, or a surrogate site such as abdominal fat demonstrating amyloid deposition by mass spectrometry
  • The presence of a monoclonal light chain protein in serum
  • Relapsed or refractory AL amyloidosis is defined as patients who have received ≥ 2 lines of treatment. Patients must have received at least one proteasome inhibitor during their prior therapy. Patients who have received prior daratumumab treatment or prior stem cell transplantation remain eligible. Patients may have relapsed with disease progression or have been refractory to their last prior line of treatment. Progression of disease that develops > 60 days after the last dose of a treatment regimen in a patient who achieved at least a partial response (PR) defines a relapse. Refractory systemic AL amyloidosis is defined as the development of disease progression during therapy with an anti-AL amyloidosis treatment regimen or within 60 days of the last dose of an anti-AL amyloidosis treatment regimen or the achievement of less than a PR after ≥ 2 cycles
  • Measurable disease defined as the finding by serum-free light chain (FLC) assay that the difference between the involved and uninvolved FLC (dFLC) is ≥ 50 mg/L
  • Pulse oximetry ≥ 92% on room air
  • ECOG performance status of 0, 1, or 2
  • Willing to comply with the study schedule and all other protocol requirements
  • Females of childbearing potential (FCBP) must have 2 negative pregnancy tests prior to treatment. All heterosexually active FCBP and all heterosexually active male patients must agree to use effective methods of birth control throughout the study

Exclusion Criteria:

  • Isolated vascular amyloid in a bone marrow biopsy or a plasmacytoma specimen or isolated soft tissue involvement (localized AL amyloidosis)
  • Presence of non-AL amyloidosis
  • A diagnosis of multiple myeloma
  • A diagnosis of other malignancies if the malignancy has required therapy within the last 3 years or is not in complete remission. Exceptions are non-metastatic basal cell or squamous cell carcinomas of the skin or prostate cancer that does not require treatment
  • Treatment with an allogeneic hematopoietic stem cell transplantation (HSCT) within 6 months prior to the planned infusion of STI-6129, or active graft-versus-host disease (GVHD) following the allogeneic transplant, or a requirement for currently receiving immunosuppressive therapy following the allogeneic transplant
  • Revised Mayo Clinic AL amyloidosis stage > 3
  • New York Heart Association (NYHA) class > 2
  • Left ventricular ejection fraction (LVEF) < 40%
  • Patients with mean left ventricular wall thickness ≥ 12 mm and/or intraventricular septal thickness > 25 mm by echocardiogram in the absence of hypertension or valvular heart disease
  • Patients with NT-proBNP ≥ 1800 ng/L or BNP ≥ 400 ng/L, or cTNT ≥ 0.025 μg/L will be excluded in the dose-escalation stage of the study and can only be included in the PK and expansion stages after evaluation by cardiology and discussion with the principle investigator regarding the risk associated with the treatment
  • Abnormal baseline hematological laboratory results at Screening:

    • Hemoglobin < 8.0 g/dL
    • Platelet count < 50,000/μL
    • Absolute neutrophil count (ANC) < 1000/μL
  • Abnormal baseline chemistry laboratory results at Screening:

    • Serum creatinine ≥ 2.0 mg/dL or estimated creatinine clearance < 60 mL/min (using the Cockcroft-Gault equation)
    • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x the upper limit of normal (ULN) or serum total bilirubin > 1.5x ULN (except for patients in whom hyperbilirubinemia is attributed to Gilbert's Syndrome)
  • INR or aPTT > 1.5x ULN within 1 week prior to the infusion of STI-6129, unless on a stable dose of an anticoagulant
  • Pregnant or breastfeeding
  • Active bacterial, viral, or fungal infection within 72 hours of the infusion of STI-6129; patients with ongoing use of prophylactic antibiotics, antifungal agents, or antiviral agents remain eligible as long as there is no evidence of active infection
  • Have human immunodeficiency virus (HIV) infection, human T-cell leukemia virus type 1 (HTLV1) infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or are at risk for HBV reactivation (at risk for HBV reactivation is defined as being HBs antigen positive, or anti-HBc-antibody positive), or are positive for HBV deoxyribonucleic acid (DNA). HCV ribonucleic acid (RNA) must be undetectable by laboratory test
  • QTcF > 470 msec on a baseline ECG
  • Any condition including the presence of laboratory abnormalities that places the patient at unacceptable risk if the patient was to participate in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04316442


Contacts
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Contact: Ying Yan, MD MS 858-203-4100 ext 4183 yyan@sorrentotherapeutics.com
Contact: Mike Royal, MD JD MBA 858-203-4100 ext 4146 mroyal@sorrentotherapeutics.com

Locations
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United States, New York
Columbia University - Herbert Irving Comprehensive Cancer Center Recruiting
New York, New York, United States, 10032
Contact: Niha Mamillapalli    212-342-3849    nm3216@cumc.columbia.edu   
Principal Investigator: Suzanne Lentzsch, MD PHD         
Sponsors and Collaborators
Sorrento Therapeutics, Inc.
Investigators
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Principal Investigator: Suzanne Lentzsch, MD Columbia University
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Responsible Party: Sorrento Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04316442    
Other Study ID Numbers: STI-6129-001
First Posted: March 20, 2020    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Immunoglobulin Light-chain Amyloidosis
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Paraproteinemias
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs