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

NCT04316442 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: STI-6129-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

The STI-6129-001 study is a three-stage, multicenter, open-label, dose-finding, phase 1b/2a 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.

Conditions

Light Chain (AL) Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of STI-6129 in AL amyloidosis patients

  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

  Baseline through study completion at up to 14 months

Secondary Outcomes (4)

• Overall hematological response rate according to the 2012 Consensus Round Table response criteria

  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

  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

  Baseline through study completion at up to 14 months

• Plasma levels of the total antibody plus conjugated toxin (STI-6129) and the free toxin (Duostatin 5.2)

  Day 1 to day 63

Study Arms (1)

STI-6129 infusion

EXPERIMENTAL

Intravenous infusion to be given with prophylaxis for infusion reactions if necessary.

Biological: STI-6129

Interventions

STI-6129 BIOLOGICAL

Four cycles of intravenous infusion of STI-6129 will be given (one infusion every four weeks).

Also known as: anti-CD38-Duostatin 5.2 antibody-drug conjugate (ADC)

STI-6129 infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Sorrento Therapeutics, Inc.: lead

Study Sites (4)

City of Hope National Medical Center

Duarte, California, 91010, United States

RECRUITING

Boston Medical Center

Boston, Massachusetts, 02118, United States

RECRUITING

Barbara Ann Karmanos Cancer Institute Wertz Clinic

Detroit, Michigan, 48201, United States

RECRUITING

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Amyloidosis

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Vaishali Sanchorawala, MD

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

• Michael Rosenzweig, MD

  City of Hope National Medical Center

  PRINCIPAL INVESTIGATOR

• Jeffrey Zonder, MD

  Barbara Ann Karmanos Cancer Institute Wertz Clinic

  PRINCIPAL INVESTIGATOR

• Anita D'Souza, MD

  Froedtert Hospital & the Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Yan, MD MS

CONTACT

858-203-4100; yyan@sorrentotherapeutics.com

Mike Royal, MD JD MBA

CONTACT

858-203-4100; mroyal@sorrentotherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2020
• First Posted: March 20, 2020
• Study Start: April 1, 2021
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: January 17, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)