An Open-Label Study of the Safety of an Anti-CD38 Antibody Drug Conjugate (STI-6129) in Patients With AL Amyloidosis

NCT05692908 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 38ADC-RRAL-102-SWE
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 1 open-label, dose escalation trial designed to identify the recommended phase 2 dose of STI-6129 by assessing the safety, preliminary efficacy, and immunogenicity in subjects with relapsed or refractory systemic AL Amyloidosis

Conditions

Light Chain (AL) Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Safety of STI-6129

  Safety as assessed by incidence of adverse events (AEs), severe AEs (SAEs), DLTs, neurotoxicity and laboratory abnormalities using the Common Terminology Criteria for Adverse Events (CTCAE Version 5)

  Baseline through study completion at up to approximately 24 months

Secondary Outcomes (4)

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

  Baseline through study completion at up to approximately 24 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 approximately 24 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 approximately 24 months

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

  Baseline through study completion at up to approximately 24 months

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:

• \. Age ≥ 18 years.
• \. 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 and/or urine
• \. Relapsed or refractory (R/R) AL amyloidosis is patients who have exhausted standard of care treatment. Patients who have received prior CD38-directed monoclonal antibody (e.g. daratumumab, isatuximab) 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. 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 by the following: the finding by serum FLC assay that the difference between the involved and uninvolved FLC (dFLC) is ≥ 40 mg/L
• \. Pulse oximetry ≥ 92% on room air
• \. ECOG performance status of 0, 1, or 2
• \. Be willing and able to comply with the study schedule and all other protocol requirements
• \. Willing to follow contraception guidelines: c. If a female, be sterile (surgically or biologically)\* or at least one year post-menopausal, or have a monogamous partner who is surgically sterile, or have a same sex partner, or if in a heterosexual relationship, must agree to do the following during the study after completing IP dosing:
• Practice abstinence (only considered an acceptable method of contraception when it is in line with the participants' usual and preferred lifestyle)
• Use at least one of the following medically acceptable methods of birth control:
• Hormonal methods as follows:
• Combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• Progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• Intrauterine devices

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 or in situ cancer that does not require treatment or is well under control
• \. 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 \> 3
• \. Left ventricular ejection fraction (LVEF) \< 40%.
• \. Patients with mean left ventricular wall thickness ≥ 15 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, cTnT ≥ 0.025 mcg/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
• \. The following baseline hematological laboratory results at Screening (these results must be independent of blood product or hematopoietic growth factor support):
• Hemoglobin \< 8.0 g/dL
• Platelet count \< 50,000/μL
• Absolute neutrophil count (ANC) \< 1000/ μL
• \. The following baseline chemistry laboratory results at Screening:

Sponsors & Collaborators

• Sorrento Therapeutics, Inc.: lead

MeSH Terms

Conditions

Amyloidosis

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

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

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: January 20, 2023
• Study Start: September 1, 2023
• Primary Completion: September 1, 2024
• Study Completion: November 1, 2024
• Last Updated: April 28, 2023

Record last verified: 2023-04