A Safety Study of SGN-CD48A in Patients With Multiple Myeloma

A Phase 1 Study of SGN-CD48A in Patients With Relapsed or Refractory Multiple Myeloma

This study will test the safety and activity of SGN-CD48A in patients with multiple myeloma. SGN-CD48A will be given on Days 1, 8, and 15 of a 28-day cycle. Prior to protocol amendment 2, SGN-CD48A was given every 3 weeks.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: SGN-CD48A

Detailed Description

This study is designed to evaluate the safety, tolerability, and antitumor activity of SGN-CD48A in patients with relapsed or refractory multiple myeloma. This study will be conducted in 2 parts:

1. Dose escalation: This part will evaluate increasing doses of SGN-CD48A to identify the maximum tolerated dose.

   The first group of patients enrolled on the study will receive the lowest dose of SGN-CD48A. Once this dose is shown to be safe, a second group of patients will be enrolled at the next higher dose. Patients will continue to be enrolled in groups receiving increasing doses until the maximum tolerated dose level is reached. Patients can only be enrolled into a higher dose level once the lower doses have been demonstrated safe. Dose escalation will be conducted using a modified toxicity probability interval (mTPI) study design.

2. Dose expansion: This part will further evaluate the safety, tolerability, and antitumor activity of up to 2 dose levels of SGN-CD48A shown to be safe in the first part of the trial.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94134
      • University of California at San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania / Perelman Center for Advanced Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of MM requiring systemic therapy (per the International Myeloma Working Group [IMWG])
• Patients must not have other therapeutic options known to provide clinical benefit in MM available to them. Prior lines of therapy must include at least a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody.
• Measureable disease, as defined by at least one of the following: serum M protein 0.5 g/dL or higher, urine M protein 200 mg/24 hour or higher, and serum immunoglobulin free light chain 10 mg/dL or higher and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Adequate hematologic, renal, and hepatic function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than 3 months
• A negative pregnancy test (for females of childbearing potential)
• Patients must provide written consent

Exclusion Criteria:

• Pre-existing peripheral neuropathy Grade 2 or higher
• History of malignancy other than MM within the past 3 years
• Active cerebral/meningeal disease related to the underlying malignancy
• Uncontrolled Grade 3 or higher infection
• Known to be positive for HIV or hepatitis B, or known to have active hepatitis C infection
• Previous allogeneic stem cell transplant
• History of cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with congestive heart failure within the last 6 months
• Treatment with any known P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days prior to the first dose of study drug
• Prior antitumor therapy that is not completed at least 4 weeks prior to first dose of study drug, or at least 2 weeks if progressing. Prior CAR T-cell therapy must be completed 8 weeks before first dose of study drug.
• Females who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SGN-CD48A	Drug: SGN-CD48A; Intravenous (IV) infusion on days 1, 8, and 15 of a 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of laboratory abnormalities	Through 1 month following last dose
Type, incidence, severity, seriousness, and relatedness of adverse events	Through 1 month following last dose
Incidence of dose limiting toxicity	Through 3 weeks following first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of antitherapeutic antibodies		Through 1 month following last dose
Overall survival		Up to approximately 3 years
Progression-free survival		Up to approximately 3 years
Objective response rate	The proportion of patients with stringent complete response, complete response, very good partial response, or partial response per investigator	Through 1 month following last dose
Complete response rate	The proportion of patients with stringent complete response or complete response per investigator	Through 1 month following last dose
Duration of objective response		Up to approximately 3 years
Duration of complete response		Up to approximately 3 years
Blood concentrations of SGN-CD48A and metabolites		Through 1 month following last dose

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Director: Suzanne McGoldrick, MD, MPH, Seagen Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2018
• Primary Completion (Actual): August 23, 2019
• Study Completion (Actual): August 23, 2019

Study Registration Dates

• First Submitted: December 13, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 20, 2017

Study Record Updates

• Last Update Posted (Actual): September 18, 2019
• Last Update Submitted That Met QC Criteria: September 16, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Multiple myeloma; Antibody-drug conjugate
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: SGN48A-001

Drug and device information, study documents

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