Clinical trial NCT03379584: A Safety Study of SGN-CD48A in Patients With Multiple Myeloma
Official title: A Phase 1 Study of SGN-CD48A in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
Antibody-drug conjugate
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2017-12-20
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Type, incidence, severity, seriousness, and relatedness of adverse events
timeFrame: Through 1 month following last dose
measure: Incidence of laboratory abnormalities
timeFrame: Through 1 month following last dose
measure: Incidence of dose limiting toxicity
timeFrame: Through 3 weeks following first dose
Secondary outcomes:
measure: Objective response rate
timeFrame: Through 1 month following last dose
measure: Complete response rate
timeFrame: Through 1 month following last dose
measure: Duration of objective response
timeFrame: Up to approximately 3 years
measure: Duration of complete response
timeFrame: Up to approximately 3 years
measure: Progression-free survival
timeFrame: Up to approximately 3 years
measure: Overall survival
timeFrame: Up to approximately 3 years
measure: Blood concentrations of SGN-CD48A and metabolites
timeFrame: Through 1 month following last dose
measure: Incidence of antitherapeutic antibodies
timeFrame: Through 1 month following last dose
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania / Perelman Center for Advanced Medicine
state: Pennsylvania
Study officials:
affiliation: Seagen Inc.
name: Suzanne McGoldrick, MD, MPH
role: STUDY_DIRECTOR
References: