Study of Vadastuximab Talirine (SGN-CD33A; 33A) in Combination With Azacitidine in Patients With Previously Untreated Higher Risk MDS

Study Overview
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Brief Summary
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This is a phase 1/2 study to evaluate the combination of vadastuximab talirine (SGN-CD33A; 33A) and azacitidine in subjects with previously untreated International Prognostic Scoring System (IPSS) Intermediate-2 or high risk myelodysplastic syndrome (MDS).

Detailed Description
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In the phase 1 portion of the study, escalating doses of 33A will be evaluated in combination with azacitidine, and a dose of 33A will be selected to proceed to phase 2. The phase 2 portion of the study is randomized, double-blind and placebo-controlled; it is designed to compare the overall response rate (ORR) between 2 study arms.

Official Title
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A Phase 1/2 Study of Vadastuximab Talirine (SGN-CD33A) in Combination With Azacitidine in Patients With Previously Untreated International Prognostic Scoring System (IPSS) Intermediate-2 or High Risk Myelodysplastic Syndrome (MDS)

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: vadastuximab talirine
* Drug: Azacitidine
* Drug: Placebo (for 33A)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with cytologically/histologically confirmed MDS according to the World Health Organization (WHO) 2008 classification. Previously untreated for Myelodysplastic Syndrome (MDS) Age ≥18 years of age. Eligible for therapy with azacitidine. Life expectancy of at least 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Adequate baseline laboratory parameters. Exclusion Criteria: Received prior treatment for MDS with lenalidomide or hypomethylating agents (HMAs). History of one of the following myeloproliferative neoplasms: essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, eg, prostate or breast cancer). Candidates for allogeneic stem cell transplant at the time of screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 33A + azacitidine<br>Vadastuximab talirine plus azacitidine | Drug: vadastuximab talirine<br>* Intravenous (IV) push every 4 weeks<br>* Other names: SGN-CD33A;Drug: Azacitidine<br>* 75 mg/m^2 given intravenously or subcutaneously for 7 days every 4 weeks<br>|
| Active Comparator: Placebo + azacitidine<br>placebo plus azacitidine | Drug: Azacitidine<br>* 75 mg/m^2 given intravenously or subcutaneously for 7 days every 4 weeks<br>Drug: Placebo (for 33A)<br>* Placebo supplied in single-use vials matching 33A, IV push every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Outcome Measure: Recommended Dose of Vadastuximab Talirine for the Phase 2 Portion of the Study | A recommended dose of vadastuximab talirine was not identified in Phase 1 due to study termination. Number of dose delays and reductions are reported in lieu of a dose recommendation. | Up to 1 year | 
| Phase 2 Outcome Measure: Overall Response Rate for the Phase 2 Portion of the Study |  | N/A - End point not assessed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the Combination of Vadastuximab Talirine and Azacitidine Measured by the Number of Participants With Adverse Events and Laboratory Abnormalities | As defined by the number of participants with adverse events and laboratory abnormalities. Participants are included only once per row, even if the participant experienced multiple events applicable to the category. | Up to 1 year | 
| Complete Response Rate (CR) | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the CR rate, as defined by the 2006 IWG criteria for MDS. | N/A - End point not assessed | 
| Hematologic Improvement (HI) Rate | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the HI rate, as defined by the 2006 IWG criteria for MDS. | N/A - End point not assessed | 
| Duration of Response (DOR) Rate | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first observation of response (CR, PR, or Marrow CR) to disease progression/relapse or death from any cause, whichever occurs first. | N/A - End point not assessed | 
| Progression Free Survival (PFS) | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first dose of study medication to first documentation of disease progression/relapse, or to death due to any cause, whichever occurs first. | N/A - End point not assessed | 
| Rate of Transformation to Acute Myeloid Leukemia (AML) | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the rate of transformation to AML after initiation of study therapy. | N/A - End point not assessed | 
| Overall Survival (OS) | Study did not progress to Phase 2. A comparison between the 2 arms (Phase 2) of the time from first dose of study medication to death due to any cause. | N/A - End point not assessed | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibody-Drug Conjugate CD33 Antigen