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The purpose of this study is to evaluate the safety, tolerability, and efficacy of MEDI4736 (durvalumab) alone and in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory dIffuse large B-cell lymphoma.
This is a multicenter, open-label, dose-escalation and dose-expansion study of MEDI4736 (durvalumab) as monotherapy or in combination with either tremelimumab or AZD9150. The objectives are to describe any dose-limiting toxicities, determine the maximum tolerated dose, and evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics of MEDI4736 as monotherapy or in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory diffuse large B-cell lymphoma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MEDI4736 | Experimental |
| |
| MEDI4736 and tremelimumab | Experimental |
| |
| MEDI4736 and AZD9150 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MEDI4736 | Drug | MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events | Screening through 90 days after the last dose of study medication | |
| Number of subjects experiencing dose-limiting toxicities | Changes from baseline in laboratory parameters, vital signs, and ECGs | First dose of study medications through 28 days after the administration of MEDI4736 or MEDI4736 and tremelimumab, 35 days after administration of MEDI4736 and AZD9150 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects who develop anti-drug antibodies (ADA) | Screening through 90 days after last dose of study medication | |
| Time to Response | Screening though 3 years after the last subject receives the first dose of study medication |
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Inclusion Criteria:
Exclusion Criteria:
3. Active or prior documented autoimmune or inflammatory disease within 3 years, with some exceptions 4. Concurrent or prior conventional or investigational anticancer therapy, within 28 days prior to the first dose of study medication(s)
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| Name | Affiliation | Role |
|---|---|---|
| MedImmune LLC | MedImmune LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | La Jolla | California | 92093 | United States | ||
| Research Site |
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| tremelimumab | Drug | Tremelimumab is an anti-CTLA4 monoclonal antibody (MAb) administered via intravenous infusion |
|
| AZD9150 | Drug | AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion |
|
| Duration of Response | Screening though 3 years after the last subject receives the first dose of study medication |
| Progression Free survival | Screening though 3 years after the last subject receives the first dose of study medication |
| Time to progression | Screening though 3 years after the last subject receives the first dose of study medication |
| Event free survival | Screening though 3 years after the last subject receives the first dose of study medication |
| Overall survival | Screening though 3 years after the last subject receives the first dose of study medication |
| MEDI4736 Maximum Plasma Concentration (Cmax) | Measured at defined study visits from time of first dose through end of treatment |
| Tremelimumab Maximum Plasma Concentration (Cmax) | Measured at defined study visits from time of first dose through end of treatment |
| AZD9150 Maximum Plasma Concentration (Cmax) | Measured at defined study visits from time of first dose through end of treatment |
| MEDI4736 Minimum Plasma Concentration (Cmin) | Measured at defined study visits from time of first dose through end of treatment |
| Tremelimumab Minimum Plasma Concentration (Cmin) | Measured at defined study visits from time of first dose through end of treatment |
| AZD9150 Minimum Plasma Concentration (Cmin) | Measured at defined study visits from time of first dose through end of treatment |
| Individual MEDI4736 Concentrations | Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months) |
| Individual tremelimumab Concentrations | Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months) |
| Individual AZD9150 Concentrations | Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months) |
| Change from baseline of STAT3 RNA (signal transducer and activator of transcription) | Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months) |
| Baseline PD-L1 protein expression within the tumor | Measured on tumor samples provided at screening |
| Baltimore |
| Maryland |
| 21201 |
| United States |
| Research Site | Albuquerque | New Mexico | 87131 | United States |
| Research Site | Durham | North Carolina | 27710 | United States |
| Research Site | Charleston | South Carolina | 29425 | United States |
| Research Site | Dallas | Texas | 75390 | United States |
| Research Site | Houston | Texas | 77030 | United States |
| Research Site | Milwaukee | Wisconsin | 53226 | United States |
| Research Site | Marseille | 13273 | France |
| Research Site | Villejuif | 94805 | France |
| Research Site | Dublin | Ireland |
| Research Site | Galway | Ireland |
| Research Site | Leicester | LE1 5WW | United Kingdom |
| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000613593 | durvalumab |
| C520704 | tremelimumab |
| C000610954 | danvatirsen |
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