A Phase 1b/2 Safety and Tolerability Study of MEDI6469 in Combination With Therapeutic Immune Agents or Monoclonal Antibodies

MedImmune

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Advanced Solid Tumors; Aggressive B-cell Lymphomas

Treatments: Biological: MEDI6469 Plus Durvalumab; Biological: MEDI6469 Plus Tremelimumab; Biological: MEDI6469 Monotherapy; Biological: MEDI6469 plus Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02205333

D4981C00001

Details and patient eligibility

About

The main purpose of this study is to determine the best dose of MEDI6469 that is safe and tolerable when given as monotherapy and in combination with tremelimumab, MEDI4736 (durvalumab), or rituximab in participants with either advanced solid tumors or diffuse large B-cell lymphoma (DLBCL). Tremelimumab and MEDI4736 (durvalumab) will be tested with MEDI6469 in a set of participants with advanced solid tumors while rituximab will be tested with MEDI6469 in participants with DLBCL. MEDI6469 will be tested as monotherapy in participants with advanced solid tumors.

Enrollment: 48 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults >/= 18 years old
• Histologically or cytologically confirmed advanced solid tumors that are refractory to standard therapy or for which no standard therapy exists (Monotherapy and in Cohorts A and B)
• At least one lesion measurable by RECIST not previously irradiated (Monotherapy and in Cohorts A and B)
• Histologically confirmed DLBCL(Cohort C)
• Adequate organ and marrow function
• ECOG performance status of 0 or 1
• Willingness to provide consent for biopsy samples

Exclusion criteria

• Prior exposure to immunotherapy (either as a single agent or in combination) including but not limited to CD137 or OX40 agonists, anti-CTLA-4, anti-PD-1, or anti-PD-L1, anti-PD-L2 antibody or pathway-targeting agents
• History of organ transplant that requires use of immunosuppressives
• History of primary immunodeficiency or tuberculosis
• Active or prior documented autoimmune disease within the past 3 years
• Active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months
• Major surgical procedure within 30 days prior to the first dose of investigational product or still recovering from prior surgery
• Women who are pregnant or lactating

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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48 participants in 9 patient groups

MEDI6469 6 mg/kg

Experimental group

Description:

Participants received MEDI6469 6 milligram/kilogram (mg/kg) as a single intravenous (IV) administration on Day 1

Treatment:

Biological: MEDI6469 Monotherapy

MEDI6469 10 mg/kg

Experimental group

Description:

Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1

Treatment:

Biological: MEDI6469 Monotherapy

MEDI6469 2 mg/kg+Tremelimumab 3 mg/k

Experimental group

Description:

Participants received MEDI6469 2 mg/kg as a single IV administration on Day 1 plus tremelimumab 3 mg/kg as IV administration on Day 1 then every 4 weeks (Q4W) for 6 doses, after which every 12 weeks (Q12W) for 2 doses or until PD

Treatment:

Biological: MEDI6469 Plus Tremelimumab

MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg

Experimental group

Description:

Participants received MEDI6469 2 mg/kg as a single IV administration on Day 1 plus tremelimumab 10 mg/kg as IV administration on Day 1 then Q4W for 6 doses after which Q12W for 2 doses or until progression of disease (PD)

Treatment:

Biological: MEDI6469 Plus Tremelimumab

MEDI6469 2 mg/kg+Durvalumab 3 mg/kg

Experimental group

Description:

Participants received MEDI6469 2 mg/kg as a single IV administration on Day 1 plus durvalumab 3 mg/kg as IV administration on Day 1 then every 2 weeks (Q2W) for 12 months or until PD

Treatment:

Biological: MEDI6469 Plus Durvalumab

MEDI6469 2 mg/kg+Durvalumab 10 mg/kg

Experimental group

Description:

Participants received MEDI6469 2 mg/kg as a single IV administration on Day 1 plus durvalumab 10 mg/kg as IV administration on Day 1, then Q2W for 12 months or until PD

Treatment:

Biological: MEDI6469 Plus Durvalumab

MEDI6469 10 mg/kg+Durvalumab 10 mg/kg

Experimental group

Description:

Participants received MEDI6469 10 mg/kg as a single IV administration on Day 1 plus durvalumab 10 mg/kg as IV administration on Day 1, then Q2W for 12 months or until PD

Treatment:

Biological: MEDI6469 Plus Durvalumab

MEDI6469 2 mg/kg+Rituximab 375 mg/m^2

Experimental group

Description:

Participants received MEDI6469 2 mg/kg as a repeat IV administration on Day 3 then Q4W for 11 doses, or until confirmed complete response (CR) plus 1 cycle, or PD plus rituximab 375 mg/m\^2 as IV administration on Days 1, 8, and 29; then Q4W for 10 doses, or until confirmed CR plus 1 cycle, or PD

Treatment:

Biological: MEDI6469 plus Rituximab

MEDI6469 10 mg/kg+Rituximab 375 mg/m^2

Experimental group

Description:

Participants received MEDI6469 10 mg/kg as a repeat IV administration on Day 3 then Q4W for 11 doses, or until confirmed CR plus 1 cycle, or PD plus rituximab 375 mg/m2 as IV administration on Days 1, 8, and 29; then Q4W for 10 doses, or until confirmed CR plus 1 cycle, or PD

Treatment:

Biological: MEDI6469 plus Rituximab