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

NCT02205333 | Terminated Phase 1 Results

• 1 other identifier: D4981C00001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Advanced Solid Tumors; Aggressive B-cell Lymphomas

Keywords

Advanced Solid tumors; Diffuse Large B-cell Lymphoma; programmed death 1; programmed dealth ligand 1; cytotoxic T-lymphocyte-associated antigen-4; OX40 ligand

Outcome Measures

Primary Outcomes (7)

• Maximum Tolerated Dose (MTD) of MEDI6469

  The MTD was the highest dose within a cohort where no more than 1 out of 6 participants experienced dose-limiting toxicities (DLTs) or the highest protocol-defined dose for each agent in the absence of exceeding the MTD.

  From the first dose of study treatment through 28 days after the first dose (up to 28 days)

• Number of Participants With DLTs

  The DLT was any Grade 3 or higher treatment-related toxicity (including liver transaminase elevation higher than 8×upper limit of normal \[ULN\] or total bilirubin higher than 5×ULN; any \>=Grade 2 pneumonitis that did not resolve to \<=Grade 1 within 3 days) that occurred during the DLT time frame, and excluded the following: Grade 3 fatigue for less than or equal to (\<=) 7 days; Grade 3 endocrinopathy that was managed and the participant was asymptomatic; Grade 3 inflammatory reaction attributed to a local antitumor response that resolved to \<=Grade 1 within 30 days; concurrent vitiligo or alopecia of any grade; Grade 3 infusion-related reaction that resolved within 6 hours; and any more than or equal to (\>=) Grade 3 lymphopenia (unless clinically significant).

  From the first dose of study treatment through 28 days after the first dose (up to 28 days)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs were events present at baseline that worsened in intensity after administration of study treatment or events absent at baseline that emerged after administration of study treatment.

  From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)

• Number of Participants With Treatment-emergent Serious Adverse Events

  A serious adverse event (SAE) was any AE that resulted in death, immediately life threatening, required (or prolonged) inpatient (or existing) hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect in offspring of the participant, or an important medical event that could jeopardize the participant or required medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs were defined as SAEs present at baseline that worsened in intensity after administration of study treatment or SAEs absent at baseline that emerged after administration of study treatment.

  From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)

• Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs

  Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell \[WBC\] count with differential, red blood cell \[RBC\] count, hematocrit, hemoglobin, platelet count, mean corpuscular volume \[MCV\], and mean corpuscular hemoglobin concentration \[MCHC\]); serum chemistry (calcium, chloride, magnesium, creatinine, sodium, blood urea nitrogen \[BUN\], bicarbonate, glucose, aspartate transaminase \[AST\], total bilirubin, C-reactive protein, gamma-glutamyl transpeptidase \[GGT\], lactate dehydrogenase, uric acid, potassium, alanine transaminase \[ALT\], alkaline phosphatase, albumin, total protein, triglycerides, and cholesterol); urinalysis; and coagulation parameters.

  From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)

• Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs

  Vital signs examination included assessment of temperature, blood pressure, pulse rate, and respiratory rate. Physical examination included assessments of head, eyes, ears, nose, throat, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems. The TEAEs related to these vital sign and physical examination abnormalities were reported.

  From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)

• Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs

  Electrocardiogram (ECG) parameters included atrial rate, PR interval, QRS duration, QTC interval, QT interval, and ventricular rate. All 12-lead ECGs performed during the study were obtained in triplicate. The TEAEs related to these ECG evaluation abnormalities were reported.

  From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)

Secondary Outcomes (11)

• Best Overall Response (BOR)

  From study entry until early termination (up to 1 year)

• Objective Response Rate (ORR)

  From study entry until early termination (up to 1 year)

• Disease Control Rate

  From study entry until early termination (up to 1 year)

• Duration of Response (DOR)

  From Study entry until early termination (up to 1 year)

• Progression-free Survival (PFS)

  From Study entry until early termination (up to 1 year)

Study Arms (9)

MEDI6469 6 mg/kg

EXPERIMENTAL

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

Biological: MEDI6469 Monotherapy

MEDI6469 10 mg/kg

EXPERIMENTAL

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

Biological: MEDI6469 Monotherapy

MEDI6469 2 mg/kg+Tremelimumab 3 mg/k

EXPERIMENTAL

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

Biological: MEDI6469 Plus Tremelimumab

MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg

EXPERIMENTAL

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)

Biological: MEDI6469 Plus Tremelimumab

MEDI6469 2 mg/kg+Durvalumab 3 mg/kg

EXPERIMENTAL

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

Biological: MEDI6469 Plus Durvalumab

MEDI6469 2 mg/kg+Durvalumab 10 mg/kg

EXPERIMENTAL

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

Biological: MEDI6469 Plus Durvalumab

MEDI6469 10 mg/kg+Durvalumab 10 mg/kg

EXPERIMENTAL

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

Biological: MEDI6469 Plus Durvalumab

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

EXPERIMENTAL

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

Biological: MEDI6469 plus Rituximab

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

EXPERIMENTAL

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

Biological: MEDI6469 plus Rituximab

Interventions

MEDI6469 Monotherapy BIOLOGICAL

single intravenous (IV) administration of MEDI6469

MEDI6469 10 mg/kg; MEDI6469 6 mg/kg

MEDI6469 Plus Tremelimumab BIOLOGICAL

MEDI6469 in combination with Tremelimumab

MEDI6469 2 mg/kg+Tremelimumab 10 mg/kg; MEDI6469 2 mg/kg+Tremelimumab 3 mg/k

MEDI6469 Plus Durvalumab BIOLOGICAL

MEDI6469 in combination with Durvalumab

MEDI6469 10 mg/kg+Durvalumab 10 mg/kg; MEDI6469 2 mg/kg+Durvalumab 10 mg/kg; MEDI6469 2 mg/kg+Durvalumab 3 mg/kg

MEDI6469 plus Rituximab BIOLOGICAL

MEDI6469 in combination with Rituximab

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

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (13)

Research Site

Scottsdale, Arizona, 85259, United States

Location

Research Site

Sacramento, California, 95817, United States

Location

Research Site

Santa Monica, California, 90404, United States

Location

Research Site

Washington D.C., District of Columbia, 20007, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Chicago, Illinois, 60611, United States

Location

Research Site

Detroit, Michigan, 48202, United States

Location

Research Site

Las Vegas, Nevada, 89169, United States

Location

Research Site

Hackensack, New Jersey, 7601, United States

Location

Research Site

Huntersville, North Carolina, 28078, United States

Location

Research Site

Portland, Oregon, 97213, United States

Location

Research Site

Memphis, Tennessee, 38120, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

tremelimumab; durvalumab; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated early at the Sponsor's discretion.

Results Point of Contact

• Title: Victoria Chiou
• Organization: MedImmune, LLC

chiouv@MedImmune.com

301-398-4330

Study Officials

• MedImmune, LLC

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2014
• First Posted: July 31, 2014
• Study Start: August 13, 2014
• Primary Completion: April 8, 2016
• Study Completion: April 8, 2016
• Last Updated: June 28, 2017
• Results First Posted: May 8, 2017

Record last verified: 2017-06

Locations

US (13)