We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer

This study has been terminated.
(Portfolio re-prioritization)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02543645
First Posted: September 7, 2015
Last Update Posted: June 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Celldex Therapeutics
  Purpose
This is a study to determine the clinical benefit (how well the drug works), safety and tolerability of combining varlilumab and atezolizumab. Phase l of the study will enroll patients with a number of tumor types; Phase ll will enroll only patients with renal cell carcinoma (RCC).

Condition Intervention Phase
Carcinoma, Renal Cell Kidney Diseases Kidney Neoplasms Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Neoplasms by Histologic Type Neoplasms Clear-cell Metastatic Renal Cell Carcinoma Melanoma Triple Negative Breast Cancer Bladder Cancer Head and Neck Cancer Non-small Cell Lung Cancer Drug: Combination of Varlilumab and Atezolizumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase l/ll, Open Label, Dose-escalation Study of Varlilumab (CDX-1127) in Combination With Atezolizumab (MPDL3280A, Anti-PD-L1) in Patients With Advanced Cancer

Resource links provided by NLM:


Further study details as provided by Celldex Therapeutics:

Primary Outcome Measures:
  • Phase l: Safety and tolerability of varlilumab in combination with atezolizumab as measured by incidence of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities and laboratory test abnormalities. [ Time Frame: Safety follow-up is 70 days from last study drug dose. ]
  • Phase ll: Objective Response Rate [ Time Frame: Evaluated every 12 weeks until treatment is discontinued or disease progression, up to 5 years. ]
    The Objective Response Rate is defined as the proportion of patients with Stage lll or IV renal cell carcinoma (RCC) who achieve radiographic partial or complete response (PR or CR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 guideline.


Enrollment: 18
Study Start Date: October 2015
Study Completion Date: May 22, 2017
Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Varlilumab and Atezolizumab Drug: Combination of Varlilumab and Atezolizumab

Treatment cycles are 12 weeks each with varlilumab and atezolizumab administered every 3 weeks. During the treatment phase of the study, eligible patients will receive varlilumab for up to 3 cycles (with a 4th cycle possible following discussion with the Medical Monitor). There is no limit on the number of cycles of atezolizumab. Patients may be discontinued from receiving study treatment (atezolizumab or varlilumab) based on the results of disease assessments or if experiencing side effects that make study therapy intolerable.

Phase l Dose: The planned dose of varlilumab will be dependent on the cohort assigned at enrollment. Varlilumab doses are 0.3 mg/kg, 1 mg/kg, or 3 mg/kg. The dose of atezolizumab is 1200 mg.

Phase ll Dose: The planned varlilumab dose will be established from the outcome of the Phase l portion of the study. Patients will receive atezolizumab at a dose of 1200 mg.


Detailed Description:

Varlilumab is a fully human monoclonal antibody that binds to a molecule called CD27 found on certain immune cells and may act to promote anti-tumor effects.

Atezolizumab is an engineered anti-PD-L1 antibody.

This study will evaluate the safety, tolerability and efficacy of the anti-CD27 antibody varlilumab in combination with atezolizumab.

Eligible patients that enroll in the dose escalation portion of the study will be assigned to one of three dose levels of varlilumab in combination with 1200 mg of atezolizumab. The first phase of the study will enroll up to 18 patients and test the safety profile of the combination of varlilumab and atezolizumab in patients with various tumor types and determine which dose of varlilumab will be studied in Phase ll of the study which will enroll only patients with RCC.

During Phase ll, up to 37 patients will be enrolled and receive the recommended Phase ll dose of varlilumab in combination with atezolizumab 1200 mg.

All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Unresectable stage lll or IV, histologically confirmed diagnosis of one of the following solid tumors:

    • Phase l: Melanoma, RCC, triple negative breast cancer, bladder cancer, head and neck cancer or non-small cell lung cancer.
    • Phase ll: RCC.
  2. Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.
  3. Progressed or intolerant to at least 1 approved prior anticancer regimen.
  4. Measurable (target) disease.
  5. Life expectancy ≥ 12 weeks.
  6. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 90 days following last treatment dose.
  7. Must have available tumor tissue and consent to biopsy while on study.
  8. Patients with asymptomatic treated CNS metastasis may be enrolled after discussion with the Medical Monitor.
  9. ECOG of 0 or 1.

Exclusion Criteria:

  1. Prior therapy with varlilumab or with an anti-CD27 antibody.
  2. Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 therapy.
  3. Use of any experimental immunotherapy.
  4. Receipt of anti-CTLA-4 targeted therapies or other checkpoint or co-stimulatory therapy within 3 months prior to start of study treatment.
  5. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned state of study treatment.
  6. Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of study treatment.
  7. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.
  8. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.
  9. Active, untreated CNS metastases.
  10. Active autoimmune disease or a documented history of autoimmune disease.
  11. Active diverticulitis.
  12. Significant cardiovascular disease including CHF, leptomeningeal disease, poorly controlled hypertension, or an MI within 6 months prior to dosing.
  13. Known alcohol or drug abuse.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02543645


Locations
United States, California
University of California - San Francisco
San Francisco, California, United States, 94550
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Celldex Therapeutics
Genentech, Inc.
  More Information

Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT02543645     History of Changes
Other Study ID Numbers: CDX1127-06
First Submitted: August 28, 2015
First Posted: September 7, 2015
Last Update Posted: June 19, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Carcinoma, Non-Small-Cell Lung
Kidney Diseases
Head and Neck Neoplasms
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Triple Negative Breast Neoplasms
Kidney Neoplasms
Urologic Diseases
Neoplasms by Histologic Type
Urogenital Neoplasms
Urologic Neoplasms
Neoplasms, Glandular and Epithelial
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Urinary Bladder Diseases
Adenocarcinoma
Breast Neoplasms
Breast Diseases
Skin Diseases
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents