A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer

April 26, 2018 updated by: Celldex Therapeutics

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

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).*

*Note: This Study was terminated prior to initiation of Phase II

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

*Note: This Study was terminated prior to initiation of Phase II.

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94550
        • University of California - San Francisco
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.
  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Safety follow-up is 70 days from last study drug dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celldex Therapeutics

Collaborators

Genentech, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Actual)

April 1, 2017

Study Completion (Actual)

May 22, 2017

Study Registration Dates

First Submitted

August 28, 2015

First Submitted That Met QC Criteria

September 4, 2015

First Posted (Estimate)

September 7, 2015

Study Record Updates

Last Update Posted (Actual)

April 30, 2018

Last Update Submitted That Met QC Criteria

April 26, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDX1127-06

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Melanoma

Clinical Trials on Combination of Varlilumab and Atezolizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Croatia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe