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A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer

Primary Purpose

Carcinoma, Renal Cell, Kidney Diseases, Kidney Neoplasms

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Combination of Varlilumab and Atezolizumab

About this trial

This is an interventional treatment trial for Carcinoma, Renal Cell

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy.
Progressed or intolerant to at least 1 approved prior anticancer regimen.
Measurable (target) disease.
Life expectancy ≥ 12 weeks.
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.
Must have available tumor tissue and consent to biopsy while on study.
Patients with asymptomatic treated CNS metastasis may be enrolled after discussion with the Medical Monitor.
ECOG of 0 or 1.

Exclusion Criteria:

Prior therapy with varlilumab or with an anti-CD27 antibody.
Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 therapy.
Use of any experimental immunotherapy.
Receipt of anti-CTLA-4 targeted therapies or other checkpoint or co-stimulatory therapy within 3 months prior to start of study treatment.
Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned state of study treatment.
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.
Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.
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.
Active, untreated CNS metastases.
Active autoimmune disease or a documented history of autoimmune disease.
Active diverticulitis.
Significant cardiovascular disease including CHF, leptomeningeal disease, poorly controlled hypertension, or an MI within 6 months prior to dosing.
Known alcohol or drug abuse.

Sites / Locations

University of California - San Francisco
Beth Israel Deaconess Medical Center
Memorial Sloan Kettering Cancer Center
Duke University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Varlilumab and Atezolizumab

Arm Description

Outcomes

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02543645

First Posted

August 28, 2015

Last Updated

April 26, 2018

Sponsor

Celldex Therapeutics

Collaborators

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02543645

Brief Title

A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Terminated

Why Stopped

Portfolio re-prioritization

Study Start Date

October 2015 (undefined)

Primary Completion Date

April 2017 (Actual)

Study Completion Date

May 22, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celldex Therapeutics

Collaborators

Genentech, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Varlilumab and Atezolizumab

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Combination of Varlilumab and Atezolizumab

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time Frame

Safety follow-up is 70 days from last study drug dose.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Documented progressive disease based on radiographic, clinical or pathologic assessment during or subsequent to last therapy. Progressed or intolerant to at least 1 approved prior anticancer regimen. Measurable (target) disease. Life expectancy ≥ 12 weeks. 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. Must have available tumor tissue and consent to biopsy while on study. Patients with asymptomatic treated CNS metastasis may be enrolled after discussion with the Medical Monitor. ECOG of 0 or 1. Exclusion Criteria: Prior therapy with varlilumab or with an anti-CD27 antibody. Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 therapy. Use of any experimental immunotherapy. Receipt of anti-CTLA-4 targeted therapies or other checkpoint or co-stimulatory therapy within 3 months prior to start of study treatment. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned state of study treatment. 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. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment. 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. Active, untreated CNS metastases. Active autoimmune disease or a documented history of autoimmune disease. Active diverticulitis. Significant cardiovascular disease including CHF, leptomeningeal disease, poorly controlled hypertension, or an MI within 6 months prior to dosing. Known alcohol or drug abuse.

Facility Information:

Facility Name

University of California - San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94550

Country

United States

Facility Name

Beth Israel Deaconess Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

12. IPD Sharing Statement

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A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer

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