A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer

Sponsor

Celldex Therapeutics (Industry)

Overall Status

Terminated

CT.gov ID

NCT02543645

Collaborator

Genentech, Inc. (Industry)

Enrollment

Locations

Arm

19.7

Duration (Months)

4.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	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

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

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

Study Start Date :

Oct 1, 2015

Actual Primary Completion Date :

Apr 1, 2017

Actual Study Completion Date :

May 22, 2017

Arms and Interventions

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.

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.

Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California - San Francisco	San Francisco	California	United States	94550
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Duke University Medical Center	Durham	North Carolina	United States	27710