A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer

Phase 1

Terminated

• Conditions: Clear-cell Metastatic Renal Cell Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms; Urologic Neoplasms; Head and Neck Cancer; Urologic Diseases; Triple Negative Breast Cancer; Non-small Cell Lung Cancer; Urogenital Neoplasms; Neoplasms by Histologic Type
• Interventions: Drug: Combination of Varlilumab and Atezolizumab

• Registration Number: NCT02543645
• Lead Sponsor: Celldex Therapeutics

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.

Study Timeline

• Study First Submitted: 2015-08-28
• Study First Submitted QC: 2015-09-04
• Study First Posted: 2015-09-07
• Study Start: 2015-10
• Primary Completion: 2017-04
• Study Completion: 2017-05-22
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-26
• Last Update Posted: 2018-04-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Varlilumab and Atezolizumab	Combination of Varlilumab and Atezolizumab	-

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (4)

University of California - San Francisco; 🇺🇸 San Francisco, California, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States