Clinical Trials /

A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer

NCT02543645

Description:

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

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: CDX1127-06
  • NCT ID: NCT02543645

Conditions

  • 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

Interventions

DrugSynonymsArms
Combination of Varlilumab and AtezolizumabVarlilumab and Atezolizumab

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Varlilumab and AtezolizumabExperimental
  • Combination of Varlilumab and Atezolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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 Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Celldex Therapeutics

Last Updated

June 16, 2017