Summary

at UCSD UC Davis
study started
estimated completion:
Lyudmila A. Bazhenova (ucsd)

Description

Summary

This phase II trial studies how well durvalumab and tremelimumab works in treating patients with stage IV lung cancer that has come back after previous treatment. Monoclonal antibodies, such as durvalumab and tremelimumab, may interfere with the ability of tumor cells to grow and spread.

Official Title

A Phase II Study of MEDI4736 (Durvalumab) Plus Tremelimumab as Therapy for Patients With Previously Treated Anti-PD-1/PD-L1 Resistant Stage IV Squamous Cell Lung Cancer (Lung-Map Non-Match Sub-Study)

Details

PRIMARY OBJECTIVES:

  1. To evaluate the objective response rate (confirmed and unconfirmed, complete and partial) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 among patients treated with durvalumab (MEDI4736) plus tremelimumab.

SECONDARY OBJECTIVES:

  1. To estimate the duration of response (DoR) among patients who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by RECIST 1.1.

II. To estimate the duration of response (DoR) per immune-related response criteria among patients who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by RECIST 1.1.

III. To evaluate overall survival (OS) among patients treated with durvalumab (MEDI4736) plus tremelimumab.

IV. To evaluate investigator-assessed progression-free survival (IA-PFS) among patients treated with durvalumab (MEDI4736) plus tremelimumab.

  1. To evaluate IA-PFS assessed by immune-related response criteria (irRC-IA-PFS) among patients treated with durvalumab (MEDI4736) plus tremelimumab.

VI. To evaluate the frequency and severity of toxicities associated with durvalumab (MEDI4736) plus tremelimumab.

TERTIARY OBJECTIVES:

  1. To explore the association of potential predictive markers identified in S1400A, with response and progression-free survival (PFS).

II. To explore the association of PD-L1 expression status with response and PFS.

III. To contribute to an ongoing serum and tumor bank in S1400.

OUTLINE:

Patients receive tremelimumab intravenously (IV) over 60 minutes on day 1 for courses 1-4 and durvalumab IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years, and then at the end of year 3.

Keywords

Recurrent Squamous Cell Lung Carcinoma Stage IV Squamous Cell Lung Carcinoma AJCC v7 Carcinoma Lung Neoplasms Antibodies, Monoclonal Immunoglobulins Immunoglobulin G Tremelimumab Durvalumab Laboratory Biomarker Analysis

Eligibility

Inclusion Criteria:

  • Patients must have been assigned to S1400F
  • Patients must have progressed during or after prior platinum-based chemotherapy;patients whose only prior platinum-based chemotherapy regimen was for stage I-III disease (i.e. patient has not received any platinum-based chemotherapy for stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy;patients must have experienced disease progression during or after prior anti-PD-1 or anti-PD-L1 antibody monotherapy as their most recent line of treatment; prior PD-1/PD-L1 combination therapy is not permitted
  • Prior exposure to CTLA-4 inhibitors (ipilimumab and tremelimumab) is not permitted;prior exposure to the following is allowed: attenuated vaccines, anti-EGFR agents, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
  • Patients must not have received nitrosoureas or mitomycin-C within 42 days prior to sub-study registration
  • Patients must not have any prior documented autoimmune or inflammatory disease(including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome) within 3 years prior to sub-study registration; patients with vitiligo,immune-mediated alopecia, Grave?s disease, or psoriasis requiring systemic treatment within the past 2 years are not eligible; patients with hypothyroidism (e.g. post Hashimoto syndrome) who are stable on hormone replacement therapy are eligible
  • Patients must not have any history of primary immunodeficiency
  • Patients must not have received any immunosuppressive medication within 28 days prior to sub-study registration and must not be planning to receive these medications while on protocol therapy; systemic corticosteroids must be stopped at least 24 hours prior to sub-study registration; however, intranasal and inhaled corticosteroids are allowed at any time before and during protocol therapy
  • Patients must not have experienced a grade 3 or worse immune-related adverse event(irAE) (except asymptomatic nonbullous/nonexfoliative rash) or any unresolved irAE grade 2, nor have experienced a toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1 immunotherapy
  • Patients must not have any history of organ transplant that requires use of immunosuppressives
  • Patients must not have any known allergy or reaction to any component of the durvalumab (MEDI4736) and/or tremelimumab formulation
  • Patients must not have clinical signs or symptoms of active tuberculosis infection
  • Patients must not have received a live attenuated vaccination within 28 days prior to sub-study registration
  • Patients must not have known human immunodeficiency virus (HIV), or a known positive test for hepatitis B virus surface antigen (HBV sAg), or hepatitis C virus ribonucleic acid (HCV antibody) indicating current acute or chronic infection; patients with a positive hepatitis C antibody with a negative viral load are allowed
  • Patients must have a thyroid-stimulating hormone (TSH) with reflex free T3/free T4 (if TSH is out of normal range) and electrocardiogram (EKG) obtained within 7 days prior to sub-study registration
  • Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens

Locations

  • UC San Diego Moores Cancer Center accepting new patients
    La Jolla California 92093 United States
  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento California 95817 United States
  • California Pacific Medical Center-Pacific Campus accepting new patients
    San Francisco California 94115 United States
  • Kaiser Permanente-San Francisco accepting new patients
    San Francisco California 94115 United States
  • Sutter Davis Hospital accepting new patients
    Davis California 95616 United States
  • Kaiser Permanente-Cadillac accepting new patients
    Los Angeles California 90034 United States
  • Kaiser Permanente-Irvine accepting new patients
    Irvine California 92618 United States
  • Kaiser Permanente-South San Francisco accepting new patients
    South San Francisco California 94080 United States
  • Kaiser Permanente accepting new patients
    Fresno California 93720 United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center accepting new patients
    Burbank California 91505 United States

Lead Scientist

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Southwest Oncology Group
ID
NCT03373760
Phase
Phase 2
Study Type
Interventional
Last Updated