A Clinical Trial of Durvalumab (MEDI4736) as 1st Line Therapy in Advanced Non-small Cell Lung Cancer Patients

A Phase II Clinical Trial Evaluating the Safety and Efficacy of Durvalumab (MEDI4736) as 1st Line Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Patients With Eastern Cooperative Oncology Group (ECOG) Performance Status of 2

This is a single-arm phase II clinical trial evaluating the safety and efficacy of the PD-L1 inhibitor durvalumab as first-line therapy in 47 patients with advanced NSCLC and ECOG Performance Status 2 (PS2).

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer NSCLC
• Intervention / Treatment: Drug: durvalumab

Detailed Description

Durvalumab will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Durvalumab will be administered at 1500 mg (fixed dose) every 4 weeks until disease progression, death, unacceptable toxicity or withdrawal of consent for a maximum of 12 months of therapy.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center - UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent
• Patients must have histologically or cytologically confirmed Stage IIIB or IV (American Joint Committee on Cancer, 7th edition; AJCC 7) non-small cell lung cancer.
• Patients must have measurable disease.
• Patients must have not have received any prior therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) for the treatment of stage IV NSCLC.
• Age ≥ 18 years at time of study entry.
• ECOG performance status of 2.
• Life expectancy of greater than 12 weeks.
• Tissue available (archived or fresh tumor biopsy) for the PD-L1 assay.

• Patients must have normal organ and marrow function as defined below:

  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
  • Hemoglobin ≥ 9.0 g/dL
  • Platelet count ≥ 100 x 10^9/L (>100,000 per mm^3)
  • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN unless liver metastases are present, in which case it must be ≤ 5x ULN Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula
• Female subjects must either be of non-reproductive potential OR must have a negative serum pregnancy test upon study entry.
• The effects of durvalumab on the developing human fetus are unknown. For this reason and because immunomodulatory agents are potentially teratogenic, sexually active women of child-bearing potential and men must agree to use adequate contraception (2 methods of effective contraception from screening) from screening, for the duration of study participation, and for at least 90 days following the last infusion of durvalumab.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

• Involvement in the planning and/or conduct of the study; previous enrollment in the present study.
• Participation in another clinical study with an investigational product for cancer during the last 12 months.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
• Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids in excess of prednisone 10 mg/d or equivalent.
• Sensitizing mutations in EGFR or rearrangements in ALK or ROS1.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab.
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids . Patients may be on systemic corticosteroids provided the dose does not exceed prednisone 10 mg/d or equivalent for 1 week prior to study drug administration.
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of allogeneic organ transplant.
• Uncontrolled intercurrent illness.
• Known history of previous clinical diagnosis of tuberculosis.
• History of leptomeningeal carcinomatosis.
• Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
• Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
• Subjects with uncontrolled seizures.
• Pregnant women; breastfeeding should be discontinued.
• Prior history of radiation pneumonitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: durvalumab; 1500 mg of durvalumab will be administered intravenously (IV) on day 1 of every 28 day cycle.	Drug: durvalumab; A human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody directed against programmed cell death ligand 1 (PD-L1); Other Names: MEDI4736

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Median length of time from the start of treatment from start of treatment to death from any cause.	Up to 30 months
Overall Survival (OS12)	Number of patients alive at 12 months post start of treatment.	At 12 months
Overall Survival (OS24)	Number of patients alive at 24 months post start of treatment.	At 24 months
Treatment-related Adverse Events ≥ Grade 3	Number of participants with ≥ Grade 3 adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 that are at least possibly related to study treatment.	Up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Median duration of time from start of treatment to time of progression or death, whichever occurs first. Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions:Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	Up to 30 months
Progression-Free Survival (PFS) at 12 Months	Number of patients without progressive disease or death at 12 months from start of treatment. Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	At 12 months
Progression-Free Survival (PFS) at 24 Months	Number of patients without progressive disease or death at 24 months from start of treatment Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions:Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	At 24 months
Progression-Free Survival (PFS) by PD-L1 Expression at 12 Months	Number of patients of know PD-L1 status without progressive disease or death at 12 months from start of treatment. Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	At 12 months
Progression-Free Survival (PFS) by PD-L1 Expression Status at 24 Months	Number of patients of know PD-L1 status without progressive disease or death at 24 months from start of treatment Per RECIST v1.0 Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions:Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	At 24 months
Overall Survival by PD-L1 Expression Status at 12 Months	Number of patients with know PD-L1 status that are alive at 12 months post start of treatment.	At 12 months
Overall Survival by PD-L1 Expression Status at 24 Months	Number of patients with know PD-L1 status that are alive at 24 months post start of treatment.	At 24 months
Overall Response Rate (ORR)	Percentage of patients with a Best Response of Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). Per RECIST v1.0, for target lesions: PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither PR nor PD (target lesions); persistence of 1 or more non-target lesions and/or the maintenance of tumor marker levels above normal limits. PD: at least a 20% increase in sum of diameters (target lesions), taking as reference the smallest sum on study (includes baseline sum if smallest on study). In addition to relative increase of 20%, sum must demonstrate absolute increase of at least 5 mm. (includes appearance of one or more new lesions) Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	Up to 30 months
Overall Response Rate (ORR) in Patients With PD-L1 Expression Status = 0	Percentage of patients with PD-L1 expression status = 0, with a Best Response of Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). Per RECIST v1.0 (target lesions): PR: ≥30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither PR nor PD (target lesions); persistence of 1 or more non-target lesions and/or the maintenance of tumor marker levels above normal limits. PD: ≥20% increase in sum of diameters (target lesions), taking as reference the smallest sum on study (includes baseline sum if smallest on study). In addition to relative increase of 20%, sum must demonstrate absolute increase of at least 5 mm. (includes appearance of one or more new lesions) ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	Up to 30 months
Overall Response Rate (ORR) in Patients With PD-L1 Expression Status = 0%<PD-L1<50%.	Percentage of patients with PD-L1 expression status=0%<PD-L1<50%, with a Best Response of Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). Per RECIST v1.0 (target lesions): PR: ≥30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither PR nor PD (target lesions); persistence of 1 or more non-target lesions and/or the maintenance of tumor marker levels above normal limits. PD: ≥20% increase in sum of diameters (target lesions), taking as reference the smallest sum on study (includes baseline sum if smallest on study). In addition to relative increase of 20%, sum must demonstrate absolute increase of at least 5 mm. (includes appearance of one or more new lesions) ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	Up to 30 months
Overall Response Rate (ORR) in Patients With PD-L1 Expression Status ≥50%	Percentage of patients with PD-L1 expression status ≥50%, with a Best Response of Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). Per RECIST v1.0 (target lesions): PR: ≥30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither PR nor PD (target lesions); persistence of 1 or more non-target lesions and/or the maintenance of tumor marker levels above normal limits. PD: ≥20% increase in sum of diameters (target lesions), taking as reference the smallest sum on study (includes baseline sum if smallest on study). In addition to relative increase of 20%, sum must demonstrate absolute increase of at least 5 mm. (includes appearance of one or more new lesions) ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	Up to 30 months
Health Related Quality of Life (HRQL) - FACT-G	Patient self-administered 27-item questionnaire that measures health state in cancer patients in prior 7 days, including physical, social, emotional, and functional well-being. Scoring: Five-point scale: 0 (not at all) to 4 (very much). Total score is from 0-108. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.	At baseline
Health Related Quality of Life (HRQL) - FACT-G	Patient self-administered 27-item questionnaire that measures health state in cancer patients in prior 7 days, including physical, social, emotional, and functional well-being. Scoring: Five-point scale: 0 (not at all) to 4 (very much). Total score is from 0-108. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.	Within first two treatment cycles, up to 56 days
Health Related Quality of Life (HRQL) - FACT-G	Patient self-administered 27-item questionnaire that measures health state in cancer patients in prior 7 days, including physical, social, emotional, and functional well-being. Scoring: Five-point scale: 0 (not at all) to 4 (very much). Total score is from 0-108. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.	At 6 months
Health Related Quality of Life (HRQL) - FACT-G	Patient self-administered 27-item questionnaire that measures health state in cancer patients in prior 7 days, including physical, social, emotional, and functional well-being. Scoring: Five-point scale: 0 (not at all) to 4 (very much). Total score is from 0-108. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.	At 12 months
FACT Lung Cancer Subscale (LCS)	The FACT-LCS is the lung cancer subscale of the FACT-L. LCS includes the average symptom burden index (ASBI; based on 5 symptoms: anorexia, fatigue, cough, dyspnea, hemoptysis, and pain) and the 3-item global index (2-IGI; symptom distress, interference with activities, and health-related quality of life). Scoring: Five-point scale: 0 (not at all) to 4 (very much). Total score is from 0-28. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.	At baseline
FACT Lung Cancer Subscale (LCS)	The FACT-LCS is the lung cancer subscale of the FACT-L. LCS includes the average symptom burden index (ASBI; based on 5 symptoms: anorexia, fatigue, cough, dyspnea, hemoptysis, and pain) and the 3-item global index (2-IGI; symptom distress, interference with activities, and health-related quality of life). Scoring: Five-point scale: 0 (not at all) to 4 (very much). Total score is from 0-28. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.	Within first two treatment cycles, up to 56 days
FACT Lung Cancer Subscale (LCS)	The FACT-LCS is the lung cancer subscale of the FACT-L. LCS includes the average symptom burden index (ASBI; based on 5 symptoms: anorexia, fatigue, cough, dyspnea, hemoptysis, and pain) and the 3-item global index (2-IGI; symptom distress, interference with activities, and health-related quality of life). Scoring: Five-point scale: 0 (not at all) to 4 (very much). Total score is from 0-28. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.	At 6 months
FACT Lung Cancer Subscale (LCS)	The FACT-LCS is the lung cancer subscale of the FACT-L. LCS includes the average symptom burden index (ASBI; based on 5 symptoms: anorexia, fatigue, cough, dyspnea, hemoptysis, and pain) and the 3-item global index (2-IGI; symptom distress, interference with activities, and health-related quality of life). Scoring: Five-point scale: 0 (not at all) to 4 (very much). Total score is from 0-28. Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.	At 12 months

Collaborators and Investigators

• Sponsor: Academic Thoracic Oncology Medical Investigators Consortium
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Liza Villaruz, MD, University of Pittsburgh Cancer Institute, Department of Hematology Oncology

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2017
• Primary Completion (Actual): June 4, 2022
• Study Completion (Actual): June 4, 2022

Study Registration Dates

• First Submitted: July 22, 2016
• First Submitted That Met QC Criteria: August 22, 2016
• First Posted (Estimated): August 25, 2016

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: PD-L1 (programmed cell death ligand 1)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: 16-054

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article after deidentification, in addition to the Study Protocol, will be available immediately following publication. Investigators whose proposed use of the data has been approved by an independent review committee may access the data to achieve aims in the approved proposal. Proposals should be directed to villaruzl@upmc.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years after publication.
• IPD Sharing Time Frame: Data are available for 5 years after publication.
• IPD Sharing Access Criteria: Proposals should be directed to villaruzl@upmc.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No