Atezolizumab Immunotherapy in Patients With Advanced NSCLC

NCT03102242 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AFT-16
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 13

Brief Summary

Phase II trial of induction immunotherapy with atezolizumab for patients with unresectable stage IIIA and IIIB NSCLC eligible for chemoradiotherapy with curative intent.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate (DCR) After 12 Weeks Induction

  The primary objective of this single arm phase II trial is to determine whether neoadjuvant and adjuvant anti-PD-L1 therapy bracketing standard chemoradiation therapy and consolidation therapy is worthy of further investigation. The primary endpoint will be the disease control rate (DCR) after 12 weeks induction immunotherapy.

  12 weeks

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  12 weeks

• Median PFS

  38.3 months

• Progression Free Survival (PFS) at 12 and 24 Months

  12 and 24 Months

• Median OS

  38.3 Months

• Overall Survival at 12 and 24 Months

  12 and 24 Months

Study Arms (1)

Treatment

EXPERIMENTAL

Induction immunotherapy: atezolizumab 1200 mg IV q 21 days x 4 cycles. Restaging after cycle 2 and cycle 4 induction: patients with progression of disease (PD) at the post-cycle 2 assessment will stop atezolizumab and go immediately to chemoradiotherapy if still stage III and eligible for curative intent therapy. Chemoradiotherapy: carboplatin AUC = 2 + paclitaxel 50 mg/m2 IV weekly x 6 weeks concurrent with radiation to a total dose of 60 Gy given in 2 Gy fractions daily M-F x 30 fractions Consolidation chemotherapy: Carboplatin AUC = 6 + paclitaxel 200 mg/m2 IV q 21 days x 2 cycles beginning 3-5 weeks after completion of radiation. Adjuvant immunotherapy: atezolizumab 1200 mg IV q 21 days to complete one year of therapy (from start of induction).

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Single arm phase II trial of induction immunotherapy with anti-PD-L1 for patients with unresectable stage III NSCLC and PS 0-1.

Treatment

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed stage IIIA/B NSCLC, PS 0-1
• No active autoimmune disease or uncontrolled infection, normal bone marrow, renal, hepatic function, FEV1 \> 1.2L, no significant underlying heart or lung disease
• Pathologically proven diagnosis of NSCLC
• Measurable Stage IIIA or IIIB disease
• Tissue available for PD-L1 testing and for correlative science testing
• Patients must be considered unresectable or inoperable. Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met:
• No prior chemotherapy or radiation for this lung cancer.
• Prior curative-intent surgery at least 3 months prior to the nodal recurrence.
• Stage III A or B disease with minimum diagnostic evaluation within 6 weeks to include:
• History/physical examination
• Contrast enhanced CT of the chest and upper abdomen
• MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated)
• PET/CT
• If pleural fluid is visible on CT scan thoracentesis to exclude malignancy should be obtained. Patients with effusions that are too small to tap are eligible.
• Patients must be at least 4 weeks from major surgery and must be fully recovered

You may not qualify if:

• Active autoimmune disease
• Greater than minimal, exudative, or cytologically positive pleural effusions
• Involved contralateral hilar nodes
• % weight loss within the past month
• Known EGFR exon 19 or 21 mutation or ALK rearrangement
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the breast, localized prostate cancer, carcinoma in situ of the oral cavity, or cervix are all permissible.
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable.
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
• Prior severe infusion reaction to a monoclonal antibody
• Severe, active co-morbidity, defined as follows:
• Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within the last 6 months, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration or within 2 weeks of cycle 1 day 1.
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, HIV testing is required for entry into this protocol due to the immunologic basis for induction treatment.

Sponsors & Collaborators

• Alliance Foundation Trials, LLC.: lead

Study Sites (13)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

UCSD Moores Cancer Center

La Jolla, California, 92037, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

EMMC Cancer Care

Brewer, Maine, 04412, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

Metro MN Community Oncology Research Consortium

Minneapolis, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Ohio State University James Cancer Center

Columbus, Ohio, 43210, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

Prisma Health Greenville Memorial Hospital

Greenville, South Carolina, 29605, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Related Publications (8)

• Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015 Mar;16(3):257-65. doi: 10.1016/S1470-2045(15)70054-9. Epub 2015 Feb 20.

  PMID: 25704439 BACKGROUND

• Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

  PMID: 26028407 BACKGROUND

• Reck M, Paz-Ares L. Immunologic checkpoint blockade in lung cancer. Semin Oncol. 2015 Jun;42(3):402-17. doi: 10.1053/j.seminoncol.2015.02.013. Epub 2015 Feb 19.

  PMID: 25965358 BACKGROUND

• Tecentriq Package Insert, 06May 2016 http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761034s000lbl.pdf

  BACKGROUND

• Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA Jr, Anders RA, Sosman JA, Moslehi JJ. Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med. 2016 Nov 3;375(18):1749-1755. doi: 10.1056/NEJMoa1609214.

  PMID: 27806233 BACKGROUND

• Nishino M, Giobbie-Hurder A, Gargano M, Suda M, Ramaiya NH, Hodi FS. Developing a common language for tumor response to immunotherapy: immune-related response criteria using unidimensional measurements. Clin Cancer Res. 2013 Jul 15;19(14):3936-43. doi: 10.1158/1078-0432.CCR-13-0895. Epub 2013 Jun 6.

  PMID: 23743568 BACKGROUND

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Ross HJ, Kozono D, Wang XF, Urbanic JJ, Williams TM, Nelson GD, Carbone DP, Chung D, Robb R, Byun WY, Talabere T, DuFrane C, Bara I, Schulze K, Brockman M, Gao J, Vokes EE, Stinchcombe TE. Atezolizumab Before and After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: A Phase II Nonrandomized Controlled Trial. JAMA Oncol. 2024 Sep 1;10(9):1212-1219. doi: 10.1001/jamaoncol.2024.1897.

  PMID: 39052256 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Helen J. Ross, MD
• Organization: Mayo Clinic

Ross.Helen@mayo.edu

4803018000

Study Officials

• Helen Ross, MD

  Mayo Clinic

  STUDY CHAIR

• Monica Bertagnolli, MD

  Alliance Foundation Trials

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2017
• First Posted: April 5, 2017
• Study Start: November 1, 2017
• Primary Completion: June 1, 2020
• Study Completion: October 1, 2022
• Last Updated: May 24, 2023
• Results First Posted: May 24, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)