A Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Resectable Non-Small Cell Lung Cancer (NSCLC) - Lung Cancer Mutation Consortium (LCMC3)

A Phase II, Open-Label, Multicenter, Single-Arm Study to Investigate the Efficacy and Safety of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Patients With Stage IB, II, IIIA, or Selected IIIB Resectable and Untreated Non-Small Cell Lung Cancer

This study was designed to evaluate the safety and efficacy of neoadjuvant and adjuvant atezolizumab in participants with resectable Non-Small Cell Lung Cancer (NSCLC). Neoadjuvant therapy consisted of two 21-day cycles with atezolizumab. Following surgery, adjuvant therapy consisted of up to 12 months of atezolizumab in participants who demonstrate clinical benefit with neoadjuvant therapy. All participants who undergo surgery entered a surveillance period, which consisted of standardized blood sample collection and Chest CT Scans, for up to 2 years. All participants were monitored for disease recurrence and survival for up to 3 years after last dose of study drug.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Santa Monica, California, United States, 90404
      • UCLA Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University Of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University; Winship Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute; Brigham and Womens Hospital
    • Danvers, Massachusetts, United States, 01923
      • Mass General/North Shore Cancer
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Inst; Hematology/Oncology
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University; Wash Uni. Sch. Of Med
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering - Monmouth
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center - Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Cancer Center at Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center - Koch
    • New York, New York, United States, 10036
      • New York University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering - Basking Ridge
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Pathologically documented Stage IB, II, IIIA, or selected IIIB, including T3N2 or T4 (by size criteria, not by mediastinal invasion) NSCLC
• Adequate pulmonary and cardiac function
• Available biopsy of primary tumor with adequate samples
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• NSCLC that is clinically T4 by virtue of mediastinal organ invasion or Stage IIIB by virtue of N3 disease
• Any prior therapy for lung cancer within 3 years.
• Prior treatment with anti-PD-1 or PD-L1 therapies
• History or risk of autoimmune disease

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: Atezolizumab; Participants received two cycles of atezolizumab as neoadjuvant therapy prior to surgery. Participants who demonstrated clinical benefit were eligible to receive up to 12 months of atezolizumab.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Atezolizumab was given as 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of each 21-day cycle.; Other Names: RO5541267, MPDL3280A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Major Pathologic Response (MPR)	Major pathologic response (defined as ≤ 10% of viable tumor cells), scored by a pathologist, based on surgical resection as defined by prior studies.	After surgery (approximately 10 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	Objective response rate is the proportion of participants who are objective responders (Complete Response and Partial Response are considered as responders, Stable Disease, Progressive Disease and Not Evaluable are considered as nonresponders) in the PD-L1 positive (TC123IC123) and negative (TC0IC0) groups.	After surgery (approximately 10 weeks)
Percentage of Participants With Major Pathologic Response Rates For Programmed Death Ligand 1 (PD-L1)-Positive Versus PD-L1-Negative Participants	Major pathologic response (defined as ≤ 10% of viable tumor cells), scored by a pathologist, based on surgical resection as defined by prior studies.	After surgery (approximately 10 weeks)
Percentage of Participants With Adverse Events		From Baseline until 90 days after end of treatment (approximately 16.5 months overall)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Chaft JE, Oezkan F, Kris MG, Bunn PA, Wistuba II, Kwiatkowski DJ, Owen DH, Tang Y, Johnson BE, Lee JM, Lozanski G, Pietrzak M, Seweryn M, Byun WY, Schulze K, Nicholas A, Johnson A, Grindheim J, Hilz S, Shames DS, Rivard C, Toloza E, Haura EB, McNamee CJ, Patterson GA, Waqar SN, Rusch VW, Carbone DP; LCMC study investigators. Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial. Nat Med. 2022 Oct;28(10):2155-2161. doi: 10.1038/s41591-022-01962-5. Epub 2022 Sep 12. Erratum In: Nat Med. 2023 Oct 10;:

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2017
• Primary Completion (Actual): May 7, 2020
• Study Completion (Actual): September 5, 2023

Study Registration Dates

• First Submitted: October 5, 2016
• First Submitted That Met QC Criteria: October 5, 2016
• First Posted (Estimated): October 7, 2016

Study Record Updates

• Last Update Posted (Actual): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antibodies; Antibodies, Monoclonal; Atezolizumab
• Other Study ID Numbers: ML39236

Drug and device information, study documents

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