Lung-MAP: Master Protocol for Treatment of Non-Small Cell Lung Cancer

Accelerating development of cancer therapies by improving clinical trial design

The Problem
Researchers conducting clinical trials of potential cancer treatments often cannot identify effective therapies, in part because the patients enrolled have heterogeneous forms of cancer that respond differently to a given treatment.
The Solution
Lung-MAP is improving clinical trials of potential cancer treatments by characterizing patients’ tumors and then matching patients to sub-studies of treatments relevant to those tumors.

Overview

Lung-MAP, a Master Protocol for Treatment of Non-Small Cell Lung Cancer, is a groundbreaking multi-center clinical trial that uses a multi-sub-study, targeted screening approach to match patients, based on their unique tumor profiles, with sub-studies testing investigational new treatments. Specifically, Lung-MAP uses cutting-edge genomic profiling to determine the genomic alterations, or mutations, which may drive the growth of their cancer. Based on those results, patients are matched to either a bio-marker or a non-matched sub-study. The “non-match” sub-study (currently a randomized study of two cutting-edge immune therapies) includes all screened patients not eligible for any of the biomarker-driven sub-studies. The various sub-studies test therapies suspected to target the genomic alterations or mutations found to be driving the growth of patients’ cancer. Instead of undergoing multiple diagnostic tests to determine eligibility for many different studies, enrollees are tested for genomic alterations just once, according to a master screening protocol, LUNGMAP.

Results & Accomplishments

New LUNGMAP Protocol

  • CTEP (Cancer Therapy Evaluation Program) approved a new LUNGMAP screening protocol that activated on 1/28/19, expanding the trial to all NSCLC histologies and immune oncology combinations for anti-PDL-1 refractory patients, as well as a ctDNA liquid biopsy screening.

Lung-MAP’s Growing Sub-Study Pipeline

  • As of December 13th, 2020, 1,769 patients have been registered to Lung-MAP (under the new LUNGMAP screening protocol); of these, a total of 938 patients have been assigned to sub-studies. Ten sub-studies have been completed and data are now being presented at national and international meetings. The trial has two active sub-studies, with another study expected to launch by early 2021 and the pipeline of new sub-studies continuing to grow. 

Partners

Public-Sector Partners

  • Foundation for the National Institutes of Health
  • Friends of Cancer Research
  • National Cancer Institute – National Clinical Trials Network
  • SWOG Cancer Research Network

Private-Sector Partners

  • Amgen, Inc.*
  • AbbVie, Inc.*
  • AstraZeneca Pharmaceuticals LP*
  • Bristol Myers-Squibb Company*
  • Genentech, a member of the Roche group*
  • Medimmune*
  • Pfizer, Inc.*

*Provides financial or in-kind support for this program.

For a full list, visit: lung-map.org/about/partners

FNIH Contacts

Scientific Publications

CTI

  • Biomarker-driven therapies for previously treated squamous non-small-cell lung cancer (Lung-MAP SWOG S1400): a biomarker-driven master protocol. Redman MW, Papadimitrakopoulou VA, Minichiello K, Hirsch FR, Mack PC, Schwartz LH, Vokes E, Ramalingam S, Leighl N, Bradley J, Miao J, Moon J, Highleyman L, Miwa C, LeBlanc ML, Malik S, Miller VA, Sigal EV, Adam S, Wholley D, Sigman C, Smolich B, Blanke CD, Kelly K, Gandara DR, Herbst RS. Lancet Oncol 2020; 21:1589-601. Read more
  • A Phase II Study of Telisotuzumab Vedotin in Patients With c-MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K, NCT03574753). Waqar SN, Redman MW, Arnold SM, Hirsch FR, Mack PC, Schwartz LH, Gandara DR, Stinchcombe TE, Leighl NB, Ramalingam SS, Tanna SH, Raddin RS, Minichiello K, Bradley JD, Kelly K, Herbst RS, Papadimitrakopoulou VA. Clin Lung Cancer 2020:online ahead of print. Read more
  • SWOG S1400B (NCT02785913), a phase II study of GDC-0032 (taselisib) for previously treated PI3K-positive patients with stage IV squamous cell lung cancer (Lung-MAP sub-study).  Langer CJ, Redman MW, Wade JL, 3rd, Aggarwal C, Bradley JD, Crawford J, Stella PJ, Knapp MH, Miao J, Minichiello K, Herbst RS, Kelly K, Gandara DR, Read more Papadimitrakopoulou VA. J Thorac Oncol 2019;14:1839–46.
  • SWOG S1400D (NCT02965378), a phase II study of the fibroblast growth factor receptor inhibitor AZD4547 in previously treated patients with fibroblast growth factor pathway-activated stage iv squamous cell lung cancer (Lung-MAP sub-study).  Aggarwal C, Redman MW, Lara PN, Jr., Borghaei H, Hoffman P, Bradley JD, Newman AJ, 3rd, Feldman MJ, Minichiello K, Miao J, Mack PC, Papadimitrakopoulou VA, Herbst RS, Kelly K, Gandara DR. J Thorac Oncol 2019;14:1847–52.  Read more
  • Master protocols in lung cancer: experience from Lung Master Protocol.  Lam VK, Papadimitrakopoulou V. Curr Opin Oncol 2018;30:92–97. Read more
  • Overview of thoracic oncology trials in cooperative groups around the globe. Salahudeen A, Patel MI, Baas P, Curran W, Bradley JD, Gandara D, Goss P, Mok T, Ramalingam SS, Vokes EE, Malik S, Wakelee H. Clinical Lung Cancer 2016 Jun 27 [Epub ahead of print], 2016. Read more
  • The Master Protocol Concept. Redman MW, Allegra CJ. 2015 Oct;42(5):724-30. Epub 2015 Jul 10. Read more
  • EGFR tyrosine kinase inhibitors in squamous cell lung cancer. Hirsch F, Herbst R, Gandara D. Aug;16(8):872-873, 2015. Read more
  • Lung-MAP--framework, overview, and design principles. Ferrarotto R, Redman MW, Gandara DR, Herbst RS, Papadimitrakopoulou VA. Chin Clin Oncol. 2015 Sep;4(3):36. Read more
  • The promise of lung master protocol for squamous cell carcinoma: one trial to rule them all, one trial to find them…? Wright GM, Russell PA. Ann Transl Med. 2015 Sep;3(15):219. Read more
  • Squamous cell lung cancer: from tumor genomics to cancer therapeutics. Gandara DR, Hammerman PS, Sos ML, Lara PN Jr, Hirsch FR. Clin Cancer Res. 2015 May 15;21(10):2236-43. Read more
  • Innovative Clinical Trials: The LUNG-MAP Study. Steuer CE, Papadimitrakopoulou V, Herbst RS, Redman MW, Hirsch FR, Mack PC, Ramalingam SS, Gandara DR. 2015 May;97(5):488-91. Read more
  • Lung Master Protocol (Lung-MAP)-A Biomarker-Driven Protocol for Accelerating Development of Therapies for Squamous Cell Lung Cancer: SWOG S1400. Herbst RS, Gandara DR, Hirsch FR, Redman MW, LeBlanc M, Mack PC, Schwartz LH, Vokes E, Ramalingam SS, Bradley JD, Sparks D, Zhou Y, Miwa C, Miller VA, Yelensky R, Li Y, Allen JD, Sigal EV, Wholley D, Sigman CC, Blumenthal GM, Malik S, Kelloff GJ, Abrams JS, Blanke CD, Papadimitrakopoulou VA. Clin Cancer Res. 2015 Apr 1;21(7):1514-24. Epub 2015 Feb 13. Read more
  • Consensus report of a joint NCI thoracic malignancies steering committee: FDA workshop on strategies for integrating biomarkers into clinical development of new therapies for lung cancer leading to the inception of "master protocols" in lung cancer. Malik S, Pazdur R, Abrams J, Socinski M, Sause WT, Harpole D, Welch J, Korn E, Ullmann C, Hirsch F. Journal of Thoracic Oncology 9(10):1443-1448, 2014. Read more

Selected Abstracts

  • Lung-MAP (SWOG S1400): Design, implementation, and lessons learned from a biomarker-driven master protocol (BDMP) for previously-treated squamous lung cancer (sqNSCLC). Redman MW, Papadimitrakopoulou V, Minichiello K, Gandara DR, Hirsch FR, Mack PC, Schwartz LH, Vokes EE, Ramalingam SS, Leighl NB, Bradley J, LeBlanc ML, Malik S, Miller VA, Sigal EV, Adam S, Blanke CD, Kelly K, Herbst RS. Journal of Clinical Oncology 2020;38:15_suppl, abstr 9576.
  • A phase II study of durvalumab plus tremelimumab for previously treated patients with acquired resistance to PD-1 checkpoint inhibitor therapy and stage IV squamous cell lung cancer (Lung-MAP Sub-study). Leighl NB, Redman MW, Rizvi NA, Hirsch FR, Mack PC, Schwartz LH, Wade JL, Irvin WJ, Reddy S, Crawford J, Bradley JD, Stinchcombe T, Ramalingam SS, Miao J, Minichiello K, Gandara DR, Herbst RS, Papadimitrakopoulou V, Kelly K. SWOG S1400F (NCT03373760): J Clin Oncol 2020;38:15_suppl, abstr 9623.
  • A phase III randomized study of nivolumab plus ipilimumab versus nivolumab for previously treated patients with stage IV squamous cell lung cancer and no matching biomarker (Lung-MAP Sub-Study S1400I, NCT02785952).  Bazhenova L, Redman MW, Gettinger SN, Hirsch FR, Mack PC, Schwartz LH, Gandara DR, Bradley JD, Stinchcombe T, Leighl NB, Ramalingam SS, Tavernier SS, Minichiello K, Kelly K, Papadimitrakopoulou V, Herbst RS. J Clin Oncol 2019;37 (suppl):abstr 9014
  • A phase II study of talazoparib (BMN 673) in patients with homologous recombination repair deficiency (HRRD) positive stage IV squamous cell lung cancer (Lung-MAP Sub-Study, S1400G).  Owonikoko TK, Redman MW, Byers LA, Hirsch FR, Mack PC, Schwartz LH, Bradley JD, Stinchcombe T, Leighl NB, Al Baghdadi T, Lara P, Miao J, Kelly K, Ramalingam SS, Herbst RS, Papadimitrakopoulou V, Gandara DR. A phase II study of talazoparib (BMN 673) in patients with homologous recombination repair deficiency (HRRD) positive stage IV squamous cell lung cancer (Lung-MAP Sub-Study, S1400G). J Clin Oncol 2019;37 (suppl):abstr 9022.
  • Phase II study of ABBV-399 (Process II) in patients with C-MET positive stage IV/recurrent lung squamous cell cancer (SCC): LUNG-MAP sub-study S1400K (NCT03574753).  Waqar SN, Redman MW, Arnold SM, Hirsch FR, Mack PC, Schwartz LH, Gandara DR, Stinchcombe T, Leighl NB, Ramalingam SS, Tanna SH, Raddin RS, Minichiello K, Kelly K, Bradley JD, Herbst RS, Papadimitrakopoulou V. J Clin Oncol 2019;37 (suppl):abstr 9075.
  • Future of Novel Agents for Squamous Cell Carcinoma: Lung-MAP Trial [presentation]. Papadimitrakopoulou V. ASCO Annual Meeting 2019 Jun 03.
  • Patient knowledge and expectations related to return of genomic results in the Lung-MAP (SWOG 1400) biomarker-driven clinical trial IASLC 2019.  Roth JA, Trivedi MS, Gray S, Patrick D, Burke W, Delaney D, Watabayashi K, Litwin P, Shah P, Crew KD, Yee M, Redman M, Papadimitrakopoulou VA, Karen Kelly, Gandara DR, Hershman DL, Ramsey SD. World Conference on Lung Cancer 2019:abstr OA07.06.
  • First comprehensive report of impact of genomic alterations, chemotherapy, targeted therapy and immunotherapy on outcomes in the genomics driven squamous master protocol LungMAP.  Papadimitrakopoulou V, Redman MW, Gandara DR, Hirsch FR, Mack PC, Langer CJ, Edelman MJ, Aggarwal C, Socinski MA, Gettinger SN, Waqar SN, Griffin K, Leighl NB, Owonikoko TK, Bradley JD, Ramalingam SS, Stinchcombe T, Blanke CD, Kelly K, Roy S. Herbst RS. J Clin Oncol 2018;36 (suppl):abstr 9019.
  • A phase II study of Durvalumab (MEDI4736) for previously treated patients with stage IV squamous NSCLC (SqNSCLC): Lung-MAP Sub-study SWOG S1400A. Papadimitrakopoulou V, Redman M, Borghaei H, Wagar SN, Robert F, Kiefer GJ, McDonough S, Herbst R, Kelly K, Gandara D. European Lung Cancer Conference, 2017.
  • A phase II study of gdc-0032 (taselisib) for previously treated PI3K positive patients with stage IV squamous cell lung cancer (sqNSCLC): lung-map sub-study SWOG S1400B. Wade JL, Redman M, Langer C, Aggarwal C, Bradley JD, Crawford J, Miao J, Griffin K, Herbst R, Kelly K, Gandara D. American Society of Clinical Oncology Annual Meeting, poster session, 2017.Read more
  • A phase II study of palbociclib (p) for previously treated cell cycle gene alteration positive patients (pts) with stage IV squamous cell lung cancer (scc): lung-map sub-study SWOG S1400C. Edelman M, Redman M, Albain KS, McGary E, Rafique N, Petro D, Wagar S, Griffin K, Miao J, Papadimitrakopoulou V, Kelly K, Gandara D, Herbst R. American Society of Clinical Oncology Annual Meeting, poster session, 2017. Read more
  • Phase II study of the FGFR inhibitor AZD4547 in previously treated patients with FGFR pathway-activated stage IV squamous cell lung cancer (sqNSCLC): lung-map sub-study SWOG S1400D. Aggarwal C, Redman M, Lara P, Borghaei H, Hoffman P, Bradley JD, Griffin K, Miao J, Mack PC, Papadimitrakopoulou V, Herbst R, Kelly K, Gandara D. American Society of Clinical Oncology Annual Meeting, poster session, 2017. Read more
  • Integrating traditional Electronic Data Capture (EDC) with new systems. Cook C, Phillips T, Leblanc M. Society for Clinical Trials (abstract not available), 2016.
  • Lung-MAP (S1400) Lung Master Protocol: Accrual and Genomic screening updates. Papadimitrakopoulou V, Redman M, Gandara D, Hirsch F, Mack P, Borghaei H, Langer C, Wade J, Edelman M, Albain K, Lara P, Aggarwal C, Socinski M, Gettinger S, Bazhenova L, Malik S, Miller V, McDonough S, Sigal E, Kelly K, Herbst R. World Conference on Lung Cancer, 2016. Read more

Media

  • The Cancer Letter (February 21, 2020): Lung-MAP: A fiver-year recap on the first master protocol trial in cancer research Read more
  • Targeted Oncology (August 21, 2019): Precision Medicine Trials and Molecular Testing Guidelines Expand to Reach More Patients Read more
  • FNIH Press Release (January 29, 2019): Lung-MAP Precision Medicine Trial Expands to Include More Patients Read more
  • Refer to the Lung-MAP website: lung-map.org/news-media/archive/press