Biomarker-Driven Master Protocol to Test Therapies for Previously Treated Patients With Squamous NSCLC

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In an article published in The Lancet Oncology, Redman et al described the conduct of and findings from the Lung Cancer Master Protocol (Lung-MAP; SWOG S1400), a completed biomarker-driven master protocol designed to address the need for improved therapies for previously treated patients with squamous non­–small cell lung cancer (NSCLC).

As stated by the investigators, “Lung-MAP (S1400) was created to establish an infrastructure for biomarker screening and rapid regulatory intent evaluation of targeted therapies and was the first biomarker-driven master protocol initiated with the U.S. National Cancer Institute (NCI).”

Study Details

Lung-MAP (S1400) was performed within the NCI National Clinical Trials Network in a public-private partnership. Eligible patients were adults with stage IV or recurrent squamous NSCLC who had received prior treatment with platinum-based chemotherapy and had an Eastern Cooperative Oncology Group performance status of 0 to 2.

The study consisted of a next-generation sequencing screening component and a clinical trial component, including biomarker-driven substudies and nonmatch substudies for patients ineligible for biomarker-driven substudies. Patients were either prescreened and received substudy assignment at progression, or were screened at progression and received substudy assignment after testing. Patients experiencing progression in one substudy could be enrolled into other substudies.

All research related to Lung-MAP (S1400) is complete.

Key Findings

Between June 2014 and January 2019, 1,864 patients were enrolled; of these, 1,841 (98.9%) had available tissue for analysis. Among the 1,841, 1,674 (90.9%) had biomarker results; of these, 1,404 (83.9%) received a substudy assignment. Of the 1,404 assigned patients, 655 (46.7%) were registered to a substudy.

The biomarker-driven substudies evaluated:

  • Taselisib (targeting PIK3CA alterations; vs docetaxel)
  • Palbociclib (cell cycle gene alterations; vs docetaxel)
  • AZD4547 (FGFR alterations; vs docetaxel)
  • Rilotumumab plus erlotinib (MET-positive)
  • Talazoparib (homologous recombination repair deficiency)
  • Telisotuzumab vedotin (MET-positive).

The nonmatch substudies evaluated:

  • Durvalumab (vs docetaxel) and nivolumab plus ipilimumab (vs nivolumab) for those patients not treated with prior anti–PD-L1/PD-1 therapy
  • Durvalumab plus tremelimumab for patients whose disease relapsed after anti–PD-L1/PD-1 therapy.

Among the substudies, 143 eligible patients were registered to receive a molecularly targeted treatment as first study treatment; 56 eligible patients were randomly assigned to docetaxel before early closure of docetaxel arms and subsequent closure of docetaxel-containing substudies due to futility or before completion of accrual; and 315 anti-PD-1 or anti-PD-L1–naive eligible patients were registered to receive an anti-PD-1 or anti-PD-L1 therapy (durvalumab, nivolumab, or nivolumab plus ipilimumab) as first study treatment.

The combined data from the substudies showed responses (complete or partial, confirmed or unconfirmed) in 10 (7.0%) of 143 patients receiving targeted therapy, 53 (16.8%) of 315 receiving anti–PD-1 or anti–PD-L1 therapy for immunotherapy-naive disease, and 3 (5.4%) of 56 receiving docetaxel.  

Median overall survival was 5.9 months (95% confidence interval [CI] = 4.8–7.8 months) in the targeted therapy groups, 7.7 months (95% CI = 6.7–9.2 moths) in the docetaxel groups, and 10.8 months (95% CI = 9.4–12.3) in the anti–PD-1 or anti–PD-L1 treatment–containing groups.

Median progression-free survival was 2.5 months (95% CI = 1.7–2.8 months) in the targeted therapy groups, 2.7 months (95% CI = 1.9–2.9 months) in the docetaxel groups, and 3.0 months (95% CI = 2.7–3.9 months) in the anti–PD-1 or anti–PD-L1 treatment–containing groups.

The investigators concluded: “Lung-MAP (S1400) met its goal to quickly address biomarker-driven therapy questions in squamous NSCLC. In early 2019, a new screening protocol was implemented expanding to all histological types of NSCLC and to add focus on immunotherapy combinations for anti–PD-1 and anti–PD-L1 therapy–relapsed disease. With these changes, Lung-MAP continues to meet its goal to focus on unmet needs in the treatment of advanced lung cancers.”

Mary W. Redman, PhD, of the SWOG Statistics and Data Management Center and Clinical Research Division, Fred Hutchinson Cancer Research Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the National Institutes of Health, and AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Genentech, and Pfizer through the Foundation for the National Institutes of Health. For full disclosures of the study authors, visit