Clinical Trial 20530

• Overview

  Study Title:

  Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Alectinib, Entrectinib, or Vemurafenib Plus Cobimetinib in Patients with Stages I-III Non-Small Cell Lung Cancer with ALK, ROS1, NTRK, or BRAF V600E Molecular Alterations

  Summary:

  This trial will evaluate the efficacy and safety of targeted therapies in participants with resectable Stage IIA, IIB, IIIA, and select IIIB (T3N2) resectable and untreated non-small cell lung cancer (NSCLC) tumors with selected molecular alterations.

  Objective:

  The primary efficacy objective for this study is to evaluate the efficacy of each study treatment on the basis of the following endpoint: Determination of major pathologic response (MPR), (defined as less than or equal to 10% residual viable tumor cells) scored by a local pathologist, based on surgical resection as defined by Hellmann et al. 2014 and further outlines in the pathology standard operating procedure (SOP) Secondary Objectives: Pathological regression based on % viable tumor cell assessment (see pathology SOP) Investigator-assessed response ORR per RECIST v1.1 Pathological complete response (pCR), defined as the absence of residual invasive in situ cancer and all sampled regional lymph nodes (i.e., ypT0 ypN0 in the current AJCC staging system), as assessed by the investigator site pathology laboratory Disease-free survival (DFS), defined as the time from the first date of no disease (e.g., date of surgery or date of CR prior surgery) to local or distant recurrence or death due to any cause, whichever occurs first, as determined by the investigator during the adjuvant treatment and observation follow-up Event-free Survival (EFS), defined as the time from first dose to the first documented disease progression, per RECIST v1.1, or local or distant disease recurrence, as determined by the investigator, or death from any cause, whichever occurs first Overall survival (OS), defined as the time from first dose to death from any cause Exploratory Objectives: Evaluate the change in blood ctDNA from baseline to pre-surgery and the correlation with clinical outcome measures Evaluate the blood ctDNA status post-surgery and the correlation with clinical outcome measures Monitoring of ctDNA status and profiles in blood post-surgery over time and correlation with clinical outcome measures Safety Objectives: Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

• Treatments

  Therapies:

  Chemotherapy (NOS); Radiotherapy; Surgery; Therapy (NOS)

• Inclusion Criteria

  Inclusion Criteria for Neoadjuvant Therapy:
  • Pathologically documented NSCLC: Stage IB, IIA, IIB, IIIA, or selected IIIB, (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the American Joint Committee on Cancer (AJCC) Union Internationale Contre le Cancer (UICC) NSCLC staging system.
  • Biomarker testing results from CLIA-certified laboratories and showing at least one of the following abnormalities: ALK fusion, ROS1 fusion, NTRK1/2/3 fusion; BRAF V600 mutation; RET fusion, PD-L-1 expression in >/- 1% tumor cells as determined by FDA approved test.
  • Biomarker testing results used for patient eligibility should be obtained from the most recent tumor biopsy. Alternatively, and for patients with ALK, ROS1, NTRK1/2/3, and RET molecular alterations, molecular testing results used to determine patient eligibility could have been obtained from a recent blood sample (up to 2 months prior to enrollment) described in the study design.
  • Measurable disease, as defined by RECIST v1.1
  • Evaluated by the attending surgeon prior to study enrollment to verify that the primary tumor and any involved lymph nodes are technically completely resectable and verify that the participant is medically operable
  • Adequate pulmonary function to be eligible for surgical resection with curative intent
  • Adequate cardiac function to be eligible for surgical resection with curative intent
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Male participants must be willing to use acceptable methods of contraception
  • Female participants of childbearing potential must agree to use acceptable methods of contraception
  • Participants whose tumors lack radiographic progression
  • ECOG Performance Status of 0 or 1
  • Adequate hematologic and end-organ function
  • Other criteria may apply

• Exclusion Criteria

  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, including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, within 2 years
  • Participants with prior lung cancer that have been in remission for > Major surgical procedure within 28 days prior to Cycle 1, Day 1
  • Participants known to be positive for HIV are excluded if they meet any of the following criteria: CD4+ T-cell count of > Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact participant safety
  • Pregnant or lactating, or intending to become pregnant during the study
  • Other criteria may apply

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