Details

Details

Title CLVS 2514 (Tiger 1) Protocol entitled: A Randomized, Open-Label, Phase II Study of CO-1686 or Erlotinib First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)

IRB CLVS2514

CC 15-019

Hospital Florida Weston, Main Campus

Phase Phase 2

Disease Lung, Lung - NSCLC (Non-small cell lung cancer)

Drug CO-1686, Erlotinib

Description

Description

Primary Objective
  • To compare the antitumor efficacy of oral single-agent CO-1686 with that of erlotinib as measured by progression free survival (PFS), when administered as a first line targeted treatment to patients with EGFR-mutated, advanced NSCLC
Secondary Objectives
  • To compare secondary measures of clinical efficacy [objective response rate (ORR), duration of response (DR), disease control rate (DCR), and overall survival (OS)] following treatment with CO-1686 versus erlotinib
  • To assess PFS in patients with baseline T790M mutations detected using the standard screening clinical assay (allele-specific PCR)
  • To assess patient-reported outcomes (PRO) using the Dermatology Life Quality Index (DLQI)12 following treatment with CO-1686 versus erlotinib
  • To evaluate safety and tolerability of CO-1686 versus erlotinib
  • To determine PK of CO-1686 in this patient population using population PK (POPPK) methods and explore correlations between PK, exposure, response, and/or safety findings
Exploratory Objectives
  • To compare kinetics of tumor growth between treatment arms measured by rate of change in sum of the longest diameters of target lesions (SLD) or rate of change of estimated or measured assessments of tumor volume
  • To assess patient-reported outcomes (PRO) using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Quality of Life Questionnaire Lung Cancer module (EORTC QLQ-LC13)13 following treatment with CO-1686 versus erlotinib
  • To compare PFS and response rate/duration between treatment arms in patients with baseline T790M+ disease, detected using high-sensitivity research assay
  • To evaluate the safety and efficacy of CO-1686 in patients after radiographic progression on erlotinib and who are T790M+ at progression and crossover to receive CO-1686
  • To evaluate concordance of mutant EGFR detection between tissue and plasma and to assess CO-1686 or erlotinib mediated alterations in mutant EGFR levels over time using circulating tumor DNA (ctDNA) obtained from plasma
  • To explore tissue and blood-based biomarkers that may be predictive of response or primary resistance to CO-1686 or erlotinib and investigate mechanisms of acquired resistance in the tissue and blood of patients who experience clinical progression during treatment with CO-1686 or erlotinib
Inclusion Criteria

Inclusion Criteria

  1. Histologically or cytologically confirmed metastatic or unresectable locally advanced, recurrent NSCLC
  2. Documented evidence of a tumor with one or more activating EGFR mutations excluding exon 20 insertion
  3. Have undergone a biopsy or surgical resection of either primary or metastatic tumor tissue within 60 days of planned randomization and have tissue available to send to sponsor lab or are able to undergo a biopsy during Screening and provide tissue to sponsor lab
  4. No prior EGFR-directed therapy (e.g., erlotinib, gefitinib, neratinib, afatinib, AZD9291 or dacomitinib)
  5. Measureable disease according to RECIST Version 1.1
  6. Life expectancy of at least 3 months
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  8. Age ≥ 18 years (in certain territories, the minimum age requirement may be higher; e.g., age ≥ 20 years in Japan and Taiwan)
  9. Adequate hematological and biological function, confirmed by the following laboratory values:
    • Bone Marrow Function
      • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
      • Platelets >100.0 x 109/L
      • Hemoglobin ≥ 9 g/dL (or 5.6 mmol/L)
    • Hepatic Function
      • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN); if liver metastases, ≤ 5 x ULN
      • Bilirubin ≤ 2 x ULN
    • Renal Function
      • Serum creatinine ≤ 1.5 x ULN
    • Electrolytes
      • Potassium and magnesium within normal range, patients may receive supplements to meet this requirement
Exclusion Criteria

Exclusion Criteria

  1. Documented evidence of an exon 20 insertion activating mutation in the EGFR gene
  2. Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant chemotherapy is permitted if at least 6 months has elapsed between the end of chemotherapy and randomization
  3. Active second malignancy; i.e., patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment
    • Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years prior to first day of study treatment, Cycle 1 Day 1 (C1D1)
  4. Known pre-existing interstitial lung disease (ILD)
  5. Brain metastases
  6. Treatment with prohibited medications [e.g., concurrent anticancer therapy including other chemotherapy, radiation, hormonal treatment (except corticosteroids and megesterol acetate), or immunotherapy] ≤ 14 days prior to first day of study treatment, Cycle 1 Day 1 (C1D1)
  7. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval if that treatment cannot be either discontinued or switched to a different medication (not known to affect QT interval) prior to C1D1
    • See http://crediblemeds.org/ for a list of QT-prolonging medications
  8. Prior treatment with EGFR TKIs, CO-1686 or other drugs that target mutant EGFR
  9. Any of the following cardiac abnormalities or history
    • Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) > 450 ms
    • Inability to measure QT interval on ECG
    • Personal or family history of long QT syndrome
    • Implantable pacemaker or implantable cardioverter defibrillator
    • Resting bradycardia < 55 beats/min
  10. Non-study related surgical procedures ≤ 7 days prior to C1D1. In all cases, the patient must be sufficiently recovered and stable before treatment administration.
  11. Females who are pregnant or breastfeeding
  12. Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of CO-1686 and 2 weeks after the last dose of erlotinib
  13. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism)
  14. Any other reason the investigator considers the patient should not participate in the study