Details

Details

Title TIGER-2: A Phase 2, Open-Label, Multicenter, Safety and Efficacy Study of Oral CO-1686 as 2nd Line EGFR-Directed TKI in Patients with Mutant EGFR Non-Small Cell Lung Cancer (NSCLC) with the T790M Resistance Mutation

IRB CLVS1514

CC 14-775

Hospital Main Campus

Phase Phase 2

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

Drug Oral CO-1686

Description

Description

Primary Objective
  • To evaluate the antitumor efficacy of PO single-agent CO-1686, as measured by ORR, when administered to patients with EGFR-mutated, centrally confirmed T790M-positive and T790M-negative advanced NSCLC after tumor progression on 1 previous EGFR-directed TKI
Secondary Objectives
  • To assess clinical efficacy in patients with centrally confirmed T790M-positive NSCLC:DCR, DR, PFS, and OS following CO-1686 treatment
  • To assess quality of life (QoL) by patient-reported outcomes (PRO) following CO-1686 treatment
  • To evaluate the safety and tolerability of CO-1686
  • To determine PK of CO-1686 using population PK (POPPK) methods and explore correlations between PK, exposure, response, and/or safety findings
Exploratory Objectives
  • To evaluate clinical benefit of continued CO-1686 treatment following disease progression
  • To evaluate concordance of mutant EGFR detection between tissue and plasma and assess CO-1686 mediated alterations in mutant EGFR levels over time using circulating tumor deoxyribonucleic acid (ctDNA) obtained from plasma
  • To explore tissue and blood-based biomarkers that may be predictive of response or primary resistance to CO-1686 and investigate mechanisms of acquired resistance in the tissue and blood of patients who experience clinical progression during treatment with CO-1686
Inclusion Criteria

Inclusion Criteria

  1. Histologically or cytologically confirmed metastatic or unresectable locally advanced, NSCLC
  2. Documented evidence of a tumor with 1 or more EGFR mutations excluding exon 20 insertion
    • Disease progression confirmed by radiologic assessment while receiving treatment with the first single-agent EGFR-TKI (eg, erlotinib, gefitinib, afatinib, or dacomitinib)
      • EGFR-TKI treatment discontinued ≤ 30 days prior to planned initiation of CO-1686 (the washout period for an EGFR inhibitor is a minimum of 3 days)
      • No intervening treatment between cessation of single-agent EGFR-TKI and planned initiation of CO-1686
      • Previous treatment with ≤ 1 prior chemotherapy (excluding prior neo-adjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent)
      • Any toxicity related to prior EGFR inhibitor treatment must have resolved to Grade 1 or less
    • Central laboratory confirmation of the presence of the T790M mutation in tumor tissue in Cohort A and the presence or absence of the T790M mutation in tumor tissue in Cohort B. Centrally indeterminate, unknown or invalid specimens are not acceptable. Biopsy material obtained from either primary or metastatic tumor tissue must have been obtained (and sent to the central laboratory) within 60 days prior to dosing study drug but following disease progression on the first EGFR-TKI.
  3. Measureable disease according to RECIST Version 1.1
  4. Life expectancy of at least 3 months
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  6. Age ≥ 18 years (in certain territories, the minimum age requirement may be higher eg, age ≥ 20 years in Japan and Taiwan)
  7. 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
  8. Written consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF prior to any study-specific evaluation
Exclusion Criteria

Exclusion Criteria

  1. Documented evidence of an exon 20 insertion activating mutation in the EGFR gene
  2. 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
  3. Known pre-existing interstitial lung disease
  4. Cohort A only: Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroids for at least 4 weeks prior to the start of study treatment). Cohort B only: Patients with CNS metastases or leptomeningeal carcinomatosis are excluded.
  5. 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 treatment with CO-1686
  6. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication before starting CO-1686
    • see http://crediblemeds.org/ for a list of QT-prolonging medications (includes all medication under categories of Known, Possible and Conditional risk of Torsades de Pointes)
  7. Prior treatment with CO-1686, or other drugs that target T790M positive mutant EGFR with sparing of WT-EGFR e.g. AZD9291, HM61713, TAS-121
  8. Any of the following cardiac abnormalities or history :
    • Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) > 450 msec
    • 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
  9. Nonstudy-related surgical procedures ≤ 7 days prior to administration of CO-1686. In all cases, the patient must be sufficiently recovered and stable before treatment administration.
  10. Females who are pregnant or breastfeeding
  11. Refusal to use adequate contraception for fertile patients (females and males) while on treatment and for 12 weeks after the last dose of CO-1686
  12. 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)
  13. Any other reason the investigator considers the patient should not participate in the study