Previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor MedDRA version: 20.0 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Product Name: CO-1686
Product Code: CO-1686
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not applicable
CAS Number: 1446700-26-0
Current Sponsor code: CO-1686
Other descriptive name:
Sponsors
Clovis Oncology, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Except where specified, inclusion criteria are applicable to both Cohorts A and B of the study. 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) o 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) o No intervening treatment between cessation of single agent EGFR TKI and planned initiation of CO 1686 o Previous treatment with = 1 prior chemotherapy (excluding prior neo adjuvant or adjuvant chemotherapy or chemoradiotherapy with curative intent) o 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 o Absolute neutrophil count (ANC) = 1.5 x 10^9/L o Platelets > 100.0 × 10^9/L o Hemoglobin = 9 g/dL (or 5.6 mmol/L) • Hepatic Function o Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 × upper limit of normal (ULN); if liver metastases, = 5 × ULN o Bilirubin = 2 × ULN • Renal Function o Serum creatinine = 1.5 × ULN • Electrolytes oPotassium 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 81 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 144
Exclusion criteria
Exclusion criteria: Except where specified, exclusion criteria are applicable to both Cohorts A and B of the study. 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 (eg, 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 wild type EGFR eg, 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 (eg, 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main 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 T790 negative advanced NSCLC after tumor progression on 1 previous EGFR–directed TKI ;Secondary Objective: • To assess clinical efficacy in patients with centrally confirmed T790M positive NSCLC: disease control rate (DCR), duration of response (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 the pharmacokinetics (PK) of CO-1686 using population PK (POPPK) methods and explore correlations between PK, exposure, response, and/or safety findings ;Primary end point(s): ORR according to RECIST Version 1.1. For Cohort A, ORR will undergo independent radiology review (IRR) and in Cohort B, scans will be assessed by IRR if needed as a supporting analysis.;Timepoint(s) of evaluation of this end point: The ORR is the best overall response recorded from the start of the treatment until disease progression or recurrence. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • DR, DCR and PFS according to RECIST Version 1.1 as determined by IRR • ORR, DR, DCR and PFS according to RECIST Version 1.1 as determined by Investigator Assessment • OS • Change from baseline in patient reported outcomes using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ C30), EORTC Quality of Life Questionnaire Lung Cancer module (EORTC QLQ LC13), and the Dermatology Life Quality Index (DLQI) • Treatment emergent adverse events (AEs), laboratory abnormalities and ECG abnormalities • Plasma PK parameters for CO-1686 based on sparse sampling ;Timepoint(s) of evaluation of this end point: From start of treatment until disease progression | — |
Countries
Australia, Canada, France, Germany, Hong Kong, Korea, Republic of, Netherlands, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactDr Lindsey Rolfe
Clovis Oncology UK Ltd
Outcome results
None listed