Previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as erlotinib or gefitinib MedDRA version: 19.0 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864 MedDRA version: 19.0 Level: LLT Classification code
Conditions
Interventions
Product Code: CO-1686
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: To be determined
CAS Number: 1374640-70-6
Current Sponsor
Sponsors
Clovis Oncology, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For Phase 1 and Phase 2: •Histologically or cytologically confirmed metastatic or unresectable locally advanced, recurrent NSCLC •Documented evidence of any activating mutation in the EGFR determined by either deoxyribonucleic acid (DNA) sequencing or polymerase chain reaction (PCR)-based testing of the NSCLC tumor using central laboratory assessment as documented evidence. •Have undergone a biopsy of either primary or metastatic tumor tissue within 60 days of dosing study drug and have tissue available to send to sponsor lab or are able to undergo a biopsy during screening. No change (except for washout or dose adjustment if required to manage adverse effects) in antitumor therapy regimen is allowed between the biopsy and CO-1686 initiation. •Life expectancy of at least 3 months •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 •Age =18 years •Adequate hematological and biological function, confirmed by the following laboratory values: Bone Marrow Function -Absolute neutrophil count (ANC) = 1.5 x 10e9/L -Platelets >100.0 × 10e9/L -Hemoglobin =9 g/dL (or 5.6 mmol/L) Electrolytes -Potassium and magnesium within normal range. Patients may receive supplements to meet this requirement Hepatic Function -Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 × upper limit of normal (ULN); if liver metastases, =5 × ULN -Bilirubin =2 × ULN Renal Function -Serum creatinine =1.5 × ULN •Written consent on an Institutional Review Board/Independent Ethics Committee-approved Informed Consent Form (ICF) prior to any study-specific evaluation Patients enrolling into Phase 1 must also meet the following inclusion criteria: •Prior treatment with EGFR-directed therapy (e.g. erlotinib, gefitinib, neratinib, afatinib, or dacomitinib [PF299804]). Prior chemotherapy, including intervening chemotherapy, is allowed. -The washout period for an EGFR TKI is a minimum of 3 days. -The washout period for chemotherapy is a minimum of 14 days. -Any toxicity related to prior treatment must have resolved to Grade 1 or less. •Be willing and able to eat a high-fat breakfast on Day 1 of the study (only applicable to food-effect cohort) Patients enrolling into Phase 2 (Cohort A) must also meet the following inclusion criteria: •Disease progression while on treatment with EGFR-directed therapy (e.g. erlotinib, gefitinib, neratinib, afatinib, or dacomitinib [PF299804]). Prior chemotherapy, including intervening chemotherapy before planned inititation of CO-1686, is allowed. a) The washout period an EGFR TKI is a minimum of 3 days b) The washout period for chemotherapy is a minimum of 14 days - Any toxicity related to prior treatment must have resolved to Grade 1 or less •Documented evidence of T790M mutation in EGFR determined by PCR-based testing of the tumor tissue using sponsor central lab following dis
Exclusion criteria
Exclusion criteria: Any of the following criteria will exclude patients from study participation: •Documented evidence of an Exon 20 insertion activating mutation in the EGFR •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 •History of interstitial lung disease related to prior EGFR inhibitor therapy •Patients with Leptomeningeal carcinomatosis are excluded. Other CNS metastases are only permitted if treated, asymptomatic, and stable (not requiring steroids for at least 4 weeks prior to start of study treatment). •Treatment with prohibited medications (e.g., concurrent anticancer therapy including other chemotherapy, radiation therapy, or hormonal treatment [except corticosteroids and megesterol acetate], or immunotherapy) =14 days prior to treatment with CO-1686 •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 •Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia’s method (QTcF) >450 msec (males) or >470 msec (females), •Family history of long QT syndrome b. Inability to measure QT interval on ECG c. Resting bradycardia < 55 beats/min •Implantable pacemaker or implantable cardioverter defibrillator •Treatment with any medication known to produce QT prolongation (see Appendix C for a partial list of prohibited medicines) •Non-study 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. •Females who are pregnant or breastfeeding •Refusal to use adequate contraception for fertile patients (females and males) for 6 months after the last dose of CO-1686 •Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled psychiatric condition, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism) •Any other reason the investigator considers the patient should not participate in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: To evaluate the toxicity profile of escalating doses of CO-1686 and to determine the MTD and RP2D To characterize the PK profile of CO-1686 Phase 2: To evaluate tumor response (ORR + duration of response) to CO-1686 in patients with T790M ; Secondary Objective: Phase 1: To characterize the PK profile of CO-1686 after a high-fat breakfast vs in the fasted state To evaluate the effects of CO-1686 on the QT/QTc interval To evaluate tumor response (overall response rate [ORR]+duration of response) of CO1686 Phase 2: To evaluate object response rate (ORR), duration of response, and progression-free survival [PFS] in patients treated with CO-1686. To evaluate the toxicity and tolerability of CO-1686 To evaluate overall survival (OS) disease control rate (DCR) and progression-free survival [PFS] in patients treated with CO-1686 To characterize the pharmacokinetics (PK) of CO-1686 using population PK (POPPK) methods and explore correlations between PK, exposure, response, and/or safety findings For a full list of secondary and exploratory objectives please see Protocol 7.1 Section . ; Primary end point(s): Phase 1: -The incidence of Grade 3 or 4 adverse events (AEs) and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs) -PK parameters including area under the curve from time zero to time t (AUC0-t), AUC from time zero to infinity (AUC0-8), maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T1/2), elimination rate constant (kel), volume of distribution at steady state after nonintravenous administration (Vss/F), and total plasma clearance (Cl/F) for CO-1686 Phase 2: | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Not applicable; Secondary end point(s): Phase 1: -PK parameters Cmax and AUC for CO-1686 (fasted and fed) -Change from baseline in QT/QTc interval -ORR and duration of response per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Exploratory Endpoints: -Change from baseline in patient-reported outcomes -Concordance of the presence of T790M mutation in blood and tumor tissue samples -Detection of T790M in urine samples Phase 2: -ORR, duration of response and PFS per RECIST Version 1.1 as determined by independent radiology review (IRR) -The incidence of AEs, clinical laboratory abnormalities, and electrocardiogram (ECG) abnormalities -OS, DCR and PFS per RECIST Version 1.1 as determined by investigator assessment -Plasma PK parameters for CO-1686 at Cycle 1 Day 1 and Cycle 1 Day 15 for a subset of patients; CO-1686 metabolite profile in the Day 15 plasma samples for a subset of patients; Plasma PK parameters for CO-1686 based on sparse sampling of all patients -Change from baseline in patient reported outcomes -Change from baseline in QT/QTc interval Exploratory endpoints: -Concordance of the presence of T790M mutation in blood and tumor tissue samples -Detection of T790M in urine samples -Time to treatment failure | — |
Countries
Australia, Poland, United States
Contacts
Public ContactDr Lindsey Rolfe
Clovis Oncology UK Ltd
Outcome results
None listed