Patients with EGFR mutant Non-Small Cell Lung Cancer who have failed at least 1 previous EGFR-directed TKI and 1 line of platinum-containing doublet chemotherapy MedDRA version: 19.0 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Product Name: Rociletinib
Product Code: CO-1686
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: NA
CAS Number: 1446700-26-0
Sponsors
Clovis Oncology, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with radiological progression on the most recent therapy received 2. Documented evidence of a tumor with 1 or more EGFR activating mutations excluding exon 20 insertion 3. Disease progression confirmed by radiological assessment while receiving treatment with single-agent EGFR-TKI 4. Multiple lines of prior treatment are permitted but patients must have received at least 1 line of treatment with an EGFR TKI and a platinum-containing doublet chemotherapy 5. Have undergone a biopsy of either primary or metastatic tumor tissue within 60 days prior to start of treatment and have tissue available to send to sponsor laboratory or are able to undergo a biopsy during Screening and provide tissue to sponsor laboratory 6. Measureable disease according to RECIST Version 1.1 7. Life expectancy of at least 3 months 8. ECOG performance status of 0 to 1 9. Age = 18 years (in certain territories, the minimum age requirement may be higher e.g., age = 20 years in Japan and Taiwan; age = 21 years in Singapore) 10. Patients should have recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade = 1 from any significant chemotherapy-related toxicities 11. Adequate hematological and biological function, confirmed by local laboratory value se.g. Bone Marrow Function, Hepatic Function, Renal function and Electrolyte within normal range, and Fasting serum glucose within normal ranges. 12. Written consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Any other malignancy associated with a high mortality risk within the next 5 years and for which the patients may be (but not necessarily) currently receiving treatment 2. Known pre-existing interstitial lung disease 3. Tumor small cell transformation by local assessment, irrespective of presence of T790M+ component 4. Patients with leptomeningeal carcinomatosis are excluded. 5. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and that treatment cannot be either discontinued or switched to a different medication (known to have no effect on QT) before starting protocol-specified treatment 6. Prior treatment with rociletinib, or other drugs that target T790M+ mutant EGFR with sparing of WT-EGFR including but not limited to AZD9291, HM61713, and TAS-121 7. Any contraindications for therapy with pemetrexed, paclitaxel, gemcitabine or docetaxel unless a contraindication with respect to one of these drugs will not affect the use of any of the others as a comparator to rociletinib 8. Cardiac abnormalities or history 9. Non-study related surgical procedures = 7 days prior to randomization. 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 6 months after the last dose of study treatment (rociletinib and chemotherapy irrespective of single cytotoxic agent used) 12. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including uncontrolled diabetes, active infection, arterial thrombosis, and symptomatic pulmonary embolism) 13. Any other reason the investigator considers the patient should not participate in the study 14. Treatment with live vaccines initiated less than 4 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Progression-free survival (PFS) according to RECIST Version 1.1 as determined by investigator assessment (invPFS);Timepoint(s) of evaluation of this end point: From start of treatment until it is clear that no further clinical benefit can be achieved.;Main Objective: To compare the anti-tumor efficacy of oral single-agent rociletinib, as measured by investigator assessment of the PFS, with that of single-agent cytotoxic chemotherapy in patients with EGFR-mutated, advanced/metastatic NSCLC after failure of at least 1 previous EGFR-directed TKI and at least 1 line of platinum-containing doublet chemotherapy; Secondary Objective: • To compare secondary measures of clinical efficacy (ORR, DR and OS) between patients randomized to rociletinib or single-agent cytotoxic chemotherapy • To compare the safety and tolerability of rociletinib with that of single-agent cytotoxic chemotherapy • To determine PK of rociletinib using population PK (POPPK) methods and explore correlations between PK, exposure, response, and/or safety findings in patients randomized to rociletinib | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ORR and DR according to RECIST Version 1.1 as determined by investigator assessment • OS • Treatment-emergent AEs, laboratory abnormalities, and ECG abnormalities • Plasma PK parameters for rociletinib based on sparse sampling ;Timepoint(s) of evaluation of this end point: From start of treatment until it is clear that no further clinical benefit can be achieved. | — |
Countries
Australia, France, Germany, Italy, Korea, Republic of, Netherlands, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactDr Lindsey Rolfe
Clovis Oncology UK Ltd
Outcome results
None listed