A Phase 2/3 clinical study to evaluate the safety and efficacy of the study medication CO-1686 compared to erlotinib in subjects with Non-Small Cell Lung Cancer

• Register: EUCTR
• Last refreshed on: 23 July 2018
• Main ID: EUCTR2014-000370-19-DE
• Date of registration: 24/10/2014
• Prospective Registration: Yes
• Primary sponsor: Clovis Oncology, Inc.
• Public title: A Phase 2/3 clinical study to evaluate the safety and efficacy of the study medication CO-1686 compared to erlotinib in subjects with Non-Small Cell Lung Cancer
• Scientific title: TIGER-1: A Randomized, Open-Label, Phase 2/3 Study of CO-1686 or Erlotinib as First-Line Treatment of Patients with EGFR-Mutant Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC) - TIGER-1
• Date of first enrolment: 14/01/2015
• Target sample size: 1200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000370-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: yes; Other specify the comparator: Erlotinib; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Hong Kong, Israel, Italy, Korea, Republic of, Spain, Taiwan, United States

Contacts

• Name: Dr Lindsey Rolfe
• Affiliation: Clovis Oncology UK Ltd

• Name: Dr Lindsey Rolfe
• Affiliation: Clovis Oncology UK Ltd

Key inclusion & exclusion 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. Measureable disease according to RECIST Version 1.1
5. Life expectancy of at least 3 months
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
7. Age = 18 years (in certain territories, the minimum age requirement may be higher; e.g., age = 20 years in Japan and Taiwan)
8. Adequate hematological and biological function, confirmed by the following laboratory values e.g. Bone Marrow Function, Hepatic Function, Renal function and Electrolyte within normal range

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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 900

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
8.Prior treatment with EGFR TKIs, CO-1686 or other drugs that target mutant EGFR
9. Cardiac abnormalities or history
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC)
MedDRA version: 18.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864

Intervention(s)

Product Name: Rociletinib
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: CO-1686
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-

Product Name: Rociletinib
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: CO-1686
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: Tarceva
Product Name: Erlotinib
Product Code: Erlotinib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ERLOTINIB
CAS Number: 183321-74-6
Other descriptive name: ERLOTINIB HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Tarceva
Product Name: Erlotinib
Product Code: Erlotinib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ERLOTINIB
CAS Number: 183321-74-6
Other descriptive name: ERLOTINIB HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Tarceva
Product Name: Erlotinib
Product Code: Erlotinib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ERLOTINIB
CAS Number: 183321-74-6
Other descriptive name: ERLOTINIB HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Main 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/metastatic NSCLC

Secondary Objective: • To compare secondary measures of clinical efficacy ORR, DR,and OS following treatment of CO-1686 with that of erlotinib
• To assess PFS, ORR, DR, and OS in patients with baseline T790M
mutations based on central allele-specific polymerase chain reaction
(PCR) EGFR mutation assay
• To assess quality of life (QOL) using the patient-reported outcomes
(PRO) of 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), the Dermatology Life Quality Index (DLQI), and the EQ-5D instrument in patients receiving CO-1686 versus erlotinib
• To evaluate safety and tolerability of CO-1686 versus erlotinib in
patients with advanced/metastatic NSCLC whose tumors have EGFRactivating mutations
• 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

Primary end point(s): PFS according to RECIST Version 1.1 as determined by investigator review (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.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From start of treatment until it is clear that no further clinical benefit can be achieved.

Secondary end point(s): • ORR and DR according to RECIST 1.1 as determined by investigator
review, and OS
• invPFS, ORR, DR, and OS in patients with baseline T790M mutations
confirmed by central EGFR mutation assay
•Change from baseline in QOL as measured using the PRO of EORTC
QLQ-C30, EORTC QLQ-LC13, the DLQI, and the EQ-5D following
treatment with CO-1686 versus erlotinib
• Treatment-emergent AEs, laboratory abnormalities and ECG
abnormalities
• Plasma PK parameters for CO-1686 based on sparse sampling

Secondary ID(s)

CO-1686-022

Source(s) of Monetary Support

Clovis Oncology, Inc.