| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| First-Line Treatment of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer (NSCLC) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029514 |
| E.1.2 | Term | Non-small cell lung cancer NOS |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
• 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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
|
|
| E.4 | Principal 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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| PFS according to RECIST Version 1.1 as determined by investigator review (invPFS) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| From start of treatment until it is clear that no further clinical benefit can be achieved. |
|
| E.5.2 | 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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| From start of treatment until it is clear that no further clinical benefit can be achieved. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| France |
| Germany |
| Hong Kong |
| Israel |
| Italy |
| Korea, Republic of |
| Spain |
| Taiwan |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Upon discontinuation of original study treatment or crossover phase, all patients will enter the follow-up phase to monitor for survival status and subsequent NSCLC approximately every 3 months (12 ± 1 week) until death or sponsor decision, whichever comes first. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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