E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced or Metastatic Non-Small Cell Lung Cancer |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 determine the tumor response to MGCD265 in the selected patient population. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of MGCD265 in the selected population.
To evaluate secondary efficacy endpoints with MGCD265 treatment in the selected population.
To assess correlation between selected tumor gene alterations using different analytical techniques in tumor tissue and circulating tumor deoxyribonucleic acid (ctDNA).
To assess change in genetic alteration status in ctDNA with MGCD265 treatment over time in the selected population.
To assess the population pharmacokinetics/pharmacodynamics (PK/PD) of MGCD265 in the selected population. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed NSCLC with metastatic or unresectable, locally advanced disease.
2. Receipt of at least one prior platinum-containing chemotherapy regimen in the advanced disease setting.
3. Molecular analysis of patient-derived samples using a Sponsor approved method and laboratory that demonstrates a genetic alteration activating MET in tumor tissue and/or ctDNA. If eligibility is established using a Sponsor-approved local laboratory, a tumor tissue specimen and/or blood sample is expected to be available for retrospective sequencing in the central laboratory selected by the Sponsor.
4. Measurable disease, as per RECIST version 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
6. Adequate bone marrow and organ function demonstrated by:
-Absolute neutrophil count ≥ 1,000/mm3 (≥ 1.0 × 109/L)
-Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × Upper Limit of Normal (ULN), or ≤ 5.0 x ULN for patients with documented liver metastases. Alkaline phosphatase levels ≤ 2.5 × ULN. In the presence of extensive bone metastases, there is no upper limit for alkaline phosphatase.
-Total bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN for patients with Gilbert Syndrome or documented liver metastases.
7. ≥ 18 years of age.
8. Women of child-bearing potential (WOCBP) or men whose partner is a WOCBP agrees to use contraception while participating in this study, and for a period of 6 months following termination of study treatment.
9. Completed informed consent process, including signing IRB/EC-approved informed consent form.
10. Willing to comply with clinical trial instructions and requirements. |
|
E.4 | Principal exclusion criteria |
1. Prior treatment with a small molecule or antibody inhibitor of MET or HGF.
2. Prior positive test for EGFR mutation or ALK gene rearrangement:
-Testing and documentation is required for patients with adenocarcinoma histology
Testing is not required for patients with non-adenocarcinoma histology; however if documentation of a positive test is available, the patient will not be eligible
3. Most recent prior chemotherapy or investigational agent discontinued ≤2 weeks before first dose date.
4. Absence of recovery from the adverse effects of prior therapy at the time of enrollment to ≤ Grade 2 (excluding alopecia).
5. History of stroke or transient ischemic attack within the previous 6 months.
6. Any of the following cardiac abnormalities:
-Unstable angina pectoris,
-Congestive heart failure ≥ NYHA Class 3, or
-QTc > 480 msec.
7. Known or suspected presence of another malignancy that could be mistaken for metastatic NSCLC during disease assessments.
8. Symptomatic or uncontrolled brain metastases requiring current treatment (less than 4 weeks from last cranial radiation or 2 weeks from last steroids). Known conditions associated with significant risk of intracranial bleeding including but not limited to vascular malformations and pituitary adenoma.
9. Inability to swallow oral medications or pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs.
10. Known hypersensitivity to any of the components of the MGCD265 Drug Product.
11. Pregnancy. WOCBP must have a negative serum or urine pregnancy test documented within the screening period prior start of study drug.
12. Breast-feeding or planning to breast feed during the study or within 6 months after study treatment.
13. Any serious illness, uncontrolled inter-current illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the Investigator’s opinion, would be likely to interfere with the patient’s participation in the study, or with the interpretation of the results. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis will be conducted approximately 12 weeks after the last patient is enrolled, allowing for observation of an early disease response and confirmation of PR or CR. |
|
E.5.2 | Secondary end point(s) |
- Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.
- Secondary efficacy endpoints:
o Duration of Response (DR);
o Progression-Free Survival (PFS);
o 1-Year Survival Rate; and
o Overall Survival (OS).
- Gene alterations in tumor tissue and ctDNA at prescreening/baseline.
- Change in ctDNA through time.
- Blood plasma MGCD265 concentration.
- Blood plasma concentration of selected soluble biomarkers. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Signs and symptoms of the patient’s cancer diagnosis and/or comorbidities present at baseline will be recorded in the CRF as adverse events. |
|
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 | Yes |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Australia |
Canada |
France |
Germany |
Hungary |
Italy |
Korea, Republic of |
Poland |
Spain |
Taiwan |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
Last visit of the last patient undergoing the study. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |