E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030155 |
E.1.2 | Term | Oesophageal carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 evaluate the Objective Response Rate (ORR) per RECIST 1.1 assessed by central imaging vendor in all subjects and in subjects whose tumors are classified as GEP intermediate or high and in subjects whose tumors are classified as GEP high. |
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E.2.2 | Secondary objectives of the trial |
(1) To evaluate safety and tolerability of pembrolizumab. (2) To evaluate Duration of Response (DOR), and Progression-free Survival (PFS) per RECIST 1.1 assessed by central imaging vendor and Overall Survival (OS). (3) To evaluate PD-L1 IHC in esophageal cancer for its utility to predict pembrolizumab efficacy. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (blood and tissue) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time |
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E.3 | Principal inclusion criteria |
Subjects must: - Be ≥ 18 years of age on the day of signing the informed consent. - Have an ECOG performance status of 0 or 1. - Have a life expectancy greater than 3 months. - Have histologically proven advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ. - Have experienced documented objective radiographic or clinical disease progression on two previous lines of standard therapy. This study will only include third-line subjects. Third line subjects are defined as those who have progressed during or after receiving at least one dose of standard therapy given in a second line setting. - Have measurable disease based on RECIST 1.1 as determined by central imaging vendor assessment. - Provide either a newly obtained or archival tissue sample for intratumoral immunerelated GEP and for PD-L1 by immunohistochemistry analysis. Newly-obtained tissue is preferred. - Have demonstrated adequate organ function. - Negative pregnancy test for females of child bearing potential prior to starting study and male and female subjects of childbearing potential must be willing to use an adequate method of contraception. |
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E.4 | Principal exclusion criteria |
The subject will be excluded from participating in the trial if the subject: - Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. - Has an active autoimmune disease that has required systemic treatment in past 2 years. - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Has received prior anti-cancer mAb, chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to first dose of trial treatment or who has not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to a previously administered agent. - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or has previously participated in Merck pembrolizumab (MK-3475) clinical trials. - Has a known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer, and in situ or intramucosal pharyngeal cancer. - Has received a live vaccine within 30 days of planned start of study therapy. - Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. - Has a known history of Human Immunodeficiency Virus (HIV) infection. - Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). - Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. - Has an active infection requiring systemic therapy. - Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. - Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) - RECIST 1.1 assessed by central imaging vendor |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
No interim analysis is currently planned. This end point will be evaluated at end of study. |
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E.5.2 | Secondary end point(s) |
1. Duration of Response (DOR) - RECIST 1.1 assessed by central imaging vendor 2. Progression-free Survival (PFS) - RECIST 1.1 assessed by central imaging vendor 3. Overall survival (OS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
No interim analysis is currently planned. These end points will be evaluated at end of study. |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
Denmark |
France |
Germany |
Israel |
Japan |
Korea, Republic of |
Norway |
United Kingdom |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |