E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020328 |
E.1.2 | Term | Hodgkin's lymphoma |
E.1.2 | System Organ Class | 100000004864 |
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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 determine the safety, tolerability and Overall Response Rate (ORR) of pembrolizumab in each of the three cohorts listed below.
Cohort 1: Subjects with relapsed/refractory classical Hodgkin Lymphoma who have failed to achieve a response, or progressed after auto stem cell transplant (auto-SCT) and have relapsed after treatment with or failed to respond to brentuximab vedotin.
Cohort 2: Subjects with relapsed/refractory classical Hodgkin Lymphoma who were unable to achieve a complete or partial response to salvage chemotherapy and did not receive auto-SCT but have relapsed after treatment with or failed to respond to brentuximab vedotin.
Cohort 3: Subjects with relapsed/refractory classical Hodgkin Lymphoma who have failed to achieve a response to or progressed after auto-SCT and have not received brentuximab vedotin.
These subjects may or may not have received brentuximab vedotin as part of primary treatment or salvage therapy. |
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E.2.2 | Secondary objectives of the trial |
Within each of the 3 cohorts of subjects with R/R cHL:
(1) Objective: Evaluate ORR of pembrolizumab by investigator assessment according to the IWG response criteria; and additionally by independent central review using the 5-point scale according to the Lugano Classification.
(2) Objective: Evaluate Complete Remission Rate (CRR) of pembrolizumab by independent central review and by investigator assessment according to the IWG response criteria; and additionally by independent central review using the 5-point scale according to the
Lugano Classification.
(3) Objective: Evaluate Progression Free Survival (PFS) and Duration of Response (DOR) of pembrolizumab by independent central review and by investigator assessment according to the IWG response criteria.
(4) Objective: Evaluate the Overall Survival (OS) of pembrolizumab. |
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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) 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 |
-Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
-Be 18 years of age on day of signing informed consent.
-Must have a performance status of 0 or 1 on the ECOG Performance Scale.
-Must demonstrate adequate organ function as defined in the protocol, all screening labs should be performed within 7 days of treatment initiation.
-Have relapsed or refractory de novo classical Hodgkin lymphoma and meet the requirements specified for one of the three cohorts in the protocol.
-Have measurable disease by CT scan, as described in the protocol.
-Be able to provide a core or excisional lymph node biopsy from an archival or newly obtained biopsy.
-Female subjects of childbearing potential must test negative for pregnancy within 72 hours of the first dose.
-Female subjects of childbearing potential must use appropriate contraception as specified in the protocol through 120 days after the last dose of study medication.
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E.4 | Principal exclusion criteria |
-Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
-Has a diagnosis of immunosuppression 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 had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
-Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Subjects who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of GVHD.)
-Additional exclusion criteria specified in the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received
MK-3475, including serious adverse events (SAEs) and events of clinical interest (ECIs).
The primary efficacy endpoint is the Overall Response Rate (ORR), defined as the proportion of subjects in the analysis population who have complete remission (CR) or partial remission (PR) using IWG criteria, Cheson 2007 at any time during the study. Response for the primary analysis will be determined by central review. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At each cycle and as clinically deemed. Note. The primary analysis of ORR will be done when the last treated subject has reached the Wk12 response assessment/discontinued study therapy. At that time point, analyses of other efficacy endpoints (DOR, CRR, PFS,OS) will also be done. An efficacy update for all endpoints will be done when the last treated subject has at least reached the Wk24 response assessment/has discontinued study therapy. An update will be done 1 year after the last subject initiated treatment and then 2 years after the last subject initiated treatment (end of the protocol-specified treatment period). Subsequent yearly analyses will be done until the trial is complete, including follow-up information on subjects who enter the retreatment period. |
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E.5.2 | Secondary end point(s) |
The key secondary endpoints are complete remission rate, duration of response, progression-free survival and overall survival. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At each cycle and as clinically deemed. See also note above. |
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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 | 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 | 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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
Brazil |
Canada |
Israel |
Japan |
Russian Federation |
United States |
Austria |
France |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Netherlands |
Norway |
Spain |
Sweden |
United Kingdom |
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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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The overall trial ends when the last subject completes the last trial visit, discontinues from the trial or is lost to follow-up (i.e. the subject is unable to be contacted by the investigator).
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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 | 42 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 42 |
E.8.9.2 | In all countries concerned by the trial days | 0 |