None listed
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive nam
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be willing and able to provide documented 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. 2.Be =18 years of age on the day of signing informed consent. 3. Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) solid tumor that is incurable and for which prior standard first-line treatment has failed. Patients must have progressed on or be intolerant to therapies that are known to provide clinical benefit. There is no limit to the number of prior treatment regimens. 4. Have one of the following advanced (unresectable and/or metastatic) tumor types: (A) Anal Squamous Cell Carcinoma, (B) Biliary Adenocarcinoma (gallbladder or biliary tree (intrahepatic or extrahepatic cholangiocarcinoma) except Ampulla of Vater Cancers, (C) Neuroendocrine Tumors (well- and moderately-differentiated), of the lung, appendix, small intestine, colon, rectum, or pancreas, (D) Endometrial Carcinoma (sarcomas and mesenchymal tumors are excluded), (E) Cervical Squamous Cell Carcinoma, (F) Vulvar Squamous Cell Carcinoma, (G) Small Cell Lung Carcinoma, (H) Mesothelioma (Malignant Pleural Mesothelioma), (I) Thyroid Carcinoma (Papillary or Follicular Subtypes), (J) Salivary Gland Carcinoma (sarcomas and mesenchymal tumors are excluded) OR (K) Any advanced solid tumor (except CRC), which is MSI-H. (L) Any advanced solid tumor (including CRC*) which is dMMR/MSI-H in patients from mainland China who are of Chinese descent. (M) Any advanced solid tumor that has failed at least one line of therapy and is TMB-H (=10 mut/Mb, F1CDx assay), excluding dMMR/MSI-H tumors. 5. Have submitted an evaluable tissue sample for biomarker analysis from a tumor lesion not previously irradiated (exceptions may be considered after consultation with and approval by the Sponsor) (See Laboratory Manual for detailed instructions). The tumor tissue submitted for analysis must be from a single tumor tissue specimen and of sufficient quantity and quality to allow assessment of ALL required primary biomarkers. 6. If enrollment in Groups A-J has moved to biomarker enrichment, have a tumor that is positive for one or more of the pre-specified primary biomarker(s), as assessed by the central laboratory. These enrichment biomarkers may be PD-L1 expression by IHC (at a percentage to be prespecified), a positive tumor RNA GEP score (at a prespecified cut-off), and/or tumor MSI-H. 7. Have radiologically measurable disease based on RECIST 1.1. Independent central radiologic review must confirm the presence of radiologically measureable disease based on RECIST 1.1 for the subject to be eligible to participate in the trial (see Site Imaging Manual for detailed instructions). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 8. Have a performance status of 0 or 1 on the ECOG Performance Scale. This performance status must be confirmed within 3 days prior to the first dose of pembrolizumab or the subject must be excluded. 9. Life expectancy of at least 3 months. 10. Demonstrate adequate organ function as described in the protocol 11. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a WOCBP OR • Is a WOCBP and usi
Exclusion criteria
Exclusion criteria: 1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment. 2. 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. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor. 3. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) or treatment with drugs (e.g. neomercazol, carbamazole, etc.) that function to decrease the generation of thyroid hormone by a hyperfunctioning thyroid gland (e.g. in Graves' disease) is not considered a form of systemic treatment of an autoimmune disease. 4. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from an AE due to mAbs administered more than 4 weeks earlier. 5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from an AE due to a previously administered agent. 6. Has a known additional malignancy within 2 years prior to enrollment with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively resected in situ cancers. 7. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided these brain metastases are stable (without evidence of progression by imaging over a period of at least 4 weeks and any neurologic symptoms have returned to baseline), they have no evidence of new or enlarging brain metastases (confirmed by imaging within 28 days of the first dose of trial treatment), and they are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 8. Has known glioblastoma multiforme of the brainstem. 9. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease. 10. Has an active infection requiring systemic therapy. 11. 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. 12. Has known psychiatric or substance abuse disorders that would interfere with he participant's/subject's ability to cooperate with the requirements of the trial. 13. 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. 14. Has previously participated in any other pembrolizumab (MK-3475) trial, or received prior therapy with an anti-PD-1, an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1: To evaluate the ORR to pembrolizumab, based on RECIST 1.1 as assessed by independent central radiologic review, in biomarkerunselected subjects with any one of multiple types of advanced (metastatic and/or unresectable) solid tumors (Groups A-J) 2: To evaluate the ORR to pembrolizumab, based on RECIST 1.1 as assessed by independent central radiologic review, in biomarkerselected subjects with any one of multiple types of advanced solid tumors (Groups A-K) .The primary biomarkers to be evaluated are (1) tumor expression of PD-L1 by IHC (Groups A-J), (2) tumor GEP by RNA analysis (Groups A-J), and (3) tumor MSI by DNA analysis (Groups A-J) or routine local testing (Group K). 4: (Group M only): To evaluate the ORR to pembrolizumab, based on RECIST 1.1 as assessed by independent central radiologic review, in subjects who have advanced solid tumors that have failed at least one systemic line of therapy and which are TMB-H (=10 mut/Mb, F1CDx assay), excluding dMMR/MSI-H tumors. ;Secondary Objective: The following secondary objectives will be evaluated across the ten specified tumor types (Groups A-J): -To evaluate DOR (based on RECIST 1.1 as assessed by independent central radiologic review) in subjects receiving pembrolizumab and the relationship between DOR and tumor PD-L1 expression and GEP score -To evaluate PFS (based on RECIST 1.1 as assessed by independent central radiologic review ) in subjects receiving pembrolizumab and the relationship between PFS and tumor PD-L1 expression and GEP score - To evaluate OS in subjects receiving pembrolizumab and the relationship between OS and tumor PD-L1 expression and GEP score The following secondary objectives will be evaluated across all tumor types (Groups A-K): -To determine the safety and tolerability of pembrolizumab Refer to protocol for complete list;Primary end point(s): ORR based on RECIST 1.1 as assessed by independent central radiologic review;Timepoint(s) of evaluation of this end point: The tr | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and Tolerability Duration of response (DOR) Progression-free survival (PFS) Overall survival (OS) (PK) for the 200 mg iv Q3W fixed dosing regimen;Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints will be summarized at the time that the primary analysis is conducted; however, these secondary endpoints are not likely to be mature at that time. | — |
Countries
Denmark, France, Germany, Italy, Netherlands, Norway, Spain, United Kingdom
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme LLC
Outcome results
None listed