Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)

Cervical Cancer Clinical Trial

Official title:

A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors (KEYNOTE 158)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02628067
• Other study ID #: 3475-158
• Secondary ID: 163196MK-3475-15
• Status: Recruiting
• Phase: Phase 2
• Start date: December 18, 2015
• Est. completion date: May 4, 2027

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, participants with multiple types of advanced (unresectable and/or metastatic) solid tumors who have progressed on standard of care therapy will be treated with pembrolizumab (MK-3475).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1609
• Est. completion date: May 4, 2027
• Est. primary completion date: May 4, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically-documented, advanced solid tumor of one of the following types:

• Anal Squamous Cell Carcinoma

• Biliary Adenocarcinoma (gallbladder or biliary tree (intrahepatic or extrahepatic cholangiocarcinoma) except Ampulla of Vater cancers)

• Neuroendocrine Tumors (well- and moderately-differentiated) of the lung, appendix, small intestine, colon, rectum, or pancreas

• Endometrial Carcinoma (sarcomas and mesenchymal tumors are excluded)

• Cervical Squamous Cell Carcinoma

• Vulvar Squamous Cell Carcinoma

• Small Cell Lung Carcinoma

• Mesothelioma

• Thyroid Carcinoma

• Salivary Gland Carcinoma (sarcomas and mesenchymal tumors are excluded)

• Any advanced solid tumor, with the exception of colorectal carcinoma (CRC), which is Microsatellite Instability (MSI)-High (MSI-H) OR

• Any advanced solid tumor (including Colorectal Carcinoma [CRC]) which is Mismatch Repair Deficient (dMMR)/MSI-H in participants from mainland China who are of Chinese descent. (CRC participants will have a histologically proven locally advanced unresectable or metastatic CRC which is dMMR/MSI-H that has received 2 prior lines of therapy) OR

• 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.

Note: For participants to be eligible for enrollment they must have failed at least one line of standard of care systemic therapy (ie, not treatment naïve), with the exception of CRC participants who must have failed at least 2 lines of standard of care systemic therapy, as per CRC specific eligibility criteria. Participants must not have melanoma or NSCLC.

• Progression of tumor or intolerance to therapies known to provide clinical benefit. There is no limit to the number of prior treatment regimens

• Can supply tumor tissue for study analyses (dependent on tumor type)

• Radiologically-measurable disease

• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to first dose of pembrolizumab

• Life expectancy of at least 3 months

• Adequate organ function

• Female participants of childbearing potential must be willing to use adequate contraception during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: MK-3475 (120 days)

Exclusion Criteria:

• 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 study treatment

• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment

• Active autoimmune disease that has required systemic treatment in the past 2 years

• Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from an adverse event caused by mAbs administered more than 4 weeks earlier

• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of study Day 1 or not recovered from adverse events caused by a previously administered agent

• 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

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

• Has known glioblastoma multiforme of the brain stem

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

• Active infection requiring systemic therapy

• Known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study

• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment

• Previously participated in any other pembrolizumab (MK-3475) study, or received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-Ligand 1 (anti-PD-L1), anti-PD-Ligand 2 (anti-PD-L2), or any other immunomodulating mAb or drug specifically targeting T-cell co-stimulation or checkpoint pathways

• Known history of Human Immunodeficiency Virus (HIV)

• Known active Hepatitis B or C

• Received live vaccine within 30 days of planned start of study treatment

• Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients

• Known history of active tuberculosis (TB, Bacillus tuberculosis)

• Has had an allogenic tissue/solid organ transplant.

Related Conditions & MeSH terms

• Advanced Cancer
• Advanced Solid Tumors
• Anal Cancer
• Anal Carcinoma
• Anus Neoplasms
• Bile Duct Cancer
• Bile Duct Neoplasms
• Biliary Cancer
• Carcinoid Tumor
• Carcinoma
• Cervical Cancer
• Cervical Carcinoma
• Cholangiocarcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms
• Endometrial Cancer
• Endometrial Carcinoma
• Endometrial Neoplasms
• Mesothelioma
• Neoplasms
• Neuroendocrine Tumor
• Neuroendocrine Tumors
• Parotid Gland Cancer
• Salivary Cancer
• Salivary Gland Cancer
• Salivary Gland Carcinoma
• Salivary Gland Neoplasms
• Small Cell Lung Cancer (SCLC)
• Small Cell Lung Carcinoma
• Thyroid Cancer
• Thyroid Carcinoma
• Thyroid Diseases
• Thyroid Neoplasms
• Vulvar Cancer
• Vulvar Carcinoma
• Vulvar Neoplasms

Intervention

Biological:
• pembrolizumab
intravenous infusion
• pembrolizumab
intravenous infusion

Locations

Country	Name	City	State
Australia	MSD Australia	North Ryde
Brazil	MSD Brasil	Sao Paulo
Canada	Merck Canada	Kirkland	Quebec
Chile	Merck Sharp & Dohme (I.A.) Corp.	Santiago
Colombia	MDS Colombia SAS	Bogota
Denmark	MSD Denmark	Glostrup
France	MSD France	Paris
Germany	MSD Sharp & Dohme GmbH	Haar
Israel	Merck Sharp & Dohme Co. Ltd.	Hod Hasharon
Italy	MSD Italia S.r.l.	Rome
Korea, Republic of	MSD Korea LTD	Seoul
Mexico	MSD	Mexico City
Netherlands	Merck Sharp & Dohme BV	Haarlem
Norway	MSD Norge A/S	Drammen
Peru	Merck Sharp & Dohme, Peru S.R.L.	Lima
Philippines	Merck Sharp & Dohme (I.A.) Corporation	Makati
Poland	MSD Polska Sp. Z o.o.	Warsaw
Portugal	Merck Sharp & Dohme Lda.	Paco D'arcos
Russian Federation	Merck Sharp & Dohme IDEA, Inc.	Moscow
South Africa	MSD (Pty) LTD South Africa	Midrand
Spain	Merck Sharp and Dohme de Espana S.A.	Madrid
Taiwan	Merck Sharp & Dohme (I.A.) Corp.	Taipei
United States	Call for Information (Investigational Site 0008)	New Brunswick	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Chile,  Colombia,  Denmark,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Peru,  Philippines,  Poland,  Portugal,  Russian Federation,  South Africa,  Spain,  Taiwan, 

References & Publications (1)

Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of P — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ at any time during the trial. Responses will be determined by independent central radiologic review, with confirmatory assessment as required per RECIST 1.1. Participants with unknown or missing response information will be treated as non-responders. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.	Up to approximately 10.5 years
Secondary	Duration of Response (DOR)	DOR, defined in the subset of participants with a CR or PR, based on RECIST 1.1 as assessed by independent central radiologic review, as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death due to any cause, whichever occurs first. A Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Participants who are alive, have not progressed, have not initiated new anti-cancer treatment, and have not been determined to be lost to follow-up are considered ongoing responders at the time of analysis.	Up to approximately 10.5 years
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from allocation to the first documented disease progression according to RECIST 1.1 as assessed by independent central radiologic review, or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease (PD) is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. Note: The appearance of one or more new lesions is also considered PD. If a participant does not have a documented date of progression or death, PFS will be censored at the date of the last adequate assessment.	Up to approximately 10.5 years
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause. OS will be presented. Censoring will be performed using the date of last known contact for those who are alive at the time of analysis.	Up to approximately 10.5 years
Secondary	Percentage of Participants with Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this intervention. The percentage of participants with AEs will be reported.	Up to approximately 27 months
Secondary	Percentage of Participants who Discontinue Study Intervention due to AEs	An AE is defined as any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The percentage of participants who discontinue study intervention due to AEs will be reported.	Up to approximately 2 years

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary