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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02628067




Registration number
NCT02628067
Ethics application status
Date submitted
9/12/2015
Date registered
11/12/2015
Date last updated
21/10/2024

Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)
Scientific title
A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors (KEYNOTE 158)
Secondary ID [1] 0 0
163196
Secondary ID [2] 0 0
3475-158
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Anal Carcinoma 0 0
Anal Cancer 0 0
Biliary Cancer 0 0
Cholangiocarcinoma 0 0
Bile Duct Cancer 0 0
Neuroendocrine Tumor 0 0
Carcinoid Tumor 0 0
Endometrial Carcinoma 0 0
Endometrial Cancer 0 0
Cervical Carcinoma 0 0
Cervical Cancer 0 0
Vulvar Carcinoma 0 0
Vulvar Cancer 0 0
Small Cell Lung Carcinoma 0 0
Small Cell Lung Cancer (SCLC) 0 0
Mesothelioma 0 0
Thyroid Carcinoma 0 0
Thyroid Cancer 0 0
Salivary Gland Carcinoma 0 0
Salivary Gland Cancer 0 0
Salivary Cancer 0 0
Parotid Gland Cancer 0 0
Advanced Solid Tumors 0 0
Colorectal Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Thyroid
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Bowel - Anal
Cancer 0 0 0 0
Other cancer types
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - pembrolizumab
Treatment: Other - pembrolizumab

Experimental: Pembrolizumab 200 mg - Participants will receive pembrolizumab 200 mg intravenously on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years of treatment).

Experimental: Pembrolizumab 400 mg - Participants with any advanced solid tumor that has failed at least one line of therapy and is Tumor- Mutational Burden-High (TMB-H), excluding participants with mismatch repair deficient (dMMR/MSI-H) tumors. The dosing regimen for this cohort will be 400 mg every 6 weeks (Q6W) for up to 18 administrations (up to approximately 2 years of treatment).


Treatment: Other: pembrolizumab
intravenous infusion

Treatment: Other: pembrolizumab
intravenous infusion
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 10.5 years
Secondary outcome [1] 0 0
Duration of Response (DOR)
Timepoint [1] 0 0
Up to approximately 10.5 years
Secondary outcome [2] 0 0
Progression Free Survival (PFS)
Timepoint [2] 0 0
Up to approximately 10.5 years
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Up to approximately 10.5 years
Secondary outcome [4] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [4] 0 0
Up to approximately 27 months
Secondary outcome [5] 0 0
Percentage of Participants who Discontinue Study Intervention due to AEs
Timepoint [5] 0 0
Up to approximately 2 years

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/12/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/05/2027
Actual
Sample size
Target
1609
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
MSD Australia - North Ryde
Recruitment postcode(s) [1] 0 0
- North Ryde
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Brazil
State/province [2] 0 0
Sao Paulo
Country [3] 0 0
Chile
State/province [3] 0 0
Santiago
Country [4] 0 0
Colombia
State/province [4] 0 0
Bogota
Country [5] 0 0
Denmark
State/province [5] 0 0
Glostrup
Country [6] 0 0
France
State/province [6] 0 0
Paris
Country [7] 0 0
Germany
State/province [7] 0 0
Haar
Country [8] 0 0
Israel
State/province [8] 0 0
Hod Hasharon
Country [9] 0 0
Italy
State/province [9] 0 0
Rome
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul
Country [11] 0 0
Mexico
State/province [11] 0 0
Mexico City
Country [12] 0 0
Netherlands
State/province [12] 0 0
Haarlem
Country [13] 0 0
Norway
State/province [13] 0 0
Drammen
Country [14] 0 0
Peru
State/province [14] 0 0
Lima
Country [15] 0 0
Poland
State/province [15] 0 0
Warsaw
Country [16] 0 0
Portugal
State/province [16] 0 0
Paco D'arcos
Country [17] 0 0
Russian Federation
State/province [17] 0 0
Moscow
Country [18] 0 0
South Africa
State/province [18] 0 0
Midrand
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/study/NCT02628067
Trial related presentations / publications
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 Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020 Jan 1;38(1):1-10. doi: 10.1200/JCO.19.02105. Epub 2019 Nov 4.
O'Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus Acosta A, Miller WH Jr, Safra T, Italiano A, Mileshkin L, Amonkar M, Yao L, Jin F, Norwood K, Maio M. Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. Gynecol Oncol. 2022 Aug;166(2):245-253. doi: 10.1016/j.ygyno.2022.06.005. Epub 2022 Jul 11.
Even C, Delord JP, Price KA, Nakagawa K, Oh DY, Burge M, Chung HC, Doi T, Fakih M, Takahashi S, Yao L, Jin F, Norwood K, Hansen AR. Evaluation of pembrolizumab monotherapy in patients with previously treated advanced salivary gland carcinoma in the phase 2 KEYNOTE-158 study. Eur J Cancer. 2022 Aug;171:259-268. doi: 10.1016/j.ejca.2022.05.007. Epub 2022 Jun 28.
Maio M, Ascierto PA, Manzyuk L, Motola-Kuba D, Penel N, Cassier PA, Bariani GM, De Jesus Acosta A, Doi T, Longo F, Miller WH, Oh DY, Gottfried M, Xu L, Jin F, Norwood K, Marabelle A. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Ann Oncol. 2022 Sep;33(9):929-938. doi: 10.1016/j.annonc.2022.05.519. Epub 2022 Jun 6.
Maio M, Amonkar MM, Norquist JM, Ascierto PA, Manzyuk L, Motola-Kuba D, Penel N, Cassier PA, Bariani GM, De Jesus Acosta A, Doi T, Longo F, Miller WH Jr, Oh DY, Gottfried M, Wang R, Norwood K, Marabelle A. Health-related quality of life in patients treated with pembrolizumab for microsatellite instability-high/mismatch repair-deficient advanced solid tumours: Results from the KEYNOTE-158 study. Eur J Cancer. 2022 Jul;169:188-197. doi: 10.1016/j.ejca.2022.03.040. Epub 2022 May 16.
Shapira-Frommer R, Mileshkin L, Manzyuk L, Penel N, Burge M, Piha-Paul SA, Girda E, Lopez Martin JA, van Dongen MGJ, Italiano A, Xu L, Jin F, Norwood K, Ott PA. Efficacy and safety of pembrolizumab for patients with previously treated advanced vulvar squamous cell carcinoma: Results from the phase 2 KEYNOTE-158 study. Gynecol Oncol. 2022 Aug;166(2):211-218. doi: 10.1016/j.ygyno.2022.01.029. Epub 2022 Mar 28.
Marabelle A, Cassier PA, Fakih M, Kao S, Nielsen D, Italiano A, Guren TK, van Dongen MGJ, Spencer K, Bariani GM, Ascierto PA, Santoro A, Shah M, Asselah J, Iqbal S, Takahashi S, Piha-Paul SA, Ott PA, Chatterjee A, Jin F, Norwood K, Delord JP. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. Lancet Gastroenterol Hepatol. 2022 May;7(5):446-454. doi: 10.1016/S2468-1253(21)00382-4. Epub 2022 Feb 1.
O'Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus Acosta A, Miller WH Jr, Safra T, Italiano A, Mileshkin L, Xu L, Jin F, Norwood K, Maio M. Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study. J Clin Oncol. 2022 Mar 1;40(7):752-761. doi: 10.1200/JCO.21.01874. Epub 2022 Jan 6.
Yap TA, Nakagawa K, Fujimoto N, Kuribayashi K, Guren TK, Calabro L, Shapira-Frommer R, Gao B, Kao S, Matos I, Planchard D, Chatterjee A, Jin F, Norwood K, Kindler HL. Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study. Lancet Respir Med. 2021 Jun;9(6):613-621. doi: 10.1016/S2213-2600(20)30515-4. Epub 2021 Apr 6.
Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, Chung HC, Kindler HL, Lopez-Martin JA, Miller WH Jr, Italiano A, Kao S, Piha-Paul SA, Delord JP, McWilliams RR, Fabrizio DA, Aurora-Garg D, Xu L, Jin F, Norwood K, Bang YJ. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020 Oct;21(10):1353-1365. doi: 10.1016/S1470-2045(20)30445-9. Epub 2020 Sep 10.
Piha-Paul SA, Oh DY, Ueno M, Malka D, Chung HC, Nagrial A, Kelley RK, Ros W, Italiano A, Nakagawa K, Rugo HS, de Braud F, Varga AI, Hansen A, Wang H, Krishnan S, Norwood KG, Doi T. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies. Int J Cancer. 2020 Oct 15;147(8):2190-2198. doi: 10.1002/ijc.33013. Epub 2020 May 2.
Strosberg J, Mizuno N, Doi T, Grande E, Delord JP, Shapira-Frommer R, Bergsland E, Shah M, Fakih M, Takahashi S, Piha-Paul SA, O'Neil B, Thomas S, Lolkema MP, Chen M, Ibrahim N, Norwood K, Hadoux J. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Neuroendocrine Tumors: Results From the Phase II KEYNOTE-158 Study. Clin Cancer Res. 2020 May 1;26(9):2124-2130. doi: 10.1158/1078-0432.CCR-19-3014. Epub 2020 Jan 24.
Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. doi: 10.1200/JCO.18.01265. Epub 2019 Apr 3.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02628067