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A Phase Ib Clinical Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) in Combination with Cisplatin and Pemetrexed in Treatment-naive Participants with Advanced Malignant Pleural Mesothelioma (KEYNOTE-A17).

A Phase Ib Study of Pembrolizumab in Combination with Cisplatin and Pemetrexed in Advanced MPM

19

- Mean Age: 67.8 years - Sex: Male 15 participants (78.9%), Female 4 participants (21.1%) -Race: Japanese (19 participants [100.0%])

Started: 19 participants Completed: 6 participants Discontinued the study: 13 participants

Percentage of all-cause mortality: 68.42% (13/19 participants) Percentage of participants with serious adverse events: 36.84% (7/19 participants) Serious adverse events with an incidence of >= 10%: pneumonia bacterial and pneumonitis (10.53% each) Percentage of participants with non-serious adverse events: 100.0% (all 19 participants) Non-serious adverse events with an incidence of >= 20%: nausea (84.21%), constipation (68.42%), anaemia(57.89%), diarrhoea (52.63%), malaise (47.37%), white blood cell count decreased and dysgeusia (36.84% each), neutropenia and rash (31.58% each), hiccups, decreased appetite and dry skin (26.32% each), neutrophil count decreased, hyponatraemia, pyrexia and insomnia (21.05% each)

Primarily Outcome Safety DLT -Analysis population: DLT analysis population; 18 participants -The number of participants who met the criteria for DLT during Cycle 1: 2 participants (11.1%) Adverse event (AE) -Analysis population: All participants who received at least 1 dose of study intervention (All Participants as Treated [APaT] population); 19 participants -Percentage of participants who experienced one or more AE: 100.0% (all 19 participants) Discontinued study treatment due to AE -Analysis population: APaT population; 19 participants -Percentage of participants who discontinued study treatment due to AE: 31.6% (6/19 participants)

Secondary Outcome Efficacy The objective response rate (ORR) as assessed by investigator -Analysis population: APaT population; 19 participants -ORR as assessed by investigator: 73.7% Disease control rate (DCR) -Analysis population: APaT population; 19 participants -DCR: 94.7% Duration of response (DOR) -Analysis population: APaT population with confirmed objective responses; 14 participants -The median of DOR: 16.8 months

Safety Treatment with pembrolizumab in combination with cisplatin and pemetrexed in participants with advanced/unresectable MPM has a manageable safety profile that is generally consistent with the known safety profiles of pembrolizumab monotherapy and cisplatin plus pemetrexed combination. Efficacy Pembrolizumab in combination with cisplatin and pemetrexed shows promising antitumor activity for treatment-naive participants with advanced/unresectable MPM with high ORR and durable responses.

Yes

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

MSD K.K.

KITANOMARU SQUARE,1-13-12,Kudan-kita,Chiyoda-ku,Tokyo 102-8667,Japan

msdjrct@merck.com

MSDJRCT inquiry mailbox

MSD K.K.

KITANOMARU SQUARE,1-13-12,Kudan-kita,Chiyoda-ku,Tokyo 102-8667,Japan

+81-3-6272-1957

msdjrct@merck.com

completed

Dec. 09, 2019

Interventional

Single arm study, open(masking not used), uncontrolled control, single assignment, treatment purpose

treatment purpose

1

- Has histologically confirmed diagnosis of advanced/unresectable malignant pleural mesothelioma (MPM)
- Have at least one measurable disease, which is systemic therapy naive, radiologically assessed by the local site investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST)
- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days before the first administration
- Has a life expectancy of at least 3 months
- Demonstrate adequate organ function
- Male participants are eligible to participate if they agree to refrain from donating sperm, plus either agree to remain abstinent or agree to use contraception unless confirmed to be azoospermic
- 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 woman of child bearing potential (WOCBP), OR is a WOCBP and using a contraceptive method or be abstinent from heterosexual intercourse

- A WOCBP who has a positive pregnancy test within 72 hours prior to treatment allocation
- Has received prior therapy with an anti-programmed cell-death 1 (anti PD-1), anti programmed cell-death ligand 1 (anti-PD-L1), or anti programmed cell-death ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,CTLA-4, OX-40, CD137)
- Has previously received systemic anti-cancer therapy (including investigational agents) to MPM. Note: Participants who received (neo) adjuvant previously may be eligible, only if the last dose of chemotherapy was completed at least 6 months before registration. Such participants must have recovered from all adverse events (AEs) due to previous (neo) adjuvant therapies to <=Grade 1 or baseline. Participants with <=Grade 2 neuropathy may be eligible.
- Received radiation therapy to the lung that is > 30 gray (Gy) within 6 months of the first dose of trial treatment
- Completed palliative radiotherapy within 7 days of the first dose of trial treatment. Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- Had a major surgery within 3 months prior to the first administration in this study
- Has received a live vaccine within 30 days prior to the first dose of study drug
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has had a severe hypersensitivity reaction (>=Grade 3) to treatment a monoclonal antibody/components of the study intervention
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Is being treated for pericardial effusion, or has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

Both

advanced malignant pleural mesothelioma

investigational material(s)
Generic name etc : MK-3475 + pemetrexed + cisplatin
INN of investigational material : pembrolizumab, pemetrexed, cisplatin Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material :
- MK-3475 (Solution for Infusion), 200 mg, IV Infusion, Q3W, Day 1 in each cycle up to 35 cycles
- Pemetrexed (Solution for Infusion), 500 mg/m2, IV Infusion, Q3W, Day 1 in each cycle up to 4-6 cycles
- Cisplatin(Solution for Infusion), 75 mg/m2, IV Infusion, Q3W, Day 1 in each cycle up to 4-6 cycles

control material(s) Generic name etc :
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

Safety
- Dose limiting toxicities (DLTs) rate
- AEs
- Discontinuing study treatment due to AEs

Efficacy
- Objective response (OR): confirmed complete response (CR) or partial response (PR)
- Disease control (DC): a response of confirmed CR or PR, or stable disease (SD)
- Duration of response (DOR): the time from the first documented evidence of OR (CR or PR) to the earliest date of PD or death due to any cause, whichever comes first, for individuals with a confirmed CR or PR.

+81-45-520-2222

Nov. 20, 2019