KEYMAKER-U01 Substudy 1: Efficacy and Safety Study of Pembrolizumab (MK-3475) Plus Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Advanced Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) PLUS chemotherapy in combination with vibostolimab (MK-7684), MK-5890, or MK-4830 in treatment-naïve participants with advanced squamous or non-squamous NSCLC.
This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pembrolizumab+Vibostolimab+Carboplatin + Paclitaxel On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS vibostolimab IV PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV in Cycles 5-35 (total treatment duration: up to approximately 2 years). |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Carboplatin
IV infusion
Other Names:
Drug: Paclitaxel
IV infusion
Other Names:
Biological: Vibostolimab
IV infusion
Other Names:
|
| Experimental: Pembrolizumab+Vibostolimab+Carboplatin + Pemetrexed On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years). |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Carboplatin
IV infusion
Other Names:
Drug: Pemetrexed
IV infusion
Other Names:
Biological: Vibostolimab
IV infusion
Other Names:
|
| Experimental: Pembrolizumab+MK-5890+Carboplatin+Paclitaxel On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m^2 IV PLUS MK-5890 IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS MK-5890 IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years). |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Carboplatin
IV infusion
Other Names:
Drug: Paclitaxel
IV infusion
Other Names:
Biological: MK-5890
IV infusion
|
| Experimental: Pembrolizumab+MK-5890+Carboplatin+Pemetrexed On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV PLUS MK-5890 IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS pemetrexed 500 mg/m^2 IV Q3W PLUS MK-5890 IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years). |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Carboplatin
IV infusion
Other Names:
Drug: Pemetrexed
IV infusion
Other Names:
Biological: MK-5890
IV infusion
|
| Experimental: Pembrolizumab+MK-4830+Carboplatin+Paclitaxel On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years). |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Carboplatin
IV infusion
Other Names:
Drug: Paclitaxel
IV infusion
Other Names:
Biological: MK-4830
IV infusion
|
| Experimental: Pembrolizumab+MK-4830+Carboplatin+Pemetrexed On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years). |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Carboplatin
IV infusion
Other Names:
Drug: Pemetrexed
IV infusion
Other Names:
Biological: MK-4830
IV infusion
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 24 months]
ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.
Secondary Outcome Measures
- Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 24 months]
PFS is defined as the time from first dose of study treatment until either the earliest date of documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, 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. The appearance of one or more new lesions is also considered PD.
- Number of Participants Who Experience One or More Adverse Events (AEs) [Up to approximately 27 months]
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [Up to approximately 24 months]
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous or nonsquamous NSCLC
-
Participants with nonsquamous NSCLC who are not eligible for an approved targeted therapy
-
Is able to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation
-
Has not received prior systemic treatment for their metastatic NSCLC
-
Is able to complete all screening procedures within the 35-day screening window
-
Has adequate organ function within 10 days of initiation of study treatment
-
Male participants must agree to use contraception and should refrain from donating sperm during the treatment period and for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy
-
Female participants must not be pregnant or breastfeeding, and at least one of the following conditions apply:
-
Not a woman of childbearing potential (WOCBP), OR
-
A WOCBP who agrees to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy
Exclusion Criteria:
-
Has a diagnosis of small cell lung cancer
-
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 before the first dose of study treatment
-
Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
-
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
-
Has an active autoimmune disease that has required systemic treatment in the past 2 years
-
Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
-
Has an active infection requiring systemic therapy
-
Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment administration, or New York Heart Association Class III or IV congestive heart failure
-
Has a known history of HIV infection
-
Has a known history of Hepatitis B or known active Hepatitis C virus infection
-
Has had major surgery <3 weeks before the first dose of study treatment
-
Is expected to require any other form of antineoplastic therapy while on study
-
Has symptomatic ascites or pleural effusion (if receiving pemetrexed; Alimta®, Eli Lilly)
-
Has a history or current evidence of a gastrointestinal (GI) condition (e.g. inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
-
Is getting chemotherapy and has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, or peritoneal carcinomatosis
-
Has preexisting neuropathy that is moderate in intensity
-
Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease
-
Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), or anti-PD-L2 agent or prior therapy targeting other immunoregulatory receptors or mechanisms
-
Is currently receiving either strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C8 (CYP2C8) that cannot be discontinued for the duration of the study
-
Is currently receiving strong or moderate inducers of CYP3A4 or CYP2C8 that cannot be discontinued for the duration of the study
-
Is unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), other than aspirin dose less than or equal to 1.3 gm/day for a 5-day period (8-day period for long acting agents such as peroxicam), for participants who will receive pemetrexed
-
Is unable or unwilling to take folic acid or vitamin B12 supplementation, for participants who will receive pemetrexed
-
Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed or any of their excipients
-
Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment
-
Has received a live vaccine within 30 days before the first dose of study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed
-
Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
-
Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose of study treatment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks before the first dose of study treatment (including participants who had previous immunomodulatory therapy with residual irAEs)
-
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment
-
Previously had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
-
Is pregnant or 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
-
Has had an allogenic tissue/solid organ transplant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Banner MD Anderson Cancer Center ( Site 0001) | Gilbert | Arizona | United States | 85234 |
| 2 | City of Hope ( Site 0014) | Duarte | California | United States | 91010 |
| 3 | UCSF Medical Center at Mission Bay ( Site 0007) | San Francisco | California | United States | 94158 |
| 4 | Georgetown University ( Site 0036) | Washington | District of Columbia | United States | 20007 |
| 5 | University of Kentucky Markey Cancer Center ( Site 0019) | Lexington | Kentucky | United States | 40536-0293 |
| 6 | MedStar Franklin Square Medical Center ( Site 0033) | Baltimore | Maryland | United States | 21237 |
| 7 | Massachusetts General Hospital ( Site 0003) | Boston | Massachusetts | United States | 02114 |
| 8 | Dana Farber Cancer Institute ( Site 0002) | Boston | Massachusetts | United States | 02215 |
| 9 | Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031) | Omaha | Nebraska | United States | 68130 |
| 10 | Dartmouth Hitchcock Medical Center ( Site 0016) | Lebanon | New Hampshire | United States | 03766 |
| 11 | John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037) | Hackensack | New Jersey | United States | 07601 |
| 12 | Laura and Isaac Perlmutter Cancer Center ( Site 0034) | New York | New York | United States | 10016 |
| 13 | Cleveland Clinic ( Site 0006) | Cleveland | Ohio | United States | 44195 |
| 14 | Ohio State University Comprehensive Cancer Center ( Site 0015) | Columbus | Ohio | United States | 43210 |
| 15 | Abramson Cancer Center of the University of Pennsylvania ( Site 0010) | Philadelphia | Pennsylvania | United States | 19104 |
| 16 | The University of Texas MD Anderson Cancer Center ( Site 0009) | Houston | Texas | United States | 77030 |
| 17 | Petz Aladar Megyei Oktato Korhaz ( Site 0062) | Gyor | Gyor-Moson-Sopron | Hungary | 9024 |
| 18 | Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0061) | Szolnok | Jasz-Nagykun-Szolnok | Hungary | 5000 |
| 19 | Orszagos Koranyi Pulmonologiai Intezet ( Site 0060) | Budapest | Hungary | 1121 | |
| 20 | Soroka Medical Center ( Site 0072) | Beer-Sheva | Israel | 8457108 | |
| 21 | Rambam Health Care Campus-Oncology ( Site 0076) | Haifa | Israel | 3109601 | |
| 22 | Shaare Zedek Medical Center ( Site 0075) | Jerusalem | Israel | 9103102 | |
| 23 | Meir Medical Center ( Site 0071) | Kfar-Saba | Israel | 4428164 | |
| 24 | Rabin Medical Center ( Site 0074) | Petah Tikva | Israel | 4941492 | |
| 25 | Chaim Sheba Medical Center ( Site 0070) | Ramat Gan | Israel | 5262000 | |
| 26 | Sourasky Medical Center ( Site 0077) | Tel Aviv | Israel | 6423906 | |
| 27 | Azienda Ospedaliera Universitaria Careggi ( Site 0173) | Florence | Firenze | Italy | 50134 |
| 28 | Policlinico Gemelli di Roma ( Site 0174) | Roma | Lazio | Italy | 00168 |
| 29 | IRCCS Ospedale San Raffaele ( Site 0171) | Milano | Italy | 20132 | |
| 30 | Seoul National University Bundang Hospital ( Site 0081) | Seongnam-si | Kyonggi-do | Korea, Republic of | 13620 |
| 31 | Severance Hospital ( Site 0080) | Seoul | Korea, Republic of | 03722 | |
| 32 | Samsung Medical Center ( Site 0082) | Seoul | Korea, Republic of | 06351 | |
| 33 | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Pluca i Klatki Pier | Warszawa | Mazowieckie | Poland | 02-781 |
| 34 | Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0152) | Koszalin | Zachodniopomorskie | Poland | 75-581 |
| 35 | ICO L Hospitalet ( Site 0090) | Hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 36 | Hospital Universitario Quiron Madrid ( Site 0091) | Pozuelo de Alarcon | Madrid | Spain | 28223 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 3475-01A
- MK-3475-01A
- KEYMAKER-U01A
- 2020-001626-56