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A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03918278
Recruitment Status : Active, not recruiting
First Posted : April 17, 2019
Last Update Posted : May 25, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief Summary:
This is a 2 part study. Part 1 is a dose escalation to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) dose of MK-0482 administered as monotherapy and in combination with pembrolizumab (MK-3475) in participants with advanced solid tumors for which there is no available therapy which may convey clinical benefit. Part 2 is expansion cohort to determine safety and tolerability of MK-0482 in combination with pembrolizumab with and without chemotherapy in participants with advanced tumor specific cohorts.

Condition or disease Intervention/treatment Phase
Neoplasms Biological: MK-0482 Biological: pembrolizumab Drug: Paclitaxel Drug: Nab-paclitaxel Drug: Gemcitabine Drug: Carboplatin Drug: Pemetrexed Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-0482 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors.
Actual Study Start Date : June 19, 2019
Estimated Primary Completion Date : February 19, 2025
Estimated Study Completion Date : February 19, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: MK-0482 Monotherapy
Participants receive escalating doses of MK-0482 via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).
Biological: MK-0482
IV infusion

Experimental: Part 1: MK-0482 + Pembrolizumab Combination Therapy
Participants receive escalating doses of MK-0482 via IV infusion + pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years).
Biological: MK-0482
IV infusion

Biological: pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part 2: Cohort A
Participants with metastatic triple negative breast cancer (TNBC) first line treatment (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) and paclitaxel 90 mg/m^2 via IV infusion until PD or discontinuation.
Biological: MK-0482
IV infusion

Biological: pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Paclitaxel
IV infusion
Other Names:
  • Nov-Onxol
  • Onxol
  • Paclitaxel Novaplus
  • Taxol

Experimental: Part 2: Cohort B
Participants with recurrent non-operable glioblastoma (GBM) current treatment of second line (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years).
Biological: MK-0482
IV infusion

Biological: pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part 2: Cohort C
Participants with metastatic pancreatic ductal adenocarcinoma (PDAC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years), Nab-Paclitaxel 125 mg/m^2 via IV infusion and gemcitabine 1000 mg/m^2 via IV infusion until PD or unacceptable toxicity that requires discontinuation.
Biological: MK-0482
IV infusion

Biological: pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Nab-paclitaxel
IV infusion
Other Name: Abraxane

Drug: Gemcitabine
IV infusion
Other Name: Gemzar

Experimental: Part 2: Cohort D
Participants with metastatic soft tissue sarcoma (STS) (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years).
Biological: MK-0482
IV infusion

Biological: pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Part 2: Cohort E
Participants with metastatic non-squamous non-small cell lung carcinoma (NSCLC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion plus Pemetrexed 500 mg/m^2 via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) plus carboplatin with desired dose of area under the curve (AUC) 5 and pemetrexed 500 mg/m^2, both administered via IV infusion, followed by maintenance therapy with pemetrexed 500 mg/m^2 via IV infusion for up to a total of 35 administrations (up to approximately 2 years).
Biological: MK-0482
IV infusion

Biological: pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Carboplatin
IV infusion
Other Name: Paraplatin ®

Drug: Pemetrexed
IV infusion
Other Name: Alimta




Primary Outcome Measures :
  1. Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 1 only) [ Time Frame: Cycle 1 (Up to 21 days) ]
    DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity (T); Gr4 hematologic T lasting ≥7 days, except thrombocytopenia (TCP); Gr4 TCP of any duration; Gr3 TCP associated with clinically-significant bleeding; nonhematologic adverse event (AE) ≥Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for >1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; >2 week-delay in starting Cycle 2 due to Tx-related T; Tx-related T resulting in Tx discontinuation during DLT evaluation period; missing >25% of the MK-0482 or any combination component during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.

  2. Number of Participants Who Experience at Least One Adverse Event (AE) [ Time Frame: Up to approximately 27 months ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.

  3. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 24 months ]
    The number of participants who discontinue study treatment due to an AE will be presented.

  4. Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 2 only) [ Time Frame: Up to approximately 28 days from the start of study intervention ]
    DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity (T); Gr4 hematologic T lasting ≥7 days, except thrombocytopenia (TCP); Gr4 TCP of any duration; Gr3 TCP associated with clinically-significant bleeding; nonhematologic adverse event (AE) ≥Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for >1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; >2 week-delay in starting Cycle 2 due to Tx-related T; Tx-related T resulting in Tx discontinuation during DLT evaluation period; missing >25% of the MK-0482 or any combination component during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.


Secondary Outcome Measures :
  1. Minimum Serum Concentration (Cmin) of MK-0482 When Administered as Monotherapy (Part 1 only) [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmin (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.

  2. Cmin of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only) [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmin (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.

  3. Maximum Serum Concentration (Cmax) of MK-0482 When Administered as Monotherapy (Part 1 only) [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmax (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.

  4. Cmax of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only) [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmax (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.

  5. Area Under the Concentration-Time Curve (AUC) of MK-0482 When Administered as Monotherapy (Part 1 only) [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-0482 AUC (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.

  6. AUC of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only) [ Time Frame: At designated time points (Up to approximately 25 months) ]
    Blood samples will be obtained at designated time points for the assessment of MK-0482 AUC (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.

  7. Objective Response Rate (ORR) As Assessed by Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Part 2 only) [ Time Frame: Up to approximately 25 months ]
    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. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented.

  8. ORR As Assessed by Investigator per Response Assessment in Neuro-Oncology (RANO) (Part 2 only) [ Time Frame: Up to approximately 25 months ]
    ORR is defined as the percentage of participants who have a complete response (CR: Disappearance of all target lesions) or a partial response (PR: sum of products of diameters decreased by ≥50% from baseline value) per RANO criteria. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RANO will be presented.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Part 1 only: Has histologically-or cytologically-confirmed advanced/metastatic solid tumors and have received, been intolerant to, or been ineligible for, all treatments known to confer clinical benefit
  • Has measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for Cohort B as assessed by the local site investigator/radiology
  • Has provided an evaluable archival or newly obtained tumor tissue sample
  • Part 1, Arm 1 only: Has ≥1 discrete malignant lesions that are amenable to biopsy
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 95 days after the last dose of chemotherapy: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and 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 ≥1 of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 180 days after the last dose of chemotherapy or 120 days after the last dose of MK-0482 or pembrolizumab, whichever occurs last
  • Part 2 Cohort A, C, and E only: WOCBP must also agree not to donate to others or freeze/store for her own use for the purpose of reproduction during and for at least 180 days after the last dose of chemotherapy
  • Has a negative highly sensitive pregnancy test within 72 hours before the first dose of study treatment
  • Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on anti-retroviral therapy (ART)
  • Has adequate organ function
  • Part 2 Cohort A only: 1) Has histologically confirmed locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) 2) Has received no prior systemic therapy for metastatic TNBC 3) Has tumor programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥1
  • Part 2 Cohort B only: 1) Has confirmed diagnosis of GBM (isocitrate dehydrogenase (IDH) wildtype per 2021 World Health Organization (WHO) classification of tumors of central nervous system) 2) Has received a standard first-line treatment for GBM including surgery and radiation therapy with or without chemotherapy and evidence of disease recurrence or pression by magnetic resonance imaging (MRI) 3) Has time elapsed from prior treatment as per protocol 4) Has Karnofsky performance status (KPS) ≥ 80 within 7 days before start of study treatment 5) Is neurologically stable 6) Has known status of O6-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase (IDH)
  • Part 2 Cohort C only: Has histologically confirmed diagnosis of metastatic PDAC and has received no prior systemic therapy for metastatic pancreatic ductal adenocarcinoma (PDAC) including chemotherapy, biological or targeted therapy and has albumin ≥3.0 g/dL
  • Part 2 Cohort D only: Has histologically confirmed diagnosis of locally advanced or metastatic soft tissue sarcoma (STS) and has received and progressed after one prior line of systemic treatment for advanced STS. Prior treatment in the (neo)adjuvant setting is not counted as a line of treatment for advanced disease
  • Part 2 Cohort E only: Has histologically confirmed diagnosis of Stage IV or recurrent non-operable non-squamous non-small cell lung carcinoma (NSCLC) , has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or c-ros oncogene 1 (ROS1) directed therapy is not indicated as primary therapy and has not received prior systemic treatment for metastatic NSCLC

Exclusion Criteria:

  • Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
  • Has a known additional malignancy that is progressing or has required active treatment within the past 2 years; with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
  • Has known active central nervous system metastases and/or carcinomatous meningitis
  • Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb) and/or any component of pembrolizumab (MK-3475) or MK-0482
  • Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
  • Has an active infection requiring systemic therapy
  • Has a history of interstitial lung disease
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
  • Has known Hepatitis B or C infection
  • Has received prior systemic anticancer therapy, definitive radiotherapy, including investigational agents within 4 weeks (2 weeks for palliative radiation) before the first dose of study treatment
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study treatment
  • Has received an investigational agent or has used an investigational device 4 weeks prior to start of study intervention
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
  • Has had an allogeneic tissue/solid organ transplant in the last 5 years or has evidence of graft-versus-host disease
  • Part 2 only: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or prior therapy targeting other immune-regulatory receptors or mechanisms
  • Part 2 Cohort A only: 1) Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of start of study treatment 2) Has a known sensitivity to any component of paclitaxel or any of its excipients and 3) Is receiving any medication prohibited in combination with paclitaxel unless medication was stopped within 7 days before the start of study treatment
  • Part 2 Cohort B only: 1) Has carcinomatous meningitis 2) Has recurrent tumor 3) Has tumor primarily localized to the brainstem or spinal cord 4) Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease 5) Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan except Grade ≤ Grade I and either post-operative OR stable on at least 2 consecutive MRI scans 6) Requires treatment with moderate or high dose systemic corticosteroids as defined in protocol for at least 3 consecutive days within 2 weeks of start of study treatment and 7) Optune® TTFields within 2 weeks of start of study treatment
  • Part 2 Cohort C only: 1) Has a history of class II-IV congestive heart failure, cerebral vascular event, unstable angina, or myocardial infarction within 6 months of the start of study treatment 2) Has symptomatic ascites, and 3) Has a known hypersensitivity to nab-paclitaxel or gemcitabine, or any of their excipients
  • Part 2 Cohort E only: 1) Has a diagnosis of small cell lung cancer 2) Has symptomatic ascites or pleural effusion 3)Is currently receiving either strong or moderate inhibitors and/or inducers of CYP3A4 or CYP2C8 that cannot be discontinued for the duration of the study 4) Is unable to interrupt aspirin or other NSAIDs, other than aspirin dose ≤1.3 g/day for a 5-day period 5) Is unable or unwilling to take folic acid or vitamin B12 supplementation, and 6) has a known hypersensitivity to carboplatin or pemetrexed, or any of their excipients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03918278


Locations
Layout table for location information
United States, Michigan
Henry Ford Health System ( Site 0002)
Detroit, Michigan, United States, 48202
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0003)
Hackensack, New Jersey, United States, 07601
United States, Texas
Next Oncology ( Site 0001)
San Antonio, Texas, United States, 78229
Australia, New South Wales
Macquarie University ( Site 0033)
Macquarie University, New South Wales, Australia, 2109
Australia, Victoria
Alfred Health ( Site 0031)
Melbourne, Victoria, Australia, 3004
Canada, British Columbia
BC Cancer - Vancouver Center ( Site 0010)
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Princess Margaret Cancer Centre ( Site 0011)
Toronto, Ontario, Canada, M5G 2M9
Chile
FALP-UIDO ( Site 0100)
Santiago, Region M. De Santiago, Chile, 6900941
Bradfordhill-Clinical Area ( Site 0101)
Santiago, Region M. De Santiago, Chile, 8420383
Israel
Hadassa Ein Karem Medical Center ( Site 0022)
Jerusalem, Israel, 9112001
Chaim Sheba Medical Center ( Site 0020)
Ramat Gan, Israel, 5265601
Italy
ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 0091)
Siena, Toscana, Italy, 53100
Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (
Milano, Italy, 20141
Korea, Republic of
Seoul National University Hospital ( Site 0061)
Seoul, Korea, Republic of, 03080
Asan Medical Center ( Site 0060)
Seoul, Korea, Republic of, 05505
Spain
Hospital Clinic i Provincial ( Site 0041)
Barcelona, Spain, 08036
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
Additional Information:
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT03918278    
Other Study ID Numbers: 0482-001
MK-0482-001 ( Other Identifier: Merck )
2020-004089-20 ( EudraCT Number )
First Posted: April 17, 2019    Key Record Dates
Last Update Posted: May 25, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Gemcitabine
Pembrolizumab
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors