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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03564691




Registration number
NCT03564691
Ethics application status
Date submitted
11/06/2018
Date registered
21/06/2018

Titles & IDs
Public title
Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4830-001)
Scientific title
A Phase 1 Open Label, Multi-Arm, Multicenter Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab for Participants With Advanced Solid Tumors
Secondary ID [1] 0 0
MK-4830-001
Secondary ID [2] 0 0
4830-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MK-4830
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Carboplatin
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Lenvatinib
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Cisplatin
Treatment: Other - MK-4830A

Experimental: Dose Escalation, Part A: MK-4830 Monotherapy - MK-4830 monotherapy (with MK-4830 doses determined by an accelerated titration design \[ATD\]) will be administered intravenously (IV), every 3 weeks (Q3W), starting with Cycle 1, Day 1, for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Participants enroll with histologically or cytologically confirmed pancreatic adenocarcinoma.

Experimental: Dose Escalation, Part B: MK-4830 Monotherapy - MK-4830 monotherapy (with MK 4830 doses determined by a modified toxicity probability interval \[mTPI\] method) will be administered IV, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Participants enroll with histologically or cytologically confirmed pleural or peritoneal malignant mesothelioma, epithelial, sarcomatoid, or biphasic subtypes.

Experimental: Dose Escalation, Part C: MK-4830 and Pembrolizumab - Combination therapy with MK-4830 and pembrolizumab (with MK-4830 doses determined by an mTPI design). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Experimental: Dose Expansion, Arm A: Pancreatic Adenocarcinoma - Combination therapy with the preliminary recommended phase 2 dose (RP2D) A of MK-4830, and pembrolizumab, in participants with histologically or cytologically confirmed pancreatic adenocarcinoma. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Experimental: Dose Expansion, Arm B: Glioblastoma (GBM) - Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants with histologically or cytologically confirmed GBM. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Experimental: Dose Expansion, Arm C: R/M HNSCC - Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically or cytologically-confirmed recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) whose disease progressed on an anti-programmed cell death 1/programmed cell death ligand 1 (PD1/L1) therapy. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Experimental: Dose Expansion, Arm D: PD-L1 positive HNSCC, Dose A - Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically or cytologically-confirmed advanced programmed death-ligand 1 (PD-L1) positive head and neck squamous cell carcinoma (HNSCC). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Experimental: Dose Expansion, Arm E: First-Line Advanced NSCLC, Dose A - Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically-confirmed, first-line treatment advanced non-small-cell-lung-cancer (NSCLC) (Stage IIIB or IV). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Experimental: Dose Expansion, Arm F: First-Line Advanced NSCLC, Dose B - Combination therapy with the preliminary RP2D B of MK-4830, and pembrolizumab, in participants who have histologically-confirmed, first-line treatment advanced non-small-cell-lung-cancer (NSCLC) (Stage IIIB or IV). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Experimental: Dose Expansion, Arm G: NSCLC, +Carboplatin/Pemetrexed - Combination therapy with the preliminary RP2D A of MK-4830, pembrolizumab, and carboplatin/pemetrexed in participants with advanced non-squamous non-small-cell-lung-cancer (NSCLC) (Stage IIIB or IV). MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles. Carboplatin and pemetrexed will be administered IV Q3W, starting with Cycle 1, Day 1, for 4 cycles, followed by pemetrexed Q3W continuous with MK-4830 and pembrolizumab, up to 35 cycles. Each cycle is 21 days (up to approximately 2 years).

Experimental: Dose Expansion, Arm H: RCC, +Lenvatinib - Combination therapy with the preliminary RP2D A of MK-4830, pembrolizumab, and lenvatinib in participants with advanced renal cell carcinoma (RCC). MK-4830 will be administered IV, Q3W, starting with Cycle 1 following pembrolizumab infusion, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years). Lenvatinib will be administered orally once daily for up to 35 cycles of 21 days (up to approximately 2 years).

Experimental: Dose Expansion, Arm I: R/M Gastric/GE Junction Adenocarcinoma - Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in participants who have histologically or cytologically-confirmed recurrent or metastatic (R/M) gastric or gastroesophageal (GE) junction adenocarcinoma and who have been previously treated with at least 2 prior lines of therapy. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Experimental: Dose Expansion, Arm J: Ovarian Cancer - Triple combination therapy with pembrolizumab plus preliminary RP2D A of MK-4830 plus paclitaxel in participants who have histologically confirmed, ovarian cancer. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1 for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Paclitaxel will be administered by IV, once every week (QW) on Days 1, 8, and 15 of each 21-day cycle until disease progression or prohibitive toxicity.

Experimental: Dose Expansion, Arm K: Triple negative Breast Cancer (TNBC) - Triple combination therapy with pembrolizumab plus preliminary RP2D A of MK-4830 plus paclitaxel in participants who have histologically confirmed TNBC. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1 for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Paclitaxel will be administered by IV on Days 1, 8, and 15 every 4 weeks (Q4W) until disease progression or prohibitive toxicity.

Experimental: Dose Expansion, Arm L: Mesothelioma - Triple combination therapy with pembrolizumab plus preliminary RP2D A of MK-4830 plus pemetrexed plus cisplatin in participants who have histologically confirmed advanced mesothelioma. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1 for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days. Pemetrexed will be administered by IV, on Day 1 of each Q3W cycle for a maximum of 6 cycles. Each cycle is 21 days. Cisplatin will be administered by IV, on Day 1 of each Q3W cycle for a maximum of 6 cycles. Each cycle is 21 days.

Experimental: Dose Expansion, Arm M: Advanced Solid Tumor in Chinese Participants In China - Combination therapy with the preliminary RP2D A of MK-4830, and pembrolizumab, in Chinese participants, who reside in China, have histologically or cytologically-confirmed advanced/metastatic solid tumor, and who have been previously treated with at least 2 prior lines of therapy. MK-4830 will be administered IV following pembrolizumab infusion, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles. Each cycle is 21 days. Pembrolizumab will be administered by IV, Q3W, starting with Cycle 1, Day 1. Each cycle is 21 days. The combination may be administered for a maximum of 35 cycles (up to approximately 2 years).

Experimental: Coformulation Phase, Arm N: MK-4830A (Coformulation of MK-4830 + pembrolizumab) - Monotherapy with MK-4830A, a coformulation of MK-4830 800 mg + pembrolizumab 200 mg, in participants with histologically or cytologically-confirmed advanced/metastatic solid tumor, and who and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit. MK-4830A will be administered IV, Q3W, starting with Cycle 1, Day 1, for a maximum of 35 cycles (up to approximately 2 years). Each cycle is 21 days.


Treatment: Drugs: MK-4830
MK-4830 will be administered intravenously (IV) Q3W. In Part C, MK-4830 will be administered after completion of pembrolizumab infusion. Dose escalation will proceed based on emerging safety and tolerability data of MK-4830 as monotherapy (Part A and B) and as combination therapy with pembrolizumab (Part C). For each dose level, an assessment will be made of the safety and tolerability data in order to define the next dose level to be tested.

Treatment: Drugs: Pembrolizumab
Pembrolizumab will be administered at 200 mg IV Q3W.

Treatment: Drugs: Carboplatin
Carboplatin will be administered IV Q3W.

Treatment: Drugs: Pemetrexed
Pemetrexed will be administered IV Q3W.

Treatment: Drugs: Lenvatinib
Lenvatinib will be administered orally once daily.

Treatment: Drugs: Paclitaxel
Paclitaxel will be administered IV QW on Days 1, 8, and 15 of each 21-day cycle until disease progression or prohibitive toxicity (Arm J) and on Days 1, 8, and 15 Q4W until disease progression or prohibitive toxicity (Arm K).

Treatment: Drugs: Cisplatin
Cisplatin will be administered IV Q3W.

Treatment: Other: MK-4830A
MK-4830A, a coformulation of MK-4830 800 mg + pembrolizumab 200 mg, will be administered IV Q3W.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Cycle 1 (Up to 21 days)
Primary outcome [2] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [2] 0 0
Up to approximately 27 months
Primary outcome [3] 0 0
Number of Participants Who Discontinued Study Treatment Due to an AE
Timepoint [3] 0 0
Up to approximately 24 months
Primary outcome [4] 0 0
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Response Assessment in Neuro-Oncology (RANO) as Assessed by Investigator
Timepoint [4] 0 0
Up to approximately 24 months
Primary outcome [5] 0 0
ORR per Modified RECIST (mRECIST) 1.1 as Assessed by Investigator
Timepoint [5] 0 0
Up to approximately 24 months
Secondary outcome [1] 0 0
Area Under the Curve (AUC) of Plasma MK-4830
Timepoint [1] 0 0
At designated time points detailed in Description (Up to approximately 25 months)
Secondary outcome [2] 0 0
Minimum Concentration Between Doses (Ctrough) of Plasma MK-4830
Timepoint [2] 0 0
At designated time points detailed in Description (Up to approximately 25 months)
Secondary outcome [3] 0 0
Maximum Drug Concentration (Cmax) of Plasma MK-4830
Timepoint [3] 0 0
At designated time points detailed in Description (Up to approximately 25 months)
Secondary outcome [4] 0 0
Number of Participants Positive for Anti-Drug Antibodies (ADA) After MK-4830 plus Pembrolizumab Treatment
Timepoint [4] 0 0
At designated time points (Up to approximately 25 months)
Secondary outcome [5] 0 0
Minimum Concentration Between Doses (Ctrough) of Plasma Pembrolizumab in Arm M
Timepoint [5] 0 0
At designated time points detailed in Description (Up to approximately 25 months)
Secondary outcome [6] 0 0
Maximum Drug Concentration (Cmax) of Plasma Pembrolizumab in Arm M
Timepoint [6] 0 0
At designated time points detailed in Description (Up to approximately 25 months)

Eligibility
Key inclusion criteria
* Dose escalation participants: Has any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and has received, has been intolerant to, or has been ineligible for all treatment known to confer clinical benefit. Solid tumors of any type are eligible for enrollment
* Has measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1), Response Assessment in Neuro-Oncology (RANO), or modified RECIST (mRECIST) as assessed by the local site investigator/radiology
* Submits an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample). This inclusion criterion does not apply to Expansion phase Arm M
* Dose Escalation Part C and Back-fill participants: Has 1 or more discrete malignant lesions that are amenable to biopsy
* Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. This inclusion criterion does not apply to Expansion phase Arm B
* Demonstrates adequate organ function
* A male participant must agree to use an approved contraception(s) during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period
* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either not a woman of childbearing potential (WOCBP) OR if a WOCBP agrees to follow the study contraceptive guidance during the treatment period and for at least 180 days after the last dose of study treatment
* Expansion phase Arm A participants:

* Has histologically or cytologically confirmed metastatic pancreatic adenocarcinoma
* Received at least 1 prior line of therapy and no more than 3 prior lines of systemic therapy
* Expansion phase Arm B participants:

* Has histologically or cytologically confirmed unresectable glioblastoma multiforme (GBM) or its variants
* Has a Karnofsky performance status (KPS) = 70
* Has had no more than 1 prior line of therapy for GBM. Radiation with or without chemotherapy is acceptable as the prior treatment
* Has shown unequivocal evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan by contrast within 2 weeks prior to randomization
* Has an interval of at least 3 weeks (to randomization) between prior surgical resection (one week for stereotactic biopsy)
* Has an interval of at least 12 weeks from the completion of radiation therapy to randomization unless there is unequivocal histologic confirmation of tumor progression or radiographic progression outside of the prior radiation field
* Is neurologically stable (eg, without a progression of neurologic symptoms or requiring escalating doses of systemic steroid therapy within last 2 weeks) and clinically stable
* Expansion phase Arm C participants:

* Has histologically confirmed recurrent or metastatic head and neck squamous cell cancer (HNSCC) of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
* Has experienced disease progression at any time during or after treatment with a platinum-containing (eg, carboplatin or cisplatin) regimen with or without cetuximab
* Expansion phase Arm D participants:

* Has histologically confirmed advanced or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
* Has not had any prior programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) therapy
* Expansion phase Arms E and F participants:

* Has a histologically or cytologically confirmed diagnosis of advanced (Stage IIIb) or Stage IV metastatic non-small-cell lung cancer (NSCLC)
* Has received no prior systemic therapy for chemotherapy or other targeted or biological antineoplastic therapy treatment for Stage IIIb or Stage IV metastatic NSCLC. Treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed if therapy was completed at least 6 months prior to the diagnosis of advanced disease. Participants with prior treatment with an anti-PD-1 or PD-L1 agent are not eligible
* Expansion phase Arm G participants:

* Has a histologically or cytologically confirmed diagnosis of advanced (Stage IIIb) or Stage IV metastatic nonsquamous NSCLC (American Joint Committee on Cancer (AJCC) version 8)
* Is able to tolerate chemotherapy with carboplatin and pemetrexed
* Has received no prior systemic therapy for advanced NSCLC
* Expansion phase Arm H participants:

* Has histologically confirmed diagnosis of renal cell cancer (RCC) with clear cell component with or without sarcomatoid features
* Has locally advanced/metastatic disease or has recurrent disease
* May have received 1 or 2 prior lines of systemic therapy for advanced RCC
* Expansion phase Arm I participants:

* Has histologically confirmed diagnosis of recurrent and/or metastatic gastric or gastroesophageal junction adenocarcinoma that is considered incurable by local therapies
* Has received and progressed on at least two prior chemotherapy regimens
* If tumor was if human epidermal growth factor receptor 2 (HER2/neu) positive, participant must have previously received treatment with trastuzumab
* Expansion phase Arm J participants

* Has histologically confirmed high-grade epithelial ovarian, fallopian tube or primary peritoneal carcinoma
* Has received 1 or 2 prior lines of systemic therapy, including at least 1 prior platinum-based therapy
* Has radiographic evidence of disease progression
* Is a candidate for paclitaxel chemotherapy
* Expansion phase Arm K participants:

* Has locally recurrent inoperable breast cancer OR have metastatic breast cancer not previously treated
* Has confirmed triple-negative breast cancer (TNBC)
* Has completed treatment for Stage I-III breast cancer, if indicated, and =6 months elapsed between the completion of treatment and first documented local or distant disease recurrence
* Has been treated with (neo)adjuvant anthracycline
* Expansion phase Arm L participants:

* Has histologically confirmed diagnosis of recurrent and/or advanced mesothelioma that is considered incurable by standard therapies
* Is eligible to receive standard chemotherapy
* Expansion phase Arm M participants

* Has any histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant of, been ineligible for, or refused all treatment known to confer clinical benefit
* Has received up to 2 prior systemic regimens for the treatment of advanced/metastatic solid tumor
* Is a Chinese participant residing in China
* Coformulation Arm N participants

* Has any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier
* Has not recovered from all radiation-related toxicities to Grade 1 or less, requires corticosteroids, and had radiation pneumonitis
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
* Has known untreated central nervous system metastases or known carcinomatous meningitis. This exclusion criterion does not apply to Expansion phase Arm B
* Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related AEs
* Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of pembrolizumab and/or chemotherapy agents
* Has an active infection requiring therapy
* Has a history or current interstitial lung disease
* Has a history of noninfectious pneumonitis that required steroids or current pneumonitis
* Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy
* Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure
* Has a known history of human immunodeficiency virus (HIV)
* Has a known active hepatitis B or C
* Is taking chronic systemic steroids in doses >10 mg daily of prednisone or equivalent within 7 days prior to the first dose of trial treatment
* Has not fully recovered from any effects of major surgery without significant detectable infection. Surgical proceduress that required general anesthesia must be completed at least 2 weeks before first study treatment administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study treatment administration and participants should be recovered
* Has received a live or live-attenuated virus vaccine within 30 days prior to first dose of study intervention
* Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of MK-4830
* All Expansion phase participants:

* Tumor types with known MSI-high status are not eligible
* Expansion phase Arm A participants:

* Has received more than 3 lines of prior therapy for advanced disease (pancreatic cancer)
* Expansion phase Arm B participants:

* Has tumor primarily localized to the brainstem or spinal cord
* Has presence of diffuse leptomeningeal disease or extracranial disease
* Has recurrent tumor greater than 6 cm in maximum diameter
* Requires treatment with moderate or high dose systemic corticosteroids for at least 3 days within 2 weeks of randomization
* Expansion phase Arm D participants:

* Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy treatment for their advanced metastatic HNSCC
* Expansion phase Arm E and F participants:

* Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy treatment for their Stage IIIb or Stage IV metastatic NSCLC
* Has had prior treatment with any anti-PD-1, PD-L1, or programmed cell death-ligand 2 (PD-L2) agent
* Expansion phase Arm G participants:

* Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy treatment for their Stage IIIb or Stage IV nonsquamous NSCLC
* Has had prior treatment with any anti-PD-1, PD-L1, or PD-L2 agent
* Expansion phase Arm H participants:

* Has a clinically significant gastrointestinal (GI) abnormality
* Has a history of untreated deep vein thrombosis or pulmonary embolism within 6 months prior to screening
* Has poorly controlled hypertension
* Has active GI bleeding
* Has evidence of inadequate wound healing
* Has active bleeding disorder or other history of significant bleeding episodes within 30 days prior to randomization
* Has hemoptysis within 6 weeks prior to randomization
* Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
* Expansion phase Arm I participants:

* Has experienced weight loss > 10 % over 2 months prior to first dose of study therapy
* Has clinical evidence of ascites
* Has peritoneal metastases
* Expansion phase Arm J participants:

* Has non-epithelial cancers, including borderline, malignant Müllerian mixed mucinous, malignant Brenner's tumor and undifferentiated carcinoma and/or germ cell tumors and/or sex cord - stromal tumors
* Has received more than 2 prior lines of systemic therapy for ovarian cancer
* Expansion phase Arm K participants:

* Has a known history of hypersensitivity or allergy to the study chemotherapies and/or any of their components
* Expansion phase Arm L participants:

* Has a known history of hypersensitivity or allergy to the study chemotherapies and/or any of their components
* Is receiving any medication prohibited in combination with study chemotherapies as described in the respective product labels, unless medication was stopped within 7 days prior to randomization
* All Participants (Arms A through N)

* Has symptomatic pleural effusion (eg, cough, dyspnea, pleuritic chest pain)
* 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 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/07/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/09/2025
Actual
Sample size
Target
442
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Liverpool Hospital-Medical Oncology ( Site 0250) - Liverpool
Recruitment hospital [2] 0 0
Princess Alexandra Hospital ( Site 0253) - Brisbane
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Utah
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
China
State/province [11] 0 0
Jilin
Country [12] 0 0
China
State/province [12] 0 0
Shanghai
Country [13] 0 0
China
State/province [13] 0 0
Sichuan
Country [14] 0 0
France
State/province [14] 0 0
Ile-de-France
Country [15] 0 0
France
State/province [15] 0 0
Nord
Country [16] 0 0
France
State/province [16] 0 0
Vienne
Country [17] 0 0
Greece
State/province [17] 0 0
Irakleio
Country [18] 0 0
Greece
State/province [18] 0 0
Thessaloniki
Country [19] 0 0
Israel
State/province [19] 0 0
Haifa
Country [20] 0 0
Israel
State/province [20] 0 0
Petah Tikva
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Israel
State/province [22] 0 0
Tel Aviv
Country [23] 0 0
Japan
State/province [23] 0 0
Chiba
Country [24] 0 0
Japan
State/province [24] 0 0
Tokyo
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Seoul
Country [26] 0 0
Poland
State/province [26] 0 0
Mazowieckie
Country [27] 0 0
Poland
State/province [27] 0 0
Pomorskie
Country [28] 0 0
South Africa
State/province [28] 0 0
Gauteng
Country [29] 0 0
South Africa
State/province [29] 0 0
Kwazulu-Natal
Country [30] 0 0
South Africa
State/province [30] 0 0
Western Cape
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 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
Trial website
Trial related presentations / publications
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Siu LL, Wang D, Hilton J, Geva R, Rasco D, Perets ... [More Details]


Results not provided in https://clinicaltrials.gov/study/NCT03564691