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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04700072
Registration number
NCT04700072
Ethics application status
Date submitted
5/01/2021
Date registered
7/01/2021
Date last updated
22/12/2023
Titles & IDs
Public title
Substudy 02D: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Melanoma Brain Metastasis (MK-3475-02D/KEYMAKER-U02)
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Scientific title
A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02D
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Secondary ID [1]
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MK-3475-02D
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Secondary ID [2]
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3475-02D
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Other interventions - Pembrolizumab/Quavonlimab
Treatment: Drugs - Lenvatinib
Experimental: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib - Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab and quavonlimab) intravenously (IV) plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
Experimental: Pembrolizumab + Lenvatinib - Participants will receive pembrolizumab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
Other interventions: Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Other interventions: Pembrolizumab/Quavonlimab
Administered via IV infusion at a specified dose on specified days
Treatment: Drugs: Lenvatinib
Administered via oral capsule at a specified dose on specified days
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Intervention code [1]
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Other interventions
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of participants who experience an adverse event (AE)
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Assessment method [1]
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.
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Timepoint [1]
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Up to ~28 months
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Primary outcome [2]
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Percentage of participants who discontinue study treatment due to an AE
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Assessment method [2]
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.
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Timepoint [2]
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Up to ~24 months
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Primary outcome [3]
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Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
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Assessment method [3]
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ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at =30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
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Timepoint [3]
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Up to ~30 months
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Secondary outcome [1]
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Duration of Response (DOR) per RECIST 1.1
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Assessment method [1]
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For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented CR or PR until 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 =1 new lesion is also considered PD. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
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Timepoint [1]
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Up to ~30 months
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Secondary outcome [2]
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Brain metastasis response rate (BMRR) per Response Assessment in Neuro- Oncology Brain Metastases (RANO-BM)
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Assessment method [2]
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BMRR is defined as the percentage of participants in the analysis population who achieve a confirmed intracranial CR (disappearance of all lesions, no usage of corticosteroids and stable or improved clinical status) or PR (=30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters, no progression of non-target lesions or new lesions, stable or decreased corticosteroid use, or stable or improved clinical status). Responses are according to RANO-BM as assessed by BICR. RANO-BM uses a combination of RECIST 1.1 and clinical data to assess response to treatment in brain metastases.
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Timepoint [2]
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Up to ~30 months
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Secondary outcome [3]
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Brain metastasis duration of response (BM-DOR) per RANO-BM
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Assessment method [3]
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For participants in the analysis population who demonstrate a confirmed intracranial CR (disappearance of all lesions, no usage of corticosteroids, stable or improved clinical status) or PR (=30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters, no progression of non-target lesions or new lesions, stable or decreased corticosteroid use, or stable or improved clinical status), DOR is defined as the time from first documented CR or PR until PD or death due to any cause, whichever occurs first. Per RANO-BM, PD is defined as =20% increase in the sum of diameters of target lesions and an absolute increase of =5 mm in =1 lesion. Unequivocal increase in non-target lesions, the appearance of =1 new lesion or worsening of clinical status is also considered PD. Responses are according to RANO-BM as assessed by BICR. RANO-BM uses a combination of RECIST 1.1 and clinical data to assess response to treatment in brain metastases.
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Timepoint [3]
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Up to ~30 months
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Secondary outcome [4]
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Progression-free survival (PFS) per RECIST 1.1
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Assessment method [4]
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PFS is defined as the time from randomization to the first documented 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. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
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Timepoint [4]
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Up to ~30 months
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Eligibility
Key inclusion criteria
- Has American Joint Committee on Cancer (AJCC) Stage IV, M1D melanoma
- Is neurologically asymptomatic from brain metastases and has not received systemic
corticosteroid therapy in the 10 days prior to beginning study intervention
- If capable of producing sperm, male participants agree to the following during the
intervention period and for at least the time needed to eliminate each study
intervention after the last dose of study intervention. The length of time required to
continue contraception for each study intervention is:
- Lenvatinib: 7 days
- Abstains from penile-vaginal intercourse as their preferred and usual lifestyle
(abstinent on a long-term and persistent basis) and agrees to remain abstinent. OR
- Uses contraception unless confirmed to be azoospermic
- Female participants are not pregnant or breastfeeding and are either not a woman of
child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective
or are abstinent from heterosexual intercourse during the intervention period and for
at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab,
or 30 days after the last dose of lenvatinib, whichever occurs last
- Has adequate organ function
- Female participants agree to abstain from breastfeeding during the study intervention
period and for at least the time needed to eliminate study intervention after the last
dose of study intervention. The length of time required for each study intervention
is:
- MK-1308A: 120 days
- MK-3475: 120 days
- Lenvatinib: 30 days
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Minimum age
18
Years
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Maximum age
120
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within
10 days before the first dose of study intervention
- Has current or history of known leptomeningeal involvement
- Has received stereotactic or highly conformal radiotherapy within 2 weeks before the
start of dosing
- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the
first dose of study drug
- Has untreated or unresolved intracranial hemorrhage from central nervous system (CNS)
metastasis
- Has an active infection requiring systemic therapy
- Has a known additional malignancy that is progressing or requires active treatment
within the past 2 years
- Has ocular melanoma
- Has an active autoimmune disease that has required systemic treatment in the past 2
years
- Has known history of immunodeficiency virus (HIV)
- Has known history of hepatitis B or known hepatitis C virus
- Has a history of (noninfectious) pneumonitis that required steroids or current
pneumonitis
- Has received prior systemic anticancer therapy within 4 weeks prior to
randomization/allocation
- Has a history of whole brain irradiation
- Has received prior radiotherapy within 2 weeks of first dose of study intervention
- Has had major surgery <3 weeks prior to first dose of study intervention
- Has received a live or live attenuated vaccine within 30 days prior to the first dose
of study intervention
- Has had an allogeneic tissue/solid organ transplant
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
3/05/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
3/04/2030
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Actual
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Sample size
Target
300
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW
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Recruitment hospital [1]
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Calvary Mater Newcastle ( Site 4404) - Waratah
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Recruitment hospital [2]
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Melanoma Institute Australia ( Site 4402) - Wollstonecraft
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Recruitment postcode(s) [1]
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2298 - Waratah
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Recruitment postcode(s) [2]
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2065 - Wollstonecraft
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Colorado
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United States of America
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State/province [3]
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Maryland
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Country [4]
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United States of America
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State/province [4]
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New York
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Country [5]
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United States of America
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State/province [5]
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North Carolina
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Country [6]
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United States of America
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State/province [6]
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Ohio
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Country [7]
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United States of America
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State/province [7]
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Virginia
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Country [8]
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France
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State/province [8]
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Bouches-du-Rhone
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Country [9]
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France
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State/province [9]
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Gironde
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Country [10]
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France
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State/province [10]
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Haute-Garonne
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Country [11]
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France
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State/province [11]
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Ile-de-France
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Country [12]
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France
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Rhone
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Country [13]
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France
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State/province [13]
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Paris
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Israel
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State/province [14]
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Afula
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Israel
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Haifa
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Country [16]
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Israel
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State/province [16]
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Jerusalem
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Israel
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Petah-Tikva
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Israel
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Ramat Gan
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Italy
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Milano
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Italy
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Napoli
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Italy
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Padova
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Italy
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Siena
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South Africa
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Eastern Cape
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South Africa
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Gauteng
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South Africa
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Western Cape
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Spain
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Cataluna
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Spain
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State/province [27]
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Madrid, Comunidad De
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Switzerland
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Geneve
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Switzerland
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Vaud
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Switzerland
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State/province [30]
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Zurich
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Merck Sharp & Dohme LLC
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
Substudy 02D is part of a larger research study that is testing experimental treatments for
melanoma, a type of skin cancer. The larger study is the umbrella study.
The goal of substudy 02D is to evaluate the safety and efficacy of investigational treatment
arms in programmed cell-death 1 (PD-1) naïve or PD-1 exposed participants with melanoma brain
metastasis (MBM) and to identify the investigational agent(s) that, when used in combination,
are superior to the current treatment options/historical control available.
As of amendment 2 (effective 01DEC2022) enrollment into the treatment arm of pembrolizumab
and lenvatinib has been discontinued.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04700072
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Medical Director
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Address
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Merck Sharp & Dohme LLC
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04700072
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