Advanced MelanomaPhase 2NCT03407170

Immunologic Determinants of Response to Pembrolizumab (MK-3475) in Advanced Melanoma (MK-3475-161/KEYNOTE-161)

A Phase 2 study testing pembrolizumab in people with Advanced Melanoma, run by Merck Sharp & Dohme LLC at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

In this study, participants with advanced melanoma will be treated with pembrolizumab (MK-3475) and their tumors and blood will be analyzed for changes related to pembrolizumab therapy. The primary hypotheses are that participants who respond to pembrolizumab have: 1. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Melanoma
What is being tested?: pembrolizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1 participants
Where: 2 sitesUnited States
Study dates: 28 Jun 2018to 14 Aug 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Has a histologically confirmed diagnosis of unresectable stage III or metastatic melanoma not amenable to local therapy
Has testing for a BRAF mutation prior to study entry
Has measurable disease per RECIST 1.1 as assessed by the investigator/radiology
Has resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If the participant received major surgery or radiation therapy of >30 Gray units, they must have recovered from the toxicity and/or complications from the intervention
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days of study start
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and agrees to use a contraceptive method, consistent with local regulations regarding the methods of contraception for those participating in clinical studies, during the treatment period and for at least 120 days after the last dose of study treatment
A male participant is eligible to participate if he agrees not to donate sperm PLUS to be abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, consistent with local regulations regarding the methods of contraception for those participating in clinical studies, during the treatment period and for at least 120 days after the last dose of study treatment

Who cannot join

Has disease that is suitable for local therapy administered with curative intent
Has a history of interstitial lung disease
Has a positive pregnancy test within 72 hours before the first dose of study therapy
Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study start
Has received prior radiotherapy within 2 weeks of start of study therapy

Show all 21Show fewer

Has received a live vaccine within 30 days prior to the first dose of study therapy
Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony stimulating factor [GMCSF] or recombinant erythropoietin) within 4 weeks prior to study start
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study therapy
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 therapy
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of basal cell and squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
Is pregnant or breastfeeding or expecting to conceive or father children starting with the screening visit through 120 days after the last dose of study therapy

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Massachusetts General Hospital ( Site 0102)
Boston, Massachusetts, 02114
Dana Farber Cancer Institute ( Site 0101)
Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: An Open-Label, Phase II Study to Determine the Immunologic Correlates of Pembrolizumab-Mediated Tumor Regression in Subjects With Advanced Melanoma (KEYNOTE-161)

In this study, participants with advanced melanoma will be treated with pembrolizumab (MK-3475) and their tumors and blood will be analyzed for changes related to pembrolizumab therapy.

The primary hypotheses are that participants who respond to pembrolizumab have:

a higher fraction of cytotoxic tumor-infiltrating T-lymphocytes (FCT) at baseline compared to those who do not respond to pembrolizumab
a higher fold-increase in FCT compared to baseline than those who do not respond to pembrolizumab
a higher Average Specific Cytotoxic T-lymphocyte Frequency Ratio (ASCTFR) compared to those who do not respond to pembrolizumab

Conditions: Advanced Melanoma
Being tested: pembrolizumab
Keywords: Programmed Cell Death-1 (PD-1), PD1, Programmed Cell Death-Ligand 1 (PD-L1), Programmed Cell Death-Ligand 2 (PD-L2), PDL1, PDL2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

pembrolizumabBiological
Also called KEYTRUDA®, MK-3475
200 mg by IV infusion Q3W for up to 24 months

Study groups in NCT03407170
Study group	Role	What they receive
Pembrolizumab	Experimental	Participants receive pembrolizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) for up to 24 months Receives: Biological: pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Fraction of Cytotoxic T-lymphocytes (FCT) for Participants With Response Versus Participants With Progression
FCT is defined as the fraction of CD8+ T-cells expressing a predefined single-cell ribonucleic acid (RNA) gene signature to the total tumor infiltrating CD8+T-cells isolated from tumor biopsies.
Measured: Up to approximately 59 weeks
Average Specific Cytotoxic T-lymphocyte Frequency Ratio (ASCTFR) for Participants With Response Versus Participants With Progression
ASCTFR is defined as the arithmetic average of the log10 ratio of the frequency of individual specific cytotoxic T-Cell Receptor (TCR) clones of on-treatment to pre-treatment.
Measured: Up to approximately 59 weeks
Change in Baseline of Fraction of Cytotoxic T-lymphocytes (FCT) for Participants With Response Versus Participants With Progression
The fold change from baseline in FCT. FCT is defined as the fraction of CD8+ T-cells expressing a predefined single-cell RNA gene signature to the total tumor infiltrating CD8+T-cells isolated from tumor biopsies.
Measured: Up to approximately 59 weeks

Secondary outcomes (7)

Number of Participants Who Experienced an Adverse Event (AE)
An AE is 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 experienced an AE is presented.
Measured: Up to approximately 59 weeks
Number of Participants Who Discontinued Any Study Drug Due to an Adverse Event (AE)
The number of participants who discontinued any study treatment due to an AE is presented.
Measured: Up to approximately 59 weeks
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
ORR is defined as the percentage of participants in the analysis population who have 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 Version 1.1 as assessed by the investigator.
Measured: Up to approximately 59 weeks
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS is defined as the time from start of treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first, per RECIST Version 1.1 as assessed by the investigator.
Measured: Up to approximately 59 weeks
Overall Survival (OS)
OS is defined as the time from the start of treatment to death due to any cause.
Measured: Up to approximately 59 weeks
Neoepitope Burden
Neoepitope sequencing will be generated based on single cell ribonucleic acid (RNA) sequencing (scRNAseq), whole exome sequencing, and an epitope prediction algorithm to obtain neoepitope burden.
Measured: Up to approximately 59 weeks
Antigenic Determinants of Highly-functional CD8 + T-cell Clones
T-cell receptors (TCRs) from CD8+ T-cell clones will be identified by single cell ribonucleic acid (RNA) sequencing (scRNAseq) and their killing function will be confirmed by TCR-transduced T-cells recognizing autologous tumor-derived cell lines.
Measured: Up to approximately 59 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jun 201814 Aug 2019

First posted23 Jan 2018
Study start28 Jun 2018
Primary completion14 Aug 2019
Study completion14 Aug 2019

Why it stopped: Lack of Accrual

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Advanced MelanomaStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 1 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03407170
Sponsor's protocol ID: 3475-161
Other IDs: MK-3475-161, KEYNOTE-161
Status last verified: Jun 2020
First submitted: 18 Jan 2018
Last updated: 15 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
Melanoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 2
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Metastatic Melanoma, Advanced Locoregional Melanoma

All Advanced Melanoma trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Phase II Study to Determine the Immunologic Correlates of Pembrolizumab-Mediated Tumor Regression in Subjects With Advanced Melanoma (KEYNOTE-161)
ClinicalTrials.gov ID: NCT03407170
Acronym / sponsor ID: 3475-161
Conditions: Advanced Melanoma
Keywords: Programmed Cell Death-1 (PD-1), PD1, Programmed Cell Death-Ligand 1 (PD-L1), Programmed Cell Death-Ligand 2 (PD-L2), PDL1, PDL2
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Lack of Accrual
Enrolment: 1 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 28 Jun 2018 (actual)
Primary completion: 14 Aug 2019 (actual)
Study completion: 14 Aug 2019 (actual)
First posted: 23 Jan 2018 (actual)
Results: Posted 15 Jul 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

In this study, participants with advanced melanoma will be treated with pembrolizumab (MK-3475) and their tumors and blood will be analyzed for changes related to pembrolizumab therapy.

The primary hypotheses are that participants who respond to pembrolizumab have:

a higher fraction of cytotoxic tumor-infiltrating T-lymphocytes (FCT) at baseline compared to those who do not respond to pembrolizumab
a higher fold-increase in FCT compared to baseline than those who do not respond to pembrolizumab
a higher Average Specific Cytotoxic T-lymphocyte Frequency Ratio (ASCTFR) compared to those who do not respond to pembrolizumab

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Pembrolizumab	Experimental	Biological: pembrolizumabParticipants receive pembrolizumab 200 mg by intravenous (IV) infusion every 3 weeks (Q3W) for up to 24 months

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Has a histologically confirmed diagnosis of unresectable stage III or metastatic melanoma not amenable to local therapy
Has testing for a BRAF mutation prior to study entry
Has measurable disease per RECIST 1.1 as assessed by the investigator/radiology
Has resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If the participant received major surgery or radiation therapy of >30 Gray units, they must have recovered from the toxicity and/or complications from the intervention
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days of study start

Key exclusion criteria (21 listed)

Has disease that is suitable for local therapy administered with curative intent
Has a history of interstitial lung disease
Has a positive pregnancy test within 72 hours before the first dose of study therapy
Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study start

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
pembrolizumabAlso: KEYTRUDA®, MK-3475200 mg by IV infusion Q3W for up to 24 months	Biological	Pembrolizumab

Primary outcome

Mean Fraction of Cytotoxic T-lymphocytes (FCT) for Participants With Response Versus Participants With Progression
Time frame: Up to approximately 59 weeks
FCT is defined as the fraction of CD8+ T-cells expressing a predefined single-cell ribonucleic acid (RNA) gene signature to the total tumor infiltrating CD8+T-cells isolated from tumor biopsies.
Average Specific Cytotoxic T-lymphocyte Frequency Ratio (ASCTFR) for Participants With Response Versus Participants With Progression
Time frame: Up to approximately 59 weeks
ASCTFR is defined as the arithmetic average of the log10 ratio of the frequency of individual specific cytotoxic T-Cell Receptor (TCR) clones of on-treatment to pre-treatment.
Change in Baseline of Fraction of Cytotoxic T-lymphocytes (FCT) for Participants With Response Versus Participants With Progression
Time frame: Up to approximately 59 weeks
The fold change from baseline in FCT. FCT is defined as the fraction of CD8+ T-cells expressing a predefined single-cell RNA gene signature to the total tumor infiltrating CD8+T-cells isolated from tumor biopsies.

7 secondary outcomes

Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 59 weeks
Number of Participants Who Discontinued Any Study Drug Due to an Adverse Event (AE)
Time frame: Up to approximately 59 weeks
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: Up to approximately 59 weeks
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: Up to approximately 59 weeks
Overall Survival (OS)
Time frame: Up to approximately 59 weeks
Neoepitope Burden
Time frame: Up to approximately 59 weeks
Antigenic Determinants of Highly-functional CD8 + T-cell Clones
Time frame: Up to approximately 59 weeks

Results and safety

Results posted to the registry on 15 Jul 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pembrolizumab	1	0

Primary outcome: Mean Fraction of Cytotoxic T-lymphocytes (FCT) for Participants With Response Versus Participants With Progression

Time frame: Up to approximately 59 weeks

Population analysed: No data were collected or analyzed for this outcome measure due to early termination of the study.

Primary outcome: Average Specific Cytotoxic T-lymphocyte Frequency Ratio (ASCTFR) for Participants With Response Versus Participants With Progression

Time frame: Up to approximately 59 weeks

Population analysed: No data were collected or analyzed for this outcome measure due to early termination of the study.

Primary outcome: Change in Baseline of Fraction of Cytotoxic T-lymphocytes (FCT) for Participants With Response Versus Participants With Progression

Time frame: Up to approximately 59 weeks

Population analysed: No data were collected or analyzed for this outcome measure due to early termination of the study.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to approximately 59 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pembrolizumab	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): Study was stopped early due to lack of accrual.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Advanced Melanoma

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
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RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
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RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 2
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Metastatic Melanoma, Advanced Locoregional Melanoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pembrolizumab in people with Advanced Melanoma, run by Merck Sharp & Dohme LLC at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Fraction of Cytotoxic T-lymphocytes (FCT) for Participants With Response Versus Participants With Progression (time frame: Up to approximately 59 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03407170.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2020.