NCT02821000

Safety and Efficacy Study of Pembrolizumab (MK-3475) in Chinese Participants With Locally Advanced or Metastatic Melanoma (MK-3475-151/KEYNOTE-151)

Completed Phase 1 Results posted Last updated 30 May 2024

What this trial tests

Phase 1 trial testing Pembrolizumab in Melanoma in 103 participants. Completed in 30 November 2022.

Timeline

8 July 2016

Primary endpoint
27 December 2017

30 November 2022

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	103
Start date	8 July 2016
Primary completion	27 December 2017
Estimated completion	30 November 2022

Drugs / interventions tested

• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Melanoma — all drugs for Melanoma →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Melanoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced At Least One Adverse Event (AE) Primary · Up to approximately 17 months (Through data cutoff date of 27-December-2017)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated

Group	Value	95% CI
Pembrolizumab	101

Number of Participants Who Discontinued Study Treatment Due to an AE Primary · Up to approximately 17 months (through data cutoff date of 27-December-2017)

The number of all participants who discontinued study treatment due to an AE is presented.

Group	Value	95% CI
Pembrolizumab	4

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Primary · Up to approximately 17 months (through data cutoff date of 27-December-2017)

ORR was defined as the percentage of the participants in the analysis population who had 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 assessed by blinded independent central review (BICR). The ORR per RECIST 1.1 for participants is presented. Participants without response data were treated as non-responders. ORR was analyzed using an exact method based on binomial distribution (Clopper-Pearson method) and is reported as percentage of participants.

Group	Value	95% CI
Pembrolizumab	16.7	10.0 – 25.3

Overall Survival (OS) Secondary · Up to approximately 76 months

OS was defined as the time from first day of study treatment to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months.

Group	Value	95% CI
Pembrolizumab	13.2	10.4 – 16.5

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Secondary · Up to approximately 76 months

PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was analyz

Group	Value	95% CI
Pembrolizumab	2.8	2.7 – 3.5

Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Secondary · Up to approximately 76 months

DOR was defined as the time from first documented evidence of 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 until disease progression or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. DOR asse

Group	Value	95% CI
Pembrolizumab	13.8	5.5 – NA

Objective Response Rate (ORR) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) Secondary · Up to approximately 76 months

ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or a Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST assessed by blinded independent central review (BICR). The ORR per irRECIST for participants is presented. Participants without response data were treated as non-responders.

Group	Value	95% CI
Pembrolizumab	18.6	11.6 – 27.6

Progression-free Survival (PFS) Per Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) Secondary · Up to approximately 76 months

PFS was defined as the time from the first day of study treatment to the first documented disease progression per irRECIST based on blinded independent central review (BICR) or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumor burden confirmed by a consecutive assessment at least 4 weeks after first documentation. PFS was analyzed using the Kaplan-Meier method and is reported in months. The PFS per irRECIST for participants is presented.

Group	Value	95% CI
Pembrolizumab	2.8	2.7 – 4.0

Duration of Response (DOR) by Immune-related Response Evaluation Criteria in Solid Tumors Version (irRECIST) Secondary · Up to approximately 76 months

DOR was defined as the time from first documented evidence of Complete Response (CR: disappearance of all lesions and no new lesions confirmed by a consecutive assessment at least 4 weeks after first documentation) or Partial Response (PR: at least a 50% decrease in tumor burden relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation) per irRECIST until disease progression or death due to any cause, whichever occurred first. Using irRECIST, progressive disease was defined as at least a 25% increase in tumor burden relative the minimum recorded tumo

Group	Value	95% CI
Pembrolizumab	13.8	5.4 – NA

Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 2 (21-day Cycle) Secondary · Day 21: Prior to the Cycle 2 (21-day cycle) Dose

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 2 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 2 is presented.

Group	Value	95% CI
Pembrolizumab	8.70	± 2.4

Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 4 (21-day Cycle) Secondary · Day 63: Prior to the Cycle 4 (21-day cycle) Dose

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 4 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 4 is presented.

Group	Value	95% CI
Pembrolizumab	16.2	± 6.7

Trough Serum Concentration (Ctrough) of Pembrolizumab Prior to Cycle 6 (21-day Cycle) Secondary · Day 105: Prior to the Cycle 6 (21-day cycle) Dose

Blood samples were obtained for PK analysis of the lowest (trough) concentration of pembrolizumab prior to the next dose of pembrolizumab administered during Cycle 6 (21-day cycle). The mean Ctrough of pembrolizumab prior to Cycle 6 is presented.

Group	Value	95% CI
Pembrolizumab	22.9	± 6.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 76 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab

Serious: 13/103 (13%)

Deaths: 90/103

Pembrolizumab Second Course

Serious: 0/1 (0%)

Deaths: 0/1

Serious adverse events (15 terms)

Reaction	System	Pembrolizumab	Pembrolizumab Second Course
Arthritis	Musculoskeletal and connective tissue disorders	—	—
Sinus tachycardia	Cardiac disorders	—	—
Immune-mediated hepatitis	Hepatobiliary disorders	—	—
Bronchitis	Infections and infestations	—	—
Erysipelas	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Tumour rupture	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Cerebral haemorrhage	Nervous system disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Shock	Vascular disorders	—	—
Venous thrombosis limb	Vascular disorders	—	—

Other adverse events (58 terms — click to expand)

Reaction	System	Pembrolizumab	Pembrolizumab Second Course
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Blood bilirubin increased	Investigations	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Blood lactate dehydrogenase increased	Investigations	—	—
Fatigue	General disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Vitiligo	Skin and subcutaneous tissue disorders	—	—
Gamma-glutamyltransferase increased	Investigations	—	—
Weight decreased	Investigations	—	—
Hyperuricaemia	Metabolism and nutrition disorders	—	—
White blood cell count decreased	Investigations	—	—
Blood creatine phosphokinase increased	Investigations	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Bilirubin conjugated increased	Investigations	—	—
Neutrophil count decreased	Investigations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
White blood cell count increased	Investigations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Blood alkaline phosphatase increased	Investigations	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Insomnia	Psychiatric disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Blood cholesterol increased	Investigations	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Abdominal distension	Gastrointestinal disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—

Most-reported serious reactions: Arthritis, Sinus tachycardia, Immune-mediated hepatitis, Bronchitis, Erysipelas, Pneumonia, Rib fracture, Decreased appetite.

Data from ClinicalTrials.gov NCT02821000 adverse events section.

Sponsor's own description

The purpose of this study is to determine the safety, tolerability, and objective response rate (ORR) of pembrolizumab (MK-3475) in Chinese participants with locally advanced or metastatic melanoma, with disease progression following first line chemotherapy or targeted therapy. ORR will be based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

With Amendment 6 (effective date 18-Mar-2022), once the study objectives have been met or the study has ended, participants will be discontinued from this study and may be enrolled in an extension study to continue protocol-defined assessments and treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G₄ Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial.
   Sheng X, Yan X, Chi Z, Si L, et al · · 2019 · cited 137× · PMID 31403867 · DOI 10.1200/jco.19.00210
2. Immunotherapy in Acral and Mucosal Melanoma: Current Status and Future Directions.
   Mao L, Qi Z, Zhang L, Guo J, et al · · 2021 · cited 119× · PMID 34149718 · DOI 10.3389/fimmu.2021.680407
3. A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151).
   Si L, Zhang X, Shu Y, Pan H, et al · · 2019 · cited 107× · PMID 30981094 · DOI 10.1016/j.tranon.2019.02.007
4. Immune checkpoint inhibitors in advanced or metastatic mucosal melanoma: a systematic review.
   Li J, Kan H, Zhao L, Sun Z, et al · · 2020 · cited 36× · PMID 32489431 · DOI 10.1177/1758835920922028
5. Immunomodulatory Precision: A Narrative Review Exploring the Critical Role of Immune Checkpoint Inhibitors in Cancer Treatment.
   Qiu J, Cheng Z, Jiang Z, Gan L, et al · · 2024 · cited 29× · PMID 38791528 · DOI 10.3390/ijms25105490
6. Association of NRAS Mutation With Clinical Outcomes of Anti-PD-1 Monotherapy in Advanced Melanoma: A Pooled Analysis of Four Asian Clinical Trials.
   Zhou L, Wang X, Chi Z, Sheng X, et al · · 2021 · cited 27× · PMID 34290710 · DOI 10.3389/fimmu.2021.691032
7. Pembrolizumab in Chinese patients with advanced melanoma: 3-year follow-up of the KEYNOTE-151 study.
   Si L, Zhang X, Shu Y, Pan H, et al · · 2022 · cited 22× · PMID 36304457 · DOI 10.3389/fimmu.2022.882471
8. Immune Checkpoint Inhibitors in Advanced Acral Melanoma: A Systematic Review.
   Zheng Q, Li J, Zhang H, Wang Y, et al · · 2020 · cited 21× · PMID 33344255 · DOI 10.3389/fonc.2020.602705