Study of the Safety, Tolerability, Pharmacokinetics and Efficacy of Pembrolizumab (MK-3475) in Chinese Participants With Non-Small-Cell Lung Cancer (MK-3475-032/KEYNOTE-032)

NCT02835690 | Completed Phase 1 Results

• 3 other identifiers: 3475-032MK-3475-032KEYNOTE-032
• Study Type: interventional
• Target: 44
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and efficacy of three doses of pembrolizumab (MK-3475) in adult Chinese participants with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Cycle 1 is 28 days long; subsequent cycles are 21 days long.

Conditions

Non-Small-Cell Lung Cancer

Keywords

programmed cell death 1 (PD-1, PD1); programmed cell death ligand 1 (PD-L1, PDL1); programmed cell death ligand 2 (PD-L2, PDL2)

Outcome Measures

Primary Outcomes (9)

• Number of Participants Who Experienced an Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to be a causal relationship with this treatment. An AE could therefore be any unfavourable 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who experienced at least one AE was reported per protocol for the first course of treatment.

  Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017)

• Number of Participants Who Discontinued Study Drug Due to an AE

  An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to be a causal relationship with this treatment. An AE could therefore be any unfavourable 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who discontinued study treatment due to an AE was reported per protocol for the first course of treatment.

  Up to ~12 months (through Final Analysis database cut-off date of 19-Sept-2017)

• Single Dose PK: Area Under the Plasma Concentration Curve From 0-28 Days (AUC[0-28 Days]) of Pembrolizumab

  AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days during cycle 1 to estimate AUC(0-28 days) following single dose administration for the first course of treatment.

  Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days

• Single-Dose PK: Maximum Plasma Concentration (Cmax) of Pembrolizumab

  Cmax was defined as the maximum concentration of pembrolizumab observed in plasma following a single dose. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days during cycle 1 to estimate Cmax following single dose administration for the first course of treatment.

  Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days

• Single Dose PK: Time to Cmax (Tmax) of Pembrolizumab

  Tmax was defined as the time required post dosing to reach a maximum plasma concentration of pembrolizumab. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days at cycle 1 to estimate Tmax following single dose administration for the first course of treatment.

  Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days

• Single Dose PK: Apparent Terminal Half-Life (t1/2) of Pembrolizumab

  t½ was defined as the time required to divide the pembrolizumab plasma concentration by two after reaching pseudo-equilibrium, following a single dose of pembrolizumab. Blood samples were collected pre-dose and post-dose at multiple time points up to 28 days at cycle 1 to estimate t½ following single dose administration for the first course of treatment.

  Cycle 1 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [±0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 1= 28 days

• Multiple Dose PK: Trough Plasma Concentration (Ctrough) of Pembrolizumab

  Ctrough was defined as the minimum concentration that occurred immediately prior to the administration of pembrolizumab in Cycle 8. Blood samples were collected pre-dose at Cycle 8 to estimate Ctrough following multiple dose administrations of pembrolizumab for the first course of treatment.

  Cycle 8 Day 1: pre-dose [-1 to 0 hour]. (Cycle 1 = 28 days, Cycles 2-8 = 21 days).

• Multiple Dose PK: AUC(0-21 Days) of Pembrolizumab at Steady State

  AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time at steady state following multiple doses. Blood samples were collected pre-dose and post-dose at multiple time points up to 21 days during cycle 8 to assess AUC(0-21 days) at steady state for the first course of treatment.

  Cycle 8 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [up to 0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 8 up to 175 days (Cycle 1 = 28 days, Cycles 2-8 = 21 days).

• Multiple Dose PK: Cmax of Pembrolizumab at Steady State

  Cmax was defined as the maximum concentration of pembrolizumab observed in plasma at steady state following multiple doses. Blood samples were collected pre-dose and post-dose at multiple time points up to 21 days during cycle 8 to assess Cmax assessment at steady state for the first course of treatment.

  Cycle 8 Day 1: pre-dose [-1 to 0 hour] and post-dose at 0 [up to 0.5], 6 [up to 0.5], 24, 48, 168, 336, and 504 [±2 for 24 to 504] hours after completion of pembrolizumab infusion. Cycle 8 up to 175 days (Cycle 1 = 28 days, Cycles 2-8 = 21 days).

Secondary Outcomes (7)

• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Central Radiologists' Review

  Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017)

• ORR Per Immune-related RECIST (irRECIST) as Assessed by Central Radiologists' Review

  Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017)

• Duration of Response (DOR) Per RECIST 1.1 as Assessed by Central Radiologists' Review

  Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017)

• DOR Per irRECIST as Assessed by Central Radiologists' Review

  Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017)

• Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Central Radiologists' Review

  Up to ~13 months (through Final Analysis database cut-off date of 19-Sept-2017)

Study Arms (3)

Pembrolizumab 2 mg/kg

EXPERIMENTAL

Participants will receive pembrolizumab 2 mg/kg administered intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.

Biological: Pembrolizumab

Pembrolizumab 10 mg/kg

EXPERIMENTAL

Participants will receive pembrolizumab 10 mg/kg administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.

Biological: Pembrolizumab

Pembrolizumab 200 mg Fixed Dose

EXPERIMENTAL

Participants will receive pembrolizumab 200 mg fixed dose administered IV Q3W for up to 35 administrations. Cycle 1 is 28 days and subsequent cycles are 21 days. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475

Pembrolizumab 10 mg/kg; Pembrolizumab 2 mg/kg; Pembrolizumab 200 mg Fixed Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is of the Chinese race (i.e., Chinese descent born in China) and has a Chinese home address.
• Has a life expectancy of at least 3 months.
• Has histologically-/cytologically-confirmed, advanced unresectable NSCLC and has measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the site.
• Has failed established standard medical anti-cancer therapies or has been intolerant to such therapy, or in the opinion of the investigator have been considered ineligible for any form of standard therapy on medical grounds.
• Has a score of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status within 3 days prior to the first dose of study drug.
• Has adequate organ function.
• Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
• Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.

You may not qualify if:

• Has had chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study therapy pembrolizumab, or who has not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks earlier.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
• Is expected to require any other form of antineoplastic therapy while on study (including maintenance therapy with another agent for NSCLC).
• Has a medical condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication.
• Has a known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the participant has undergone potentially curative therapy with no evidence of that disease for 5 years.
• Has known central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Had prior treatment targeting PD-1: PD-L1 axis or cytotoxic T-lymphocyte-associated protein, or was previously randomized in any pembrolizumab study. Examples of such agents include (but are not limited to): Nivolumab (BMS-936558, MDX-1106 or ONO-4538); Pidilizumab (CT-011); AMP-224; BMS-936559 (MDX-1105); MPDL3280A (RG7446); and MEDI4736.
• Has an active infection requiring systematic therapy.
• Is positive for Human Immunodeficiency Virus.
• Has known active Hepatitis B or C.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Has received or will receive a live vaccine within 30 days prior to the first administration of study drug.
• Is at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Ma Y, Fang W, Zhang Y, Yang Y, Hong S, Zhao Y, Xie S, Ge J, Zhou H, Zhao H, Zhang L. KEYNOTE-032: A Randomized Phase I Study of Pembrolizumab in Chinese Patients with Advanced Non-Small Cell Lung Cancer. Oncologist. 2020 Aug;25(8):650-e1145. doi: 10.1634/theoncologist.2020-0067. Epub 2020 Mar 5.

  PMID: 32134163 RESULT

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2016
• First Posted: July 18, 2016
• Study Start: August 4, 2016
• Primary Completion: September 19, 2017
• Study Completion: December 31, 2021
• Last Updated: October 26, 2022
• Results First Posted: October 7, 2019

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share