Innocuité, pharmacocinétique et efficacité du MK-1308 en association avec le pembrolizumab (MK-3475) dans le traitement de tumeurs solides au stade avancé (MK-1308-001)

Titre officiel

Étude ouverte de phase I/II multicentrique à multiples groupes évaluant le MK-1308 en association avec le pembrolizumab chez des sujets atteints de tumeurs solides au stade avancé

Sommaire:

Cette étude évaluera l’innocuité, la tolérabilité, la pharmacocinétique (PK) et l’efficacité préliminaire de doses croissantes de MK-1308 lorsqu’il est utilisé en association avec le pembrolizumab chez des participants atteints de tumeurs solides à un stade avancé.

Description de l'essai

Primary Outcome:

  • Number of participants with a Dose Limiting Toxicity (DLT)
  • Number of participants with ≥1 adverse event (AE)
  • Number of participants discontinuing study treatment due to an AE
  • Coformulation Phase: Number of participants with ≥1 AE
  • Coformulation Phase: Number of participants discontinuing study treatment due to an AE
  • Efficacy Expansion: Number of participants with ≥1 AE
  • Efficacy Expansion: Number of participants discontinuing study treatment due to an AE
  • Efficacy Expansion: Objective Response Rate (ORR) as assessed by blinded independent central review (BICR) based on modified Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1
  • Coformulation Phase: Number of participants with ≥1 DLT
  • Coformulation Phase: Objective Response Rate (ORR) as assessed by blinded independent central review (BICR) based on modified Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
Secondary Outcome:
  • Dose Escalation: Area under the plasma concentration time curve (AUC) of quavonlimab
  • Dose Escalation: Minimum concentration (Cmin) of quavonlimab
  • Dose Escalation: Maximum concentration (Cmax) of quavonlimab
  • Dose Escalation: Area under the plasma concentration time curve (AUC) of pembrolizumab
  • Dose Escalation: Minimum concentration (Cmin) of pembrolizumab
  • Dose Escalation: Maximum concentration (Cmax) of pembrolizumab
  • Dose Escalation: Quavonlimab anti-drug antibody levels
  • Dose Escalation: Pembrolizumab anti-drug antibody levels
  • Dose Confirmation: Area under the plasma concentration time curve (AUC) of quavonlimab
  • Dose Confirmation: Minimum concentration (Cmin) of quavonlimab
  • Dose Confirmation: Maximum concentration (Cmax) of quavonlimab
  • Dose Confirmation: Area under the plasma concentration time curve (AUC) of pembrolizumab
  • Dose Confirmation: Minimum concentration (Cmin) of pembrolizumab
  • Dose Confirmation: Maximum concentration (Cmax) of pembrolizumab
  • Dose Confirmation: Quavonlimab anti-drug antibody levels
  • Dose Confirmation: Pembrolizumab anti-drug antibody levels
  • Efficacy Expansion: Area under the plasma concentration time curve (AUC) of quavonlimab
  • Efficacy Expansion: Minimum concentration (Cmin) of quavonlimab
  • Efficacy Expansion: Maximum concentration (Cmax) of quavonlimab
  • Efficacy Expansion: Area under the plasma concentration time curve (AUC) of pembrolizumab
  • Efficacy Expansion: Minimum concentration (Cmin) of pembrolizumab
  • Efficacy Expansion: Maximum concentration (Cmax) of pembrolizumab
  • Efficacy Expansion: Quavonlimab anti-drug antibody levels
  • Efficacy Expansion: Pembrolizumab anti-drug antibody levels
  • Coformulation Phase: Area under the plasma concentration time curve (AUC) of quavonlimab
  • Coformulation Phase: Minimum concentration (Cmin) of quavonlimab
  • Coformulation Phase: Maximum concentration (Cmax) of quavonlimab
  • Coformulation Phase: Area under the plasma concentration time curve (AUC) of pembrolizumab
  • Coformulation Phase: Minimum concentration (Cmin) of pembrolizumab
  • Coformulation Phase: Maximum concentration (Cmax) of pembrolizumab
  • Coformulation Phase: Quavonlimab anti-drug antibody levels
  • Coformulation Phase: Pembrolizumab anti-drug antibody levels
  • Japanese Cohort: Area under the plasma concentration time curve (AUC) of quavonlimab
  • Japanese Cohort: Minimum concentration (Cmin) of quavonlimab
  • Japanese Cohort: Maximum concentration (Cmax) of quavonlimab
  • Japanese Cohort: Area under the plasma concentration time curve (AUC) of pembrolizumab
  • Japanese Cohort: Minimum concentration (Cmin) of pembrolizumab
  • Japanese Cohort: Maximum concentration (Cmax) of pembrolizumab
  • Japanese Cohort: Quavonlimab anti-drug antibody levels
  • Japanese Cohort: Pembrolizumab anti-drug antibody levels
  • Chinese Cohort: Area under the plasma concentration time curve (AUC) of quavonlimab
  • Chinese Cohort: Minimum concentration (Cmin) of quavonlimab
  • Chinese Cohort: Maximum concentration (Cmax) of quavonlimab
  • Chinese Cohort: Area under the plasma concentration time curve (AUC) of pembrolizumab
  • Chinese Cohort: Minimum concentration (Cmin) of pembrolizumab
  • Chinese Cohort: Maximum concentration (Cmax) of pembrolizumab
  • Chinese Cohort: Quavonlimab anti-drug antibody levels
  • Chinese Cohort: Pembrolizumab anti-drug antibody levels
  • Dose Escalation: Objective Response Rate (ORR) as assessed by investigator based on modified RECIST Version 1.1
  • Dose Confirmation: Objective Response Rate (ORR) as assessed by investigator based on modified RECIST Version 1.1
  • Coformulation: Objective Response Rate (ORR) as assessed by investigator based on modified RECIST Version 1.1
  • Efficacy Expansion: Duration of Response (DOR) as assessed by BICR based on modified RECIST Version 1.1
  • Coformulation: Duration of Response (DOR) as assessed by BICR based on modified RECIST Version 1.1
After screening, participants are assigned to either the Dose Escalation Phase or Dose Confirmation Phase. The Dose Escalation Phase consists of 3 cohorts and will evaluate available PK and safety data from the first 6 participants of each cohort, including dose limiting toxicities (DLTs). The purpose of the Dose Confirmation Phase is to gather additional safety, tolerability, PK, and preliminary efficacy data of quavonlimab in combination with pembrolizumab. The 5 arms of the Dose Confirmation Phase will include advanced/metastatic non-small cell lung cancer (NSCLC) and second line advanced/metastatic small cell lung cancer (SCLC). In participants who have initial evidence of radiological progressive disease (PD) by modified Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, it will be at the discretion of the investigator whether to continue a participant on study treatment until repeat imaging is obtained. Protocol Amendment 4 will enroll participants with melanoma in an Efficacy Expansion Cohort. During the Efficacy Expansion Phase, participants will be randomized to receive either quavonlimab in combination with pembrolizumab or quavonlimab monotherapy. Protocol Amendment 7 will enroll participants in a new cohort (Arm I). During the Coformulation Phase, the safety and PK of a coformulated product of pembrolizumab/quavonlimab (MK-1308A) will be evaluated in comparison to that of the single, co-administered products given at the same dose and schedule. Protocol Amendment 8 will enroll participants in 3 new cohorts (Arms J, K, and L). Arm J enrolls participants with refractory melanoma and Arm K enrolls participants in mainland China with relapsed or refractory solid tumour. Arms J and K will receive pembrolizumab/quavonlimab. Arm L enrolls participants in Japan with first-line advanced NSCLC. Participants in Arm L will be divided into 4 sub-cohorts and these sub-cohorts will receive 4 cycles of an indicated chemotherapy PLUS pembrolizumab/quavonlimab.

Voir cet essai sur ClinicalTrials.gov

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