Pevonedistat and Pembrolizumab for the Treatment of dMMR/MSI-H Metastatic or Locally Advanced Unresectable Solid Tumor
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|ClinicalTrials.gov Identifier: NCT04800627|
Recruitment Status : Active, not recruiting
First Posted : March 16, 2021
Last Update Posted : January 21, 2022
|Condition or disease||Intervention/treatment||Phase|
|Locally Advanced Malignant Solid Neoplasm Metastatic Malignant Solid Neoplasm Unresectable Malignant Solid Neoplasm||Biological: Pembrolizumab Drug: Pevonedistat||Phase 1 Phase 2|
I. Determine safety and phase II dose of pevonedistat in combination with pembrolizumab. (Phase I) II. To assess the efficacy of pevonedistat in combination with pembrolizumab in patients with dMMR/MSI-H cancers.
I. To assess additional efficacy endpoints of the combination of pevonedistat and pembrolizumab in dMMR/MSI-H cancers.
II. To assess the safety of pevonedistat and pembrolizumab in the dMMR/MSI-H patient cohort.
III. To assess the pharmacodynamics impact of pevonedistat and pembrolizumab on tumor and immune-related components.
I. Immune context evaluation of tumor microenvironment. II. Determine clinical benefit. III. Evaluate pevonedistat pharmacokinetics and resistance mechanisms in combination therapy.
OUTLINE: This is a phase I, dose escalation study of pevonedistat followed by a phase II study.
Patients receive pevonedistat intravenously (IV) over 60 minutes on days 1, 3, and 5, and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Pevonedistat in Combination With Pembrolizumab in Patients With dMMR/MSI-H Cancers|
|Actual Study Start Date :||March 29, 2021|
|Estimated Primary Completion Date :||October 17, 2022|
|Estimated Study Completion Date :||October 17, 2022|
Experimental: Treatment (pevonedistat, pembrolizumab)
Patients receive pevonedistat IV over 60 minutes on days 1, 3, and 5, and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- Recommended phase 2 dose of pevonedistat when combined with pembrolizumab (Phase I) [ Time Frame: 21 days ]
- Objective response (partial response [PR] or complete response [CR]) (Phase II) [ Time Frame: Through study completion, an average of 1 year ]Will be assessed by immune modified Response Evaluation Criteria in Solid Tumors (iRECIST) version (v) 1.1.
- Changes in protein misfolding [ Time Frame: Up to 24 weeks ]Will analyze the pharmacodynamics impact of pevonedistat by evaluating changes in protein misfolding between pre-treatment and on-treatment tumor biopsies.
- Progression free survival (PFS) [ Time Frame: Through study completion, an average of 1 year ]Will be assessed by iRECIST v1.1. Will be estimated using the method of Kaplan and Meier.
- Duration of response [ Time Frame: Through study completion, an average of 1 year ]
- Overall survival [ Time Frame: Through study completion, an average of 1 year ]Will be estimated using the method of Kaplan and Meier.
- Incidence of adverse events [ Time Frame: Through study completion, an average of 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04800627
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Michael J Overman||M.D. Anderson Cancer Center|