Phase 1/1b Study of Oral PMD-026 in Patients With Metastatic Breast Cancer and Metastatic Triple Negative Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04115306|
Recruitment Status : Active, not recruiting
First Posted : October 4, 2019
Last Update Posted : September 27, 2022
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer Triple Negative Breast Cancer||Drug: PMD-026||Phase 1|
This study will evaluate the safety and tolerability of PMD-026 using an accelerated titration design to define the MTD in metastatic breast cancer, followed by an expansion at the RP2D in triple negative breast cancer. All patients will receive daily oral doses of PMD-026 until either disease progression or unacceptable toxicity. Patients will have disease assessments initially after 6 weeks of treatment, and every 9 weeks thereafter.
Patients enrolled to the Dose Escalation Phase must have histologically or cytologically diagnosed metastatic breast cancer that has progressed on or after standard of care therapy. Patients enrolled to the Dose Expansion Phase must have histologically or cytologically diagnosed metastatic triple negative breast cancer from initial diagnosis (ER/PgR <1%, HER2 negative) that has progressed on or after standard of care therapy. All patients must provide tumor tissue (archival preferred) prior to study entry.
A subset (N=12) of patients in Part 2 of the study will participate in a 1- week evaluation of the effect of food on PMD-026 oral absorption.
PMD-026 is an oral, reversible small molecule inhibitor of RSK1-4 with high selectivity for RSK2. High levels of RSK2 expression have been associated with worse overall survival in breast cancer. Inhibiting RSK2 may inhibit growth of breast cancer.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1/1b Multicenter, Open-Label, First-in-Human Dose Escalation and Dose Expansion Study to Assess Safety and Tolerability of Orally Administered PMD-026 in Patients With Metastatic Breast Cancer With Expansion in Metastatic Triple Negative Breast Cancer|
|Actual Study Start Date :||November 14, 2019|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||March 2024|
Oral PMD-026 (dose: 25 - 1000 mg), given daily until disease progression or unacceptable toxicity
Oral RSK1-4 inhibitor
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Through study completion, an average of 12 weeks ]Toxicities will be assessed in each patient by tracking the occurrence of graded Adverse Events (AEs). AEs will be graded according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v5.0.
- Maximum tolerated dose (MTD) of PMD-026 [ Time Frame: Up to 21 days ]The MTD will be defined as the dose level at which no more than one of six patients experiences a dose limiting toxicity (DLT) after 21 days of treatment have occurred, with the next higher dose having at least 2 of 3 or 2 of 6 patients experiencing a DLT.
- Recommended Phase 2 Dose (RP2D) of PMD-026 [ Time Frame: Up to 14 months ]The RP2D will be determined following the determination of the MTD and an overall assessment of safety as determined by the Safety Committee.
- Efficacy in Patients [ Time Frame: 6 weeks ]Anti-tumor activity (efficacy) will be assessed in all patients.
- Plasma Concentration [ Time Frame: 24 hours ]The plasma concentration will be measured as part of pharmacokinetic (PK) testing.
- Time to Response [ Time Frame: 6 weeks ]The time to response will be evaluated by disease assessments.
- Duration of Response [ Time Frame: 6 weeks ]The duration of response will be evaluated by disease assessments from time of first response (CR or PR) to time of disease progression.
- Effect of food on PMD-026 PK [ Time Frame: 24 hours ]The effect of food on plasma concentration will be measured as part of pharmacokinetic (PK) testing.
- RSK2 Expression [ Time Frame: 6 weeks ]RSK2 expression will be evaluated in breast cancer tissue through immunohistochemistry (IHC).
- PMD-026 Activity in Tissue [ Time Frame: 6 weeks ]PMD-026 activity will be evaluated in Lehmann subtypes in breast cancer tissue.
- RSK2 Expression and Response [ Time Frame: 12 weeks ]The relationship between RSK2 expression and response will be evaluated following RSK2 IHC and disease assessments.
- PMD-026 pharmacodynamics and RSK signaling [ Time Frame: 2 weeks ]PMD-026 pharmacodynamics will be evaluated on RSK signaling.
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): NCT04115306
|United States, Arizona|
|Banner MD Anderson Cancer Center|
|Gilbert, Arizona, United States, 85234|
|The University of Arizona Cancer Center|
|Tucson, Arizona, United States, 85724|
|United States, California|
|University of California, Los Angeles (UCLA)|
|Los Angeles, California, United States, 90095|
|University of California, San Diego (UCSD)|
|San Diego, California, United States, 92093|
|United States, Florida|
|Florida Cancer Specialists & Research Institute|
|Sarasota, Florida, United States, 34232|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, New York|
|New York, New York, United States, 10032|
|United States, Ohio|
|Ohio State University|
|Columbus, Ohio, United States, 43210|
|United States, Texas|
|South Texas Accelerated Research Therapeutics|
|San Antonio, Texas, United States, 78229|