Trial Outcomes & Findings for A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer (NCT NCT05054374)
NCT ID: NCT05054374
Last Updated: 2025-05-23
Results Overview
DLT Evaluable Population consists of patients who receive at least 80% of planned total doses of mirdametinib in cycle 1 (in Arm 1 only, also both doses of fulvestrant) and are observed within 28 days following the first dose of mirdametinib or patients who experience a DLT.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
6 participants
Primary outcome timeframe
28 days from first day of treatment
Results posted on
2025-05-23
Participant Flow
All participants received Mirdametinib 4 mg BID PO and no participants were de-escalated to Mirdametinib 2 mg BID PO Continuous
Participant milestones
| Measure |
Arm 1, Part 1 - Mirdametinib in Combination With Fulvestrant
Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.
Part 1: safety run-in (confirmation of the RP2D for mirdametinib in combination with the standard recommended dose of fulvestrant). This part may include the mirdametinib dose de-escalation according to the 3+3 design if necessary
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
Fulvestrant: The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows:
* Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant
* (Only to be triggered pending DLTs on higher Dose Levels as described below)
* Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant
|
Arm 1, Part 2 - Mirdametinib in Combination With Fulvestrant
Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.
Part 2: dose expansion cohorts where the mirdametinib RP2D will be administered in combination with the standard recommended dose of fulvestrant
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
Fulvestrant: The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows:
* Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant
* (Only to be triggered pending DLTs on higher Dose Levels as described below)
* Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant
|
Arm 2, Part 1 - Mirdametinib as Single Agent
Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway
Part 1: mirdametinib dose escalation to MTD or RP2D according to the 3+3 design
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
|
Arm 2, Part 2 - Mirdametinib as Single Agent
Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway
Part 2: dose expansion cohorts
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
0
|
0
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Arm 1, Part 1 - Mirdametinib in Combination With Fulvestrant
Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.
Part 1: safety run-in (confirmation of the RP2D for mirdametinib in combination with the standard recommended dose of fulvestrant). This part may include the mirdametinib dose de-escalation according to the 3+3 design if necessary
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
Fulvestrant: The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows:
* Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant
* (Only to be triggered pending DLTs on higher Dose Levels as described below)
* Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant
|
Arm 1, Part 2 - Mirdametinib in Combination With Fulvestrant
Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.
Part 2: dose expansion cohorts where the mirdametinib RP2D will be administered in combination with the standard recommended dose of fulvestrant
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
Fulvestrant: The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows:
* Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant
* (Only to be triggered pending DLTs on higher Dose Levels as described below)
* Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant
|
Arm 2, Part 1 - Mirdametinib as Single Agent
Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway
Part 1: mirdametinib dose escalation to MTD or RP2D according to the 3+3 design
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
|
Arm 2, Part 2 - Mirdametinib as Single Agent
Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway
Part 2: dose expansion cohorts
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
Overall Study
Progressive Disease
|
5
|
0
|
0
|
0
|
Baseline Characteristics
A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer
Baseline characteristics by cohort
| Measure |
Arm 2, Part 1 - Mirdametinib as Single Agent
Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway
Part 1: mirdametinib dose escalation to MTD or RP2D according to the 3+3 design
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
|
Arm 2, Part 2 - Mirdametinib as Single Agent
Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway
Part 2: dose expansion cohorts
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
|
Arm 1, Part 1 - Mirdametinib in Combination With Fulvestrant
n=6 Participants
Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.
Part 1: safety run-in (confirmation of the RP2D for mirdametinib in combination with the standard recommended dose of fulvestrant). This part may include the mirdametinib dose de-escalation according to the 3+3 design if necessary
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
Fulvestrant: The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows:
* Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant
* (Only to be triggered pending DLTs on higher Dose Levels as described below)
* Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant
|
Arm 1, Part 2 - Mirdametinib in Combination With Fulvestrant
Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.
Part 2: dose expansion cohorts where the mirdametinib RP2D will be administered in combination with the standard recommended dose of fulvestrant
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
Fulvestrant: The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows:
* Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant
* (Only to be triggered pending DLTs on higher Dose Levels as described below)
* Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant
|
Total
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
—
|
—
|
54 years
n=5 Participants
|
—
|
54 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
—
|
—
|
6 Participants
n=5 Participants
|
—
|
6 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
—
|
—
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
—
|
—
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
—
|
—
|
4 Participants
n=5 Participants
|
—
|
4 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
—
|
—
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
—
|
—
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
—
|
—
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
—
|
—
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
—
|
—
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
—
|
—
|
6 Participants
n=5 Participants
|
—
|
6 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
—
|
—
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
—
|
—
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
—
|
—
|
6 Participants
n=5 Participants
|
—
|
6 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 28 days from first day of treatmentPopulation: N/A - Data were not collected
DLT Evaluable Population consists of patients who receive at least 80% of planned total doses of mirdametinib in cycle 1 (in Arm 1 only, also both doses of fulvestrant) and are observed within 28 days following the first dose of mirdametinib or patients who experience a DLT.
Outcome measures
Outcome data not reported
Adverse Events
Arm 1, Part 1 - Mirdametinib in Combination With Fulvestrant
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Arm 1, Part 2 - Mirdametinib in Combination With Fulvestrant
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Arm 2, Part 1 - Mirdametinib as Single Agent
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Arm 2, Part 2 - Mirdametinib as Single Agent
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm 1, Part 1 - Mirdametinib in Combination With Fulvestrant
n=6 participants at risk
Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.
Part 1: safety run-in (confirmation of the RP2D for mirdametinib in combination with the standard recommended dose of fulvestrant). This part may include the mirdametinib dose de-escalation according to the 3+3 design if necessary
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
Fulvestrant: The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows:
* Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant
* (Only to be triggered pending DLTs on higher Dose Levels as described below)
* Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant
|
Arm 1, Part 2 - Mirdametinib in Combination With Fulvestrant
Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway.
Part 2: dose expansion cohorts where the mirdametinib RP2D will be administered in combination with the standard recommended dose of fulvestrant
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
Fulvestrant: The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows:
* Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant
* (Only to be triggered pending DLTs on higher Dose Levels as described below)
* Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant
|
Arm 2, Part 1 - Mirdametinib as Single Agent
Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway
Part 1: mirdametinib dose escalation to MTD or RP2D according to the 3+3 design
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
|
Arm 2, Part 2 - Mirdametinib as Single Agent
Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway
Part 2: dose expansion cohorts
Mirdametinib: Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously
|
|---|---|---|---|---|
|
Investigations
Alkaline phosphatase increased
|
16.7%
1/6 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
|
Investigations
CPK increased
|
33.3%
2/6 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
|
Investigations
Lymphocyte count decreased
|
33.3%
2/6 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
—
0/0 • Up to 1 year
Participants only enrolled to Arm 1
|
Additional Information
Dr. Ezra Rosen, MD, PhD
Memorial Sloan Kettering Cancer Center
Phone: 646-888-6955
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place