Trial Outcomes & Findings for Milademetan in Advanced/Metastatic Solid Tumors (NCT NCT05012397)
NCT ID: NCT05012397
Last Updated: 2024-10-17
Results Overview
Overall Response Rate (ORR) of treatment with milademetan, as defined as the percentage of patients who have achieved confirmed complete response (CR) or Partial Response (PR) according to RECIST v1.1
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
40 participants
Primary outcome timeframe
From first dose date to first confirmed complete or partial response or study completion date; up to 23.5 months.
Results posted on
2024-10-17
Participant Flow
All enrolled participants (40 participants) received the study medication. Twenty-eight (28) discontinued treatment. Fourteen (14) completed the study.
Participant milestones
| Measure |
Milademetan (RAIN-32)
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
Overall Study
STARTED
|
40
|
|
Overall Study
COMPLETED
|
14
|
|
Overall Study
NOT COMPLETED
|
26
|
Reasons for withdrawal
| Measure |
Milademetan (RAIN-32)
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
Overall Study
Death
|
10
|
|
Overall Study
Physician Decision
|
9
|
|
Overall Study
Withdrawal by Subject
|
5
|
|
Overall Study
Lost to Follow-up
|
2
|
Baseline Characteristics
Milademetan in Advanced/Metastatic Solid Tumors
Baseline characteristics by cohort
| Measure |
Milademetan (RAIN-32)
n=40 Participants
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
Age, Continuous
|
56.5 years
STANDARD_DEVIATION 13.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
32 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
40 participants
n=5 Participants
|
|
BMI
|
24.8 kg/m2
STANDARD_DEVIATION 5.1 • n=5 Participants
|
PRIMARY outcome
Timeframe: From first dose date to first confirmed complete or partial response or study completion date; up to 23.5 months.Population: This analysis is conducted in all participants within the Centrally confirmed population (CCP) which is defined as all participants who had at least one dose of study treatment and also have WT TP53 and MDM2 amplification with CN ≥ 8 by central testing.
Overall Response Rate (ORR) of treatment with milademetan, as defined as the percentage of patients who have achieved confirmed complete response (CR) or Partial Response (PR) according to RECIST v1.1
Outcome measures
| Measure |
Milademetan (RAIN-32)
n=31 Participants
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
To Determine the ORR of Treatment With Milademetan in Patients With Advanced/Metastatic Solid Tumors With MDM2 Gene Amplification.
|
3.2 percentage of participants
Interval 0.1 to 16.7
|
SECONDARY outcome
Timeframe: From start date of response to first PD or study completion date; up to 23.5 monthsPopulation: This analysis is conducted in all participants within the Centrally confirmed population (CCP) who had a confirmed CR or PR.
DOR defined as the time from the date of first documentation of CR or PR according to RECIST v1.1 to the date of disease progression or death due to any cause according to Investigator assessment
Outcome measures
| Measure |
Milademetan (RAIN-32)
n=1 Participants
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
Duration of Response (DOR)
|
3.84 months
|
SECONDARY outcome
Timeframe: From the first dose date to the earliest date of recurrence, progression, death, or study completion; up to 23.5 monthsPopulation: The efficacy analysis is conducted in all participants within the Centrally confirmed population (CCP).
PFS defined as the time from the date of the first dose of the study drug to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause according to Investigator assessment
Outcome measures
| Measure |
Milademetan (RAIN-32)
n=31 Participants
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
Progression-free Survival (PFS)
|
3.5 months
Interval 1.8 to 3.7
|
SECONDARY outcome
Timeframe: From the start date of the most recent prior line of therapy to the PD date on the study; up to 23.5 monthsPopulation: The efficacy analysis is conducted in all participants within the Centrally confirmed population (CCP).
GMI defined as the ratio of Time to Progression (TTP) with the nth line of therapy (TTPn; here defined as milademetan) to the most recent prior line of therapy (TTPn-1)
Outcome measures
| Measure |
Milademetan (RAIN-32)
n=31 Participants
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
Growth Modulation Index (GMI)
|
0.76 months
Interval 0.47 to 0.98
|
SECONDARY outcome
Timeframe: From first dose date to first CR, PR, or stable disease (SD) >= 16 weeks, or study completion date; up to 23.5 monthsPopulation: The efficacy analysis is conducted in all participants within the Centrally confirmed population (CCP).
DCR defined as the percentage of patients with confirmed CR, PR, or stable disease (SD) for ≥ 16 weeks
Outcome measures
| Measure |
Milademetan (RAIN-32)
n=31 Participants
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
Disease Control Rate (DCR)
|
22.6 percentage of participants
Interval 9.6 to 41.1
|
Adverse Events
Milademetan (RAIN-32)
Serious events: 11 serious events
Other events: 40 other events
Deaths: 10 deaths
Serious adverse events
| Measure |
Milademetan (RAIN-32)
n=40 participants at risk
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Blood and lymphatic system disorders
Leukocytosis
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Blood and lymphatic system disorders
Normocytic anemia
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Nervous system disorders
Dizziness
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Nervous system disorders
Presyncope
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Nervous system disorders
Seizure
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Nervous system disorders
Syncope
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Gastrointestinal disorders
Ascites
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Ear and labyrinth disorders
Tympanic membrane perforation
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Investigations
blood creatine increased
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor Haemorrhage
|
2.5%
1/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
Other adverse events
| Measure |
Milademetan (RAIN-32)
n=40 participants at risk
260 mg once daily (QD) orally on Days 1 to 3 and Days 15 to 17 of each 28-day cycle
|
|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
52.5%
21/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Gastrointestinal disorders
vomiting
|
50.0%
20/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Gastrointestinal disorders
Nausea
|
45.0%
18/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
General disorders
Fatigue
|
40.0%
16/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Gastrointestinal disorders
Diarrhoea
|
32.5%
13/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Blood and lymphatic system disorders
Anemia
|
25.0%
10/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Blood and lymphatic system disorders
Neutropenia
|
22.5%
9/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
8/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Gastrointestinal disorders
Ascites
|
12.5%
5/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Nervous system disorders
Dizziness
|
12.5%
5/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
12.5%
5/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
4/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.0%
4/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Nervous system disorders
Headache
|
10.0%
4/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
10.0%
4/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
General disorders
Edema peripheral
|
10.0%
4/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.0%
4/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.0%
4/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
4/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Respiratory, thoracic and mediastinal disorders
COVID-19
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Gastrointestinal disorders
Constipation
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Gastrointestinal disorders
Dry mouth
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Infections and infestations
Influenza
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
General disorders
Pyrexia
|
7.5%
3/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Investigations
Blood Creatinine increased
|
5.0%
2/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Nervous system disorders
Dysgeusia
|
5.0%
2/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
General disorders
Face oedema
|
5.0%
2/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.0%
2/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
General disorders
Mucosal inflammation
|
5.0%
2/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.0%
2/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Nervous system disorders
Seizure
|
5.0%
2/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
|
Nervous system disorders
Taste disorder
|
5.0%
2/40 • From the first dose date to 30 days after the last dose date or study completion date whichever came first; up to 23.5 months
meets definition
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place