Trial Outcomes & Findings for M6620 (VX-970) in Selected Solid Tumors (NCT NCT03718091)
NCT ID: NCT03718091
Last Updated: 2023-07-07
Results Overview
Changes in the levels of Phospho-Chk1 in biopsy specimens of patients treated with M6620 monotherapy from baseline to cycle 1 day 15. This is a pharmacodynamic endpoint to evaluate target engagement. Results are in percent change of Phospho-Chk1 levels from baseline versus on-treatment biopsies.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
30 participants
Primary outcome timeframe
Baseline, Day 15
Results posted on
2023-07-07
Participant Flow
The original study was a planned molecular lead-in followed by a basket study (6 per cohort x4 cohorts; 24 total). 6 patients were replaced as they either did not receive study drug or were unable to complete paired biopsies (replacement permitted per protocol). Thus, Cohorts T1,T2, and T3 have \>6 pts. One patient slot was not accrued for T4. The basket study was not opened due to lack of efficacy in the lead-in.
Participant milestones
| Measure |
Cohort T1: ATRX-mutant Leiomyosarcoma
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T2: Truncating ATM Mutation
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T3: Other HR Gene Mutations and Replicative Stress
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T4: SDH-Mutant GIST
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
7
|
9
|
5
|
|
Overall Study
COMPLETED
|
8
|
7
|
9
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
M6620 (VX-970) in Selected Solid Tumors
Baseline characteristics by cohort
| Measure |
Cohort T1: ATRX-mutant Leiomyosarcoma
n=8 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T2: Truncating ATM Mutation
n=7 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T3: Other HR Gene Mutations and Replicative Stress
n=9 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T4: SDH-Mutant GIST
n=5 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 15Population: change in phospho-Chk1
Changes in the levels of Phospho-Chk1 in biopsy specimens of patients treated with M6620 monotherapy from baseline to cycle 1 day 15. This is a pharmacodynamic endpoint to evaluate target engagement. Results are in percent change of Phospho-Chk1 levels from baseline versus on-treatment biopsies.
Outcome measures
| Measure |
Cohort T1: ATRX-mutant Leiomyosarcoma
n=5 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T2: Truncating ATM Mutation
n=3 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T3: Other HR Gene Mutations
n=4 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T4: SDH-Mutant GIST
n=1 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
|---|---|---|---|---|
|
Changes in Phospho-Chk1 Levels in Biopsy Specimens
|
156 percent change
Interval -45.0 to 511.0
|
196 percent change
Interval 131.0 to 272.0
|
89 percent change
Interval -36.0 to 603.0
|
84 percent change
Interval 84.0 to 84.0
|
PRIMARY outcome
Timeframe: Baseline, Day 15Population: paired biopsies
Changes in the levels of yH2AX in biopsy specimens of patients treated with M6620 monotherapy from baseline to cycle 1 day 15.
Outcome measures
| Measure |
Cohort T1: ATRX-mutant Leiomyosarcoma
n=5 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T2: Truncating ATM Mutation
n=3 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T3: Other HR Gene Mutations
n=4 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T4: SDH-Mutant GIST
n=1 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
|---|---|---|---|---|
|
Change in yH2AX Levels in Biopsy Specimens
|
-36.8 percent change
Interval -83.9 to 820.4
|
142.2 percent change
Interval -40.5 to 395.9
|
-34.3 percent change
Interval -50.9 to 114.5
|
-30.8 percent change
Interval -30.8 to -30.8
|
PRIMARY outcome
Timeframe: 16 weeksThe number of participants that achieve either Stable Disease (SD), Partial Response (PR), or Complete Response (CR) at 16 weeks. * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Outcome measures
| Measure |
Cohort T1: ATRX-mutant Leiomyosarcoma
n=8 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T2: Truncating ATM Mutation
n=7 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T3: Other HR Gene Mutations
n=9 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T4: SDH-Mutant GIST
n=5 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
|---|---|---|---|---|
|
Disease Control Rate
|
0 absolute # pts with CR/PR/SD at 16 wks
|
0 absolute # pts with CR/PR/SD at 16 wks
|
0 absolute # pts with CR/PR/SD at 16 wks
|
2 absolute # pts with CR/PR/SD at 16 wks
|
SECONDARY outcome
Timeframe: AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE.Adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE 5.0)
Outcome measures
| Measure |
Cohort T1: ATRX-mutant Leiomyosarcoma
n=29 Participants
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T2: Truncating ATM Mutation
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T3: Other HR Gene Mutations
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
Cohort T4: SDH-Mutant GIST
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
|---|---|---|---|---|
|
Number of Participants With Treatment Related Serious Adverse Events
|
12 Participants
|
—
|
—
|
—
|
Adverse Events
Cohorts T1-4
Serious events: 12 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Cohorts T1-4
n=29 participants at risk
M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle.
M6620: M6620 is a drug designed to inhibit the ATR enzyme. Inhibiting ATR may block how cancers repair their naturally damaged DNA, handle cancer cell stress, and maintain cancer cell life and health.
|
|---|---|
|
Hepatobiliary disorders
grade 4 elevated AST
|
3.4%
1/29 • Number of events 1 • AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE. The study length for collection of AEs was 575 days total.
An AE is any untoward medical occurrence in a patient or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE analyzed together in this heterogeneous population.
|
|
Hepatobiliary disorders
grade 3 AST increase
|
6.9%
2/29 • Number of events 2 • AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE. The study length for collection of AEs was 575 days total.
An AE is any untoward medical occurrence in a patient or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE analyzed together in this heterogeneous population.
|
|
Hepatobiliary disorders
grade 2 alkaline phosphatase increase
|
6.9%
2/29 • Number of events 2 • AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE. The study length for collection of AEs was 575 days total.
An AE is any untoward medical occurrence in a patient or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE analyzed together in this heterogeneous population.
|
|
Hepatobiliary disorders
elevated bilirubin
|
3.4%
1/29 • Number of events 1 • AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE. The study length for collection of AEs was 575 days total.
An AE is any untoward medical occurrence in a patient or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE analyzed together in this heterogeneous population.
|
|
Blood and lymphatic system disorders
grade 3 anemia
|
3.4%
1/29 • Number of events 1 • AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE. The study length for collection of AEs was 575 days total.
An AE is any untoward medical occurrence in a patient or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE analyzed together in this heterogeneous population.
|
|
Immune system disorders
grade 3 anaphylaxis
|
3.4%
1/29 • Number of events 1 • AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE. The study length for collection of AEs was 575 days total.
An AE is any untoward medical occurrence in a patient or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE analyzed together in this heterogeneous population.
|
|
Blood and lymphatic system disorders
grade 3 febrile neutropenia
|
3.4%
1/29 • Number of events 1 • AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE. The study length for collection of AEs was 575 days total.
An AE is any untoward medical occurrence in a patient or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE analyzed together in this heterogeneous population.
|
|
Hepatobiliary disorders
grade 3 ALT increase
|
10.3%
3/29 • Number of events 3 • AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE. The study length for collection of AEs was 575 days total.
An AE is any untoward medical occurrence in a patient or clinical study subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AE analyzed together in this heterogeneous population.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place