Trial Outcomes & Findings for Testing the Safety of M6620 (VX-970) When Given With Standard Whole Brain Radiation Therapy for the Treatment of Brain Metastases From Non-small Cell Lung Cancer, Small Cell Lung Cancer, or Neuroendocrine Tumors (NCT NCT02589522)

Last Updated: 2025-10-08

Results Overview

Defined as any grade 3 or more non-hematological toxicity requiring more than 5 day interruption in therapy or any grade 4 or higher hematological toxicity that is attributable to the berzosertib (M6620 \[VX-970\]) and/or whole brain radiotherapy

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1

Target enrollment

15 participants

Primary outcome timeframe

Up to 3 weeks after completing whole brain radiotherapy (WBRT)

Results posted on

2025-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	Group 1 - Dose Level 1 Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 50 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 1 - Dose Level 2 Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 100 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.
Overall Study STARTED	11	4
Overall Study COMPLETED	9	2
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1 - Dose Level 1 Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 50 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 1 - Dose Level 2 Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 100 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 2 Patients receive berzosertib at the identified dose in Group 1 by infusion over 60-90 minutes 2-4 hours prior to surgery. After surgery, patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib at the dose identified in Group 1 by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.
Overall Study Physician Decision	1	2	0
Overall Study Did not start treatment	1	0	0

Baseline Characteristics

Testing the Safety of M6620 (VX-970) When Given With Standard Whole Brain Radiation Therapy for the Treatment of Brain Metastases From Non-small Cell Lung Cancer, Small Cell Lung Cancer, or Neuroendocrine Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 - Dose Level 1 n=11 Participants Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 50 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 1 - Dose Level 2 n=4 Participants Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 100 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 2 Patients receive berzosertib at the identified dose in Group 1 by infusion over 60-90 minutes 2-4 hours prior to surgery. After surgery, patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib at the dose identified in Group 1 by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Total n=15 Participants Total of all reporting groups
Age, Continuous	59 years n=5 Participants	63 years n=7 Participants	—	59 years n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	1 Participants n=7 Participants	—	9 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	—	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	4 Participants n=7 Participants	—	15 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	—	2 Participants n=4 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	3 Participants n=7 Participants	—	13 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Region of Enrollment United States	11 participants n=5 Participants	4 participants n=7 Participants	—	15 participants n=4 Participants
Height	162.5 centimeter (cm) n=5 Participants	179.2 centimeter (cm) n=7 Participants	—	170 centimeter (cm) n=4 Participants
Weight	74.5 kilogram (kg) n=5 Participants	69.3 kilogram (kg) n=7 Participants	—	72.7 kilogram (kg) n=4 Participants
Body Surface Area	1.9 meters squared (m^2) n=5 Participants	1.9 meters squared (m^2) n=7 Participants	—	1.9 meters squared (m^2) n=4 Participants

PRIMARY outcome

Timeframe: Up to 3 weeks after completing whole brain radiotherapy (WBRT)

Outcome measures

Outcome measures
Measure	Group 1 - Dose Level 1 n=9 Participants Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 50 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 1 - Dose Level 2 n=2 Participants Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 100 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 2 Patients receive berzosertib at the identified dose in Group 1 by infusion over 60-90 minutes 2-4 hours prior to surgery. After surgery, patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib at the dose identified in Group 1 by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.
Number of Participants With a Dose-limiting Toxicity Experiencing a dose limiting toxicity	2 Participants	0 Participants	—
Number of Participants With a Dose-limiting Toxicity Not experiencing a dose limiting toxicity	7 Participants	2 Participants	—

SECONDARY outcome

Timeframe: Up to 6-months post-completion of WBRT

Population: Not collected

Assessed using Hopkins Verbal Learning Test-Revised. Incidence of events will be expressed as proportions with exact 95% confidence limits.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to up to 6 months post-completion of WBRT

Population: Not collected

Measured by the Functional Assessment of Cancer Therapy-Brain. Descriptive statistics of the actual change scores will also be provided. The median change score and quartiles will be reported. Where relevant the proportion of patients experiencing a clinically significant change in score will be reported with 95% confidence limits.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months

Population: Study was closed before enrolling to Group 2.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is \>=30% decrease in the sum of the target lesions; Disease Progression (PD) is \>= 20% increase in the smallest sum of the target lesions; Stable Disease (SD) is between PR and PD.

Outcome measures

Outcome measures
Measure	Group 1 - Dose Level 1 n=9 Participants Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 50 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 1 - Dose Level 2 n=2 Participants Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 100 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 2 Patients receive berzosertib at the identified dose in Group 1 by infusion over 60-90 minutes 2-4 hours prior to surgery. After surgery, patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib at the dose identified in Group 1 by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.
Radiological Response Rate Complete response	0 Participants	0 Participants	—
Radiological Response Rate Partial response	0 Participants	0 Participants	—
Radiological Response Rate Stable disease	3 Participants	0 Participants	—
Radiological Response Rate Disease progression or Death	6 Participants	1 Participants	—
Radiological Response Rate No assessment	0 Participants	1 Participants	—

SECONDARY outcome

Timeframe: 6 months

Population: Not collected.

Kaplan-Meier estimates of median icPFS will be calculated. Patients alive without intracranial progression at last follow-up will be censored at the date of the last radiologic assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Population: Study was closed before enrolling to Group 2.

Kaplan-Meier estimates of OS will be calculated. For calculation of OS, patients alive at last follow-up will be censored. Exploratory Cox regression analysis with M6620 (VX-970) dose as a covariate will be performed.

Outcome measures

Outcome measures
Measure	Group 1 - Dose Level 1 n=8 Participants Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 50 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 1 - Dose Level 2 n=2 Participants Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 100 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 2 Patients receive berzosertib at the identified dose in Group 1 by infusion over 60-90 minutes 2-4 hours prior to surgery. After surgery, patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib at the dose identified in Group 1 by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.
Overall Survival (OS) Alive	2 Participants	0 Participants	—
Overall Survival (OS) Deceased	6 Participants	0 Participants	—
Overall Survival (OS) Not evaluable	0 Participants	2 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 12 months

Population: Not collected

Descriptive statistics of the actual change scores will also be provided. The median change score and quartiles will be reported. Where relevant the proportion of patients experiencing a clinically significant change in score will be reported with 95% confidence limits.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: During surgery, pre-dose, and 2 hours and 50 minutes after start of M6620 (VX-970) infusion

Population: Not collected.

Pharmacokinetics of the presence of M6620 (VX-970) in blood, CSF, and tissue will be assessed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 3 weeks post completion of WBRT

Population: Not collected

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 months

Population: Not collected

Descriptive statistics of the actual change scores will be provided.

Outcome measures

Outcome data not reported

Adverse Events

Group 1 - Dose Level 1

Serious events: 5 serious events

Other events: 9 other events

Deaths: 7 deaths

Group 1 - Dose Level 2

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group 1 - Dose Level 1 n=9 participants at risk Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 50 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 1 - Dose Level 2 n=2 participants at risk Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 100 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.
Blood and lymphatic system disorders Anemia	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Metabolism and nutrition disorders Anorexia	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Psychiatric disorders Confusion	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Metabolism and nutrition disorders Dehydration	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Infections and infestations Otitis externa	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Investigations Platelet count decreased	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Infections and infestations Sepsis	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years

Other adverse events

Other adverse events
Measure	Group 1 - Dose Level 1 n=9 participants at risk Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 50 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.	Group 1 - Dose Level 2 n=2 participants at risk Patients undergo whole-brain radiation therapy Monday through Friday for 3 weeks for a total of 15 fractions. Patients also receive berzosertib 100 mg by infusion over 60-90 minutes twice a week, 18-30 hours after first radiation therapy.
Psychiatric disorders Agitation	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Investigations Alkaline phosphatase increased	11.1% 1/9 • Number of events 3 • Up to 2 years	0.00% 0/2 • Up to 2 years
Skin and subcutaneous tissue disorders Alopecia	22.2% 2/9 • Number of events 2 • Up to 2 years	0.00% 0/2 • Up to 2 years
Blood and lymphatic system disorders Anemia	22.2% 2/9 • Number of events 6 • Up to 2 years	0.00% 0/2 • Up to 2 years
Metabolism and nutrition disorders Anorexia	11.1% 1/9 • Number of events 2 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years
General disorders Chills	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Psychiatric disorders Confusion	11.1% 1/9 • Number of events 1 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Dehydration	11.1% 1/9 • Number of events 2 • Up to 2 years	0.00% 0/2 • Up to 2 years
Injury, poisoning and procedural complications Dermatitis radiation	11.1% 1/9 • Number of events 2 • Up to 2 years	0.00% 0/2 • Up to 2 years
Nervous system disorders Dizziness	22.2% 2/9 • Number of events 2 • Up to 2 years	0.00% 0/2 • Up to 2 years
Nervous system disorders Dysgeusia	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Epistaxis	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Injury, poisoning and procedural complications Fall	11.1% 1/9 • Number of events 2 • Up to 2 years	0.00% 0/2 • Up to 2 years
General disorders Fatigue	66.7% 6/9 • Number of events 8 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years
Musculoskeletal and connective tissue disorders Generalized muscle weakness	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Nervous system disorders Headache	33.3% 3/9 • Number of events 3 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years
Nervous system disorders Hypersomnia	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Metabolism and nutrition disorders Hyponatremia	0.00% 0/9 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years
General disorders Infusion related reaction	11.1% 1/9 • Number of events 1 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years
Investigations Lymphocyte count decreased	22.2% 2/9 • Number of events 3 • Up to 2 years	100.0% 2/2 • Number of events 2 • Up to 2 years
Nervous system disorders Memory impairment	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Infections and infestations Mucosal infection	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Gastrointestinal disorders Nausea	55.6% 5/9 • Number of events 6 • Up to 2 years	0.00% 0/2 • Up to 2 years
Nervous system disorders Paresthesia	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Skin and subcutaneous tissue disorders Photosensitivity	0.00% 0/9 • Up to 2 years	50.0% 1/2 • Number of events 1 • Up to 2 years
Investigations Platelet count decreased	22.2% 2/9 • Number of events 3 • Up to 2 years	0.00% 0/2 • Up to 2 years
Skin and subcutaneous tissue disorders Pruritus	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Skin and subcutaneous tissue disorders Rash acneiform	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Gastrointestinal disorders Vomiting	22.2% 2/9 • Number of events 4 • Up to 2 years	0.00% 0/2 • Up to 2 years
Eye disorders Watering eyes	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years
Investigations White blood cell count decreased	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/2 • Up to 2 years

Additional Information

Grants Administrative Manager

Johns Hopkins University

Phone: 4439273568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60