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NCT02589522

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

Active, enrolled Phase 1 Results posted Last updated 8 October 2025
What this trial tests

Phase 1 trial testing Berzosertib in Metastatic Lung Neuroendocrine Neoplasm in 15 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
22 May 2017
Primary endpoint
23 August 2021
18 September 2026

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment15
Start date22 May 2017
Primary completion23 August 2021
Estimated completion18 September 2026
Sites9 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Metastatic Lung Neuroendocrine Neoplasm or Metastatic Lung Non-Small Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With a Dose-limiting Toxicity Primary · Up to 3 weeks after completing whole brain radiotherapy (WBRT)

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

GroupValue95% CI
Group 1 - Dose Level 12
Group 1 - Dose Level 20
Group 1 - Dose Level 17
Group 1 - Dose Level 22
Radiological Response Rate Secondary · 6 months

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.

GroupValue95% CI
Group 1 - Dose Level 10
Group 1 - Dose Level 20
Group 1 - Dose Level 10
Group 1 - Dose Level 20
Group 1 - Dose Level 13
Group 1 - Dose Level 20
Group 1 - Dose Level 16
Group 1 - Dose Level 21
Overall Survival (OS) Secondary · 12 months

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.

GroupValue95% CI
Group 1 - Dose Level 12
Group 1 - Dose Level 20
Group 1 - Dose Level 16
Group 1 - Dose Level 20
Group 1 - Dose Level 10
Group 1 - Dose Level 22

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 2 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group 1 - Dose Level 1
Serious: 5/9 (56%)
Deaths: 7/9
Group 1 - Dose Level 2
Serious: 0/2 (0%)
Deaths: 0/2

Serious adverse events (7 terms)

ReactionSystemGroup 1 - Dose Level 1Group 1 - Dose Level 2
AnemiaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
ConfusionPsychiatric disorders
DehydrationMetabolism and nutrition disorders
Otitis externaInfections and infestations
Platelet count decreasedInvestigations
SepsisInfections and infestations
Other adverse events (31 terms — click to expand)

ReactionSystemGroup 1 - Dose Level 1Group 1 - Dose Level 2
FatigueGeneral disorders
NauseaGastrointestinal disorders
HeadacheNervous system disorders
AlopeciaSkin and subcutaneous tissue disorders
AnemiaBlood and lymphatic system disorders
DizzinessNervous system disorders
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
VomitingGastrointestinal disorders
AgitationPsychiatric disorders
Alkaline phosphatase increasedInvestigations
AnorexiaMetabolism and nutrition disorders
ChillsGeneral disorders
ConfusionPsychiatric disorders
DehydrationMetabolism and nutrition disorders
Dermatitis radiationInjury, poisoning and procedural complications
DysgeusiaNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
FallInjury, poisoning and procedural complications
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
HypersomniaNervous system disorders
HyponatremiaMetabolism and nutrition disorders
Infusion related reactionGeneral disorders
Memory impairmentNervous system disorders
Mucosal infectionInfections and infestations
ParesthesiaNervous system disorders
PhotosensitivitySkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Rash acneiformSkin and subcutaneous tissue disorders
Watering eyesEye disorders
White blood cell count decreasedInvestigations

Most-reported serious reactions: Anemia, Anorexia, Confusion, Dehydration, Otitis externa, Platelet count decreased, Sepsis.

Data from ClinicalTrials.gov NCT02589522 adverse events section.

Sponsor's own description

This phase I trial studies the side effects and best dose of berzosertib (M6620 \[VX-970\]) when given together with whole brain radiation therapy in treating patients with non-small cell lung cancer, small cell lung cancer, or neuroendocrine tumors that have spread from the original (primary) tumor to the brain (brain metastases). Berzosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving berzosertib together with radiation therapy may work better compared to standard of care treatment, including brain surgery and radiation therapy, in treating patients with non-small cell lung cancer, small cell lung cancer, or neuroendocrine tumors.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. ATR/CHK1 inhibitors and cancer therapy.
    Qiu Z, Oleinick NL, Zhang J. · · 2018 · cited 282× · PMID 29054375 · DOI 10.1016/j.radonc.2017.09.043
  2. Targeting the ATR-CHK1 Axis in Cancer Therapy.
    Rundle S, Bradbury A, Drew Y, Curtin NJ. · · 2017 · cited 173× · PMID 28448462 · DOI 10.3390/cancers9050041
  3. Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer.
    Petroni G, Cantley LC, Santambrogio L, Formenti SC, et al · · 2022 · cited 154× · PMID 34819622 · DOI 10.1038/s41571-021-00579-w
  4. Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation.
    Topatana W, Juengpanich S, Li S, Cao J, et al · · 2020 · cited 128× · PMID 32883316 · DOI 10.1186/s13045-020-00956-5
  5. Targeting the DNA Damage Response in OSCC with TP53 Mutations.
    Lindemann A, Takahashi H, Patel AA, Osman AA, et al · · 2018 · cited 117× · PMID 29489434 · DOI 10.1177/0022034518759068
  6. Ataxia telangiectasia and Rad3-related inhibitors and cancer therapy: where we stand.
    Mei L, Zhang J, He K, Zhang J. · · 2019 · cited 104× · PMID 31018854 · DOI 10.1186/s13045-019-0733-6
  7. Progress towards a clinically-successful ATR inhibitor for cancer therapy.
    Barnieh FM, Loadman PM, Falconer RA. · · 2021 · cited 97× · PMID 34909652 · DOI 10.1016/j.crphar.2021.100017
  8. Targeting DNA damage repair in small cell lung cancer and the biomarker landscape.
    Sen T, Gay CM, Byers LA. · · 2018 · cited 95× · PMID 29535912 · DOI 10.21037/tlcr.2018.02.03

Verify or expand the search:

Other trials of Berzosertib

Trials testing the same drug.

Other recruiting trials for Metastatic Lung Neuroendocrine Neoplasm

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02589522.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing