Solid TumorPhase 2NCT03718091
M6620 (VX-970) in Selected Solid Tumors
A Phase 2 study testing M6620 in people with Solid Tumor and Leiomyosarcoma, run by Massachusetts General Hospital at 4 sites in United States.
Trial summary
This research study is studying a drug called M6620 as a possible treatment for advanced solid tumor. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Solid Tumor, Leiomyosarcoma, Osteosarcoma
- What is being tested?
- M6620
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- 8 Jan 2019to 8 Jul 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants Enrolling to the Translational Lead-in Study:
- For enrollment to cohort T1: participants must have metastatic or progressive LMS with a) treatment with at least one prior systemic therapy b) ATRX mutation by NGS
- For enrollment to cohorts T2 or T3: participants must have a histologically or cytologically confirmed advanced solid tumor for which no standard curative therapy is available.
- For enrollment to cohort T2: participants must have a truncating ATM mutation. Testing may be completed via the DFCI/BWH OncoPanel, MGH SNaPshot, or any other CLIA-certified method.
- For enrollment to cohort T3, participants must have one of the following (testing may be completed via the DFCI/BWH OncoPanel, MGH SNaPshot, or any CLIA-certified laboratory):
- Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
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- A somatic mutation in BRCA1 or BRCA2, or another mutation within a known HR gene including BARD1, BRIP1, CDK12, CHEK2, FANCA, FANCC, FANCE, FANCF, FANCM, MRE11A, NBN, PALB2, RAD51B, RAD51C, or RAD51D.
- A MYC amplification of greater than 6-fold.
- FBXW7 truncating or missense mutation designated as deleterious.
- CCNE1 amplification of greater than 8-fold.
- An ARID1A mutation as determined by the DFCI/BWH OncoPanel or any other CLIA-certified method.
- Other (unlisted) mutations within known HR genes may be considered with approval from the site principal investigator.
- For enrollment to cohort T4: participants must have GIST with known mutation in SDHX genes or loss of expression of SDHX protein(s), as determined by standard pathology assays. Prior therapy is not required.
- Age ≥ 18 years
- ECOG performance status ≤ 2 (Karnofsky [KPS] ≥ 60%; KPS of 50 is not permitted)
- Participants must have tumor amenable to biopsy, and be a candidate for tumor biopsy according to the treating investigator. The patient must be willing to undergo a fresh tumor biopsy for this study.
- Participants must have archival tissue available for analysis. Participants without available archival tissue enrolling to the translational lead-in study may instead use tissue from the fresh pre-treatment biopsy.
- Participants Enrolling to the Phase II:
- For enrollment to cohort 1A: participants must have metastatic or progressive osteosarcoma treated with at least one prior systemic therapy.
- For enrollment to cohort 1B: participants must have metastatic or progressive leiomyosarcoma treated with at least one prior systemic therapy.
- For enrollment to cohorts 2 - 5: participants must have a histologically or cytologically confirmed advanced solid tumor for which no standard curative therapy is available.
- For enrollment to cohort 2: participants must have a truncating ATM mutation. Testing may be completed via the DFCI/BWH OncoPanel, MGH SNaPshot, or any other CLIA-certified method.
- For enrollment to cohort 3A: participants must have a germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). Testing may be completed via the DFCI/BWH OncoPanel, MGH SNaPshot, or any CLIA-certified laboratory.
- For enrollment to cohort 3B: participants must have a somatic mutation in BRCA1 or BRCA2, or another mutation within a known HR gene including BARD1, BRIP1, CDK12, CHEK2, FANCA, FANCC, FANCE, FANCF, FANCM, MRE11A, NBN, PALB2, RAD51B, RAD51C, or RAD51D. Other (unlisted) mutations within known HR genes may be considered with approval from the site principal investigator.
- For enrollment to cohort 4A: participants must have a MYC amplification of greater than 6-fold or an FBXW7 truncating or missense mutation designated as deleterious, as determined by the DFCI/BWH OncoPanel, MGH SNaPshot, or any other CLIA-certified method.
- For enrollment to cohort 4B: participants must have a CCNE1 amplification of greater than 8-fold as determined by the DFCI/BWH OncoPanel, MGH SNaPshot, or any other CLIA-certified method.
- For enrollment to cohort 5: participants must have an ARID1A mutation as determined by the DFCI/BWH OncoPanel, MGH SNaPshot, or any other CLIA-certified method.
- For enrollment to cohort 1A: Age > 12
- For enrollment to cohorts 1B - 5: Age ≥ 18
- ECOG performance status ≤ 2 (Karnofsky ≥ 60%; KPS of 50 is not permitted) for participants ≥ 16 years of age, Lansky ≥ 50% for participants < 16 years of age
- Participants must have archival tissue available for analysis
- All Participants:
- If any participant could enroll to more than one cohort based on mutational status, the cohort enrollment decision will be discussed with the overall principal investigator. For example, if a participant has both an ATM mutation and an FBXW7 mutation and thus could enroll to either Cohort 2 or Cohort 4A, the decision of which cohort to enroll to will be made in conjunction with the overall principal investigator. The decision as to which cohort the participant should be enrolled on must be made prior to the initiation of study treatment.
- Participants must have RECIST 1.1 measurable disease.
- Participants must have normal organ and marrow function as defined below:
- All Participants:
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) for age
- Adult Participants (Age ≥ 18 years):
- AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN; OR
- 5 × institutional ULN if liver metastases are present
- Serum or plasma creatinine ≤ 1.5 × institutional ULN, OR
- Creatinine clearance ≥ 60 mL/min by Cockcroft-Gault equation for participants with creatinine levels above 1.5 × institutional ULN
- Pediatric Participants (Age < 18 years):
- ALT (SGPT) ≤ 3 × institutional (ULN)
- -for the purposes of this study, the ULN for SGPT will be defined as 45 U/L.
- Serum or plasma creatinine Participants 13 - 15 years: males ≤ 1.5 mg/dL, females
- ≤ 1.4 mg/dL, participants 16 - 17 years: males ≤ 1.7 mg/dL, females ≤ 1.4 mg/dL; OR
- Creatinine clearance ≥ 60 mL/min/1.73 m2 by Schwartz formula for participants with creatinine levels above the limits described above
- The effects of M6620 on the developing human fetus are unknown. For this reason and because anti-cancer agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of M6620 administration.
- Ability to understand and the willingness to sign a written informed consent document (or parent or legally authorized representative, if minor).
Who cannot join
- Participants who have had chemotherapy, immune therapy, other investigational therapy, major surgery, or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or participants who have not recovered to ≤ Grade 1 or baseline from therapies administered more than 3 weeks prior (with the exceptions of 1. Alopecia and peripheral neuropathies which may be ≤ Grade 2 at study entry and 2. Laboratory abnormalities that are not listed in 3.1 and that are not considered clinically meaningful [e.g. decreased lymphocyte count, electrolyte abnormalities]
- Participants who have received oral tyrosine kinase inhibitors (TKIs) within 5 half-lives of study entry.
- Participants who have previously received treatment with an ATR inhibitor, including but not limited to M6620 (VX-970).
- Participants with known untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with a history of brain metastases that have been treated, no longer require corticosteroids, and have been stable on imaging for at least one month following the end of treatment are permitted.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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- Pregnant women are excluded from this study because M6620 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620, breastfeeding should be discontinued if the mother is treated with M6620.
- Known HIV-positive participants are ineligible because of the increased risk of lethal infections when treated with potentially marrow-suppressive therapy.
- Patients with a history of another malignancy are excluded with the exception of 1. patients who remain disease-free for 3 years and 2. adequately treated cervical carcinoma in situ, non-melanoma skin cancer (e.g. basal cell, squamous cell carcinomas), low-risk thyroid cancer.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02214
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Boston Children Hospital
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: A Phase II Study of M6620 (VX-970) in Selected Solid Tumors
This research study is studying a drug called M6620 as a possible treatment for advanced solid tumor.
Read the detailed description
This study is made up of two phases: a Translational Lead-In Phase and a Phase II. These two phases serve different functions. The translational lead-in phase is designed to test the drug on a small number of patients in efforts to gain information on two research questions:
- If M6620 has an anti-cancer effect on participants
- If M6620 research findings that were discovered in laboratory studies are also found in human research studies.
Phase II is a much larger study to determine if M6620 has an anti-cancer effect in different groups of patients.
The FDA (the U.S. Food and Drug Administration) has not approved M6620 as a treatment for any disease.
ATR is an enzyme in cells that is responsible for multiple functions including repairing damaged DNA, helping cells that are stressed during the DNA copying process, and working to maintain the ends of chromosomes. In cancer cells, active ATR enzymes protect the cancer by helping the cells repair damage, stay alive, and maintain health. 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. Administration of M6620 may therefore assist in the slowing of growth or destruction of some cancers.
In this research study, the investigators are...
- Gathering initial data on the anti-cancer activity of M6620 when given alone to participants within selected cancer populations
- Determining if there are changes in the biological components in the participant's body that may be associated with damaged DNA repair
- Conditions
- Solid Tumor, Leiomyosarcoma, Osteosarcoma
- Being tested
- M6620
- Keywords
- Solid Tumor, leiomyosarcoma, Osteosarcoma
- Medical subject headings
- Leiomyosarcoma, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M6620Drug
Also called VX-970
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort T1: ATRX-mutant Leiomyosarcoma | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort T2: Truncating ATM Mutation | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort T3: Other HR Gene Mutations | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort 1A: Osteosarcoma | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort 1B: Leiomyosarcoma | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort 2: Truncating ATM mutation | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort 3A: Germline BRCA mutation | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort 3B: Other HR Alteration | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort 4A: MYC amplification, FBXW7 mutation | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort 4B: Cyclin E amplification | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort 5: ARID1A mutation | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
| Cohort T4: SDH-Mutant GIST | Experimental | M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. Receives: Drug: M6620 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Phospho-Chk1 Levels in Biopsy Specimens
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.
Measured: Baseline, Day 15
Change in yH2AX Levels in Biopsy Specimens
Changes in the levels of yH2AX in biopsy specimens of patients treated with M6620 monotherapy from baseline to cycle 1 day 15.
Measured: Baseline, Day 15
Disease Control Rate
The 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.
Measured: 16 weeks
Secondary outcomes (1)
Number of Participants With Treatment Related Serious Adverse Events
Adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE 5.0)
Measured: AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2018
- Study start8 Jan 2019
- Primary completion1 Jun 2020
- Study completion8 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- EMD Serono
- Responsible party
- Principal investigator, Gregory Cote, Massachusetts General Hospital
- Investigators
- Gregory M Cote, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03718091
- Sponsor's protocol ID
- 18-274
- Status last verified
- May 2023
- First submitted
- 19 Oct 2018
- Last updated
- 7 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
PubMed 31401903
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of M6620 (VX-970) in Selected Solid Tumors
- ClinicalTrials.gov ID
- NCT03718091
- Acronym / sponsor ID
- 18-274
- Conditions
- Solid Tumor, Leiomyosarcoma, Osteosarcoma
- Keywords
- Solid Tumor, leiomyosarcoma, Osteosarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- EMD Serono
- Study start
- 8 Jan 2019 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 8 Jul 2020 (actual)
- First posted
- 24 Oct 2018 (actual)
- Results
- Posted 7 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a drug called M6620 as a possible treatment for advanced solid tumor.
Detailed description
This study is made up of two phases: a Translational Lead-In Phase and a Phase II. These two phases serve different functions. The translational lead-in phase is designed to test the drug on a small number of patients in efforts to gain information on two research questions:
- If M6620 has an anti-cancer effect on participants
- If M6620 research findings that were discovered in laboratory studies are also found in human research studies.
Phase II is a much larger study to determine if M6620 has an anti-cancer effect in different groups of patients.
The FDA (the U.S. Food and Drug Administration) has not approved M6620 as a treatment for any disease.
ATR is an enzyme in cells that is responsible for multiple functions including repairing damaged DNA, helping cells that are stressed during the DNA copying process, and working to maintain the ends of chromosomes. In cancer cells, active ATR enzymes protect the cancer by helping the cells repair damage, stay alive, and maintain health. 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. Administration of M6620 may therefore assist in the slowing of growth or destruction of some cancers.
In this research study, the investigators are...
- Gathering initial data on the anti-cancer activity of M6620 when given alone to participants within selected cancer populations
- Determining if there are changes in the biological components in the participant's body that may be associated with damaged DNA repair
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Cohort T1: ATRX-mutant Leiomyosarcoma | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort T2: Truncating ATM Mutation | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort T3: Other HR Gene Mutations | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort 1A: Osteosarcoma | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort 1B: Leiomyosarcoma | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort 2: Truncating ATM mutation | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort 3A: Germline BRCA mutation | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort 3B: Other HR Alteration | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort 4A: MYC amplification, FBXW7 mutation | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort 4B: Cyclin E amplification | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort 5: ARID1A mutation | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
| Cohort T4: SDH-Mutant GIST | Experimental | Drug: M6620M6620 will administered intravenously on days 1,4, 8, 11, 15, 18, 22, 25 on a 28-day cycle. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (52 listed)
- For enrollment to cohort T1: participants must have metastatic or progressive LMS with a) treatment with at least one prior systemic therapy b) ATRX mutation by NGS
- For enrollment to cohorts T2 or T3: participants must have a histologically or cytologically confirmed advanced solid tumor for which no standard curative therapy is available.
- For enrollment to cohort T2: participants must have a truncating ATM mutation. Testing may be completed via the DFCI/BWH OncoPanel, MGH SNaPshot, or any other CLIA-certified method.
- For enrollment to cohort T3, participants must have one of the following (testing may be completed via the DFCI/BWH OncoPanel, MGH SNaPshot, or any CLIA-certified laboratory):
- For enrollment to cohort T4: participants must have GIST with known mutation in SDHX genes or loss of expression of SDHX protein(s), as determined by standard pathology assays. Prior therapy is not required.
Key exclusion criteria (9 listed)
- Participants who have had chemotherapy, immune therapy, other investigational therapy, major surgery, or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or participants who have not recovered to ≤ Grade 1 or baseline from therapies administered more than 3 weeks prior (with the exceptions of 1. Alopecia and peripheral neuropathies which may be ≤ Grade 2 at study entry and 2. Laboratory abnormalities that are not listed in 3.1 and that are not considered clinically meaningful [e.g. decreased lymphocyte count, electrolyte abnormalities]
- Participants who have received oral tyrosine kinase inhibitors (TKIs) within 5 half-lives of study entry.
- Participants who have previously received treatment with an ATR inhibitor, including but not limited to M6620 (VX-970).
- Participants with known untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Participants with a history of brain metastases that have been treated, no longer require corticosteroids, and have been stable on imaging for at least one month following the end of treatment are permitted.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| M6620Also: VX-970M6620 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. | Drug | Cohort 1A: Osteosarcoma, Cohort 1B: Leiomyosarcoma, Cohort 2: Truncating ATM mutation, Cohort 3A: Germline BRCA mutation, Cohort 3B: Other HR Alteration, Cohort 4A: MYC amplification, FBXW7 mutation, Cohort 4B: Cyclin E amplification, Cohort 5: ARID1A mutation, Cohort T1: ATRX-mutant Leiomyosarcoma, Cohort T2: Truncating ATM Mutation, Cohort T3: Other HR Gene Mutations, Cohort T4: SDH-Mutant GIST |
Primary outcome
Changes in Phospho-Chk1 Levels in Biopsy Specimens
Time frame: Baseline, Day 15
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.
Change in yH2AX Levels in Biopsy Specimens
Time frame: Baseline, Day 15
Changes in the levels of yH2AX in biopsy specimens of patients treated with M6620 monotherapy from baseline to cycle 1 day 15.
Disease Control Rate
Time frame: 16 weeks
The 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.
1 secondary outcome
Number of Participants With Treatment Related Serious Adverse Events
Time frame: AE data was collected from cycle 1 day 1 until 30 days after last dose or resolution of the AE.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31401903Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory M Cote, MD, PhD principal investigator
Massachusetts General Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing M6620 in people with Solid Tumor and Leiomyosarcoma, run by Massachusetts General Hospital at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 52 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Phospho-Chk1 Levels in Biopsy Specimens (time frame: Baseline, Day 15). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03718091, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2023.