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Advanced Solid TumorPhase 1NCT02157792

M6620 First in Human Study

A Phase 1 study testing M6620, Gemcitabine and Cisplatin in people with Advanced Solid Tumor, run by EMD Serono Research & Development Institute, Inc. at 31 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics (PK) of M6620 in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor
What is being tested?
M6620, Gemcitabine and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
31 sitesin 2 countries
Study dates
10 Dec 2012to 11 Mar 2020
Phase
Phase 1
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Disease status
  • Parts A and B/B2: Histologically or cytologically confirmed advanced solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or for whom regimens containing gemcitabine, cisplatin, etoposide, and/or irinotecan might be considered, and with measurable disease according to RECIST criteria
  • Part C1:
  • For Pre-screening:
  • Advanced (metastatic or locally-advanced unresectable and not eligible for definitive treatment, e.g., surgery/radiotherapy), histologically confirmed non-small cell lung cancer (NSCLC)
  • Available historical tumor specimen at the time of pre-screening or willing to provide a tumor biopsy (core) if the biopsy may be considered as part of standard clinical practice for the participant
Show all 20Show fewer
  • Received or did not tolerate standard approved targeted therapy, if appropriate for tumor genotype
  • For Screening:
  • Measurable disease according to RECIST criteria
  • -Part C2:
  • Advanced (locally-advanced incurable or metastatic) histologically confirmed estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) negative breast cancer.
  • Adequate available historical tumor specimen or willing to provide a tumor biopsy (core) if the biopsy may be considered as part of standard clinical practice for the participant
  • Measurable disease according to RECIST criteria
  • -Part C3:
  • Advanced (locally-advanced incurable or metastatic) histologically confirmed SCLC that is platinum-resistant, defined as disease progression during initial treatment with a platinum-based regimen or progression within 90 days of completion of platinum therapy. Participants with platinum-resistant disease may receive a second-line non-platinum-based chemotherapy and subsequently be enrolled to this study. Participants who received and are resistant to a second-line platinum-based chemotherapy may also be enrolled into the study.
  • Adequate available historical tumor specimen or willing to provide a tumor biopsy (core) if the biopsy may be considered as part of standard clinical practice for the participant
  • Measurable disease according to RECIST criteria
  • WHO performance status of 0 or 1
  • Life expectancy of >=12 week
  • Hematological and biochemical indices within protocol specified ranges at screening.

Who cannot join

  • Radiotherapy (except for palliative reasons) endocrine therapy, immunotherapy, or chemotherapy during the previous 4 weeks (6 weeks for nitrosoureas and Mitomycin-C, and 4 weeks for investigational medicinal products) or less than 4 drug half-lives, whichever greater, before first dose of study drug.
  • Parts A, B and B2:
  • Greater than 6 cycles of prior treatment with cisplatin and/or carboplatin.
  • Part A/B: History of prior dose reductions or dose interruptions while receiving cisplatin or carboplatin due to toxicity from the platinum or intolerance to either agent.
  • Part B2: Prior exposure to irinotecan is permitted except for participants with a known hypersensitivity reaction to irinotecan.
  • Participants with a known history of Grade 4 thrombocytopenia or Grade 4 neutropenia while receiving prior therapy.
Show all 34Show fewer
  • Part C1:
  • Any cytotoxic chemotherapy beyond 1 line of platinum-based chemotherapy. One additional line of non-platinum based therapy in the advanced setting
  • Pre-screening Only*: Participants may currently be receiving platinum-based chemotherapy in the advanced setting, or have completed 1 line of platinum-based chemotherapy and are currently receiving a second-line non-platinum-based therapy or maintenance therapy
  • There is no restriction on prior immunotherapy or targeted therapy unless combined together with a cytotoxic agent
  • Any prior gemcitabine for the treatment of NSCLC in any setting within 6 months
  • Participants who are known to be TP53 wild-type, unless they are determined to have ATM loss of expression during screening or pre-screening or until all the planned participants with TP53 mutation are enrolled as determined by the medical monitor
  • Participants with unknown TP53 mutational status will be enrolled until the group of approximately 10 participants without TP53 mutation or until all the planned participants with TP53 mutation are enrolled as determined by the medical monitor
  • Part C2:
  • Any prior platinum therapy in the adjuvant or neoadjuvant within 6 months of screening
  • Relapse within 3 months of completion of prior adjuvant or neoadjuvant chemotherapy
  • Any prior chemotherapy in the metastatic setting with the exception of either a taxane or an anthracycline in the first-line metastatic setting
  • There is no restriction on prior immunotherapy or targeted therapy in the metastatic setting unless combined together with a cytotoxic agent
  • Participants with known BRCA1/BRCA2 germline mutations, either determined and documented prior to Screening, or determined during Screening. Participants with unknown BRCA1/BRCA2 status may be enrolled at discretion of the sponsor
  • Participants who are documented to be non-basaloid subtype using molecular profiling assay (e.g. PAM50 assay) prior to Screening
  • Participants with unknown BRCA1/BRCA2 or basaloid subtype status will be enrolled until the number of enrolled participant is approximately 40. If approximately 40 participants have been enrolled and a minimum of 30 participants who are basaloid positive and BRCA1/BRCA2 germline wild-type have not been enrolled, the basaloid subtype and BRCA status assay will be required at Screening to exclude participants who are basaloid negative or have BRCA1/BRCA2 germline mutations.
  • Part C3:
  • Prior platinum-sensitive participants , unless they progress on or within 90 days of completion of platinum-based regimen
  • There is no restriction on prior immunotherapy or targeted therapy in the metastatic setting unless combined together with a cytotoxic agent
  • During prior carboplatin therapy, requirement for dose reduction below AUC 5 mg.min/mL or discontinuation of carboplatin for toxicity or lack of tolerability.
  • Unresolved toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater from previous anti-cancer therapy or radiotherapy
  • History of spinal cord compression or brain metastases, unless asymptomatic, treated, stable, and not requiring treatment with steroids for at least 4 weeks before first dose of study drug. Any history of leptomeningeal metastases.
  • Female participants who are already pregnant or lactating, or plan to become pregnant within 6 months of the last dose of study drug are excluded. Female participants of childbearing potential must adhere to contraception guidelines
  • Male participants with partners of child-bearing potential must agree to adhere to contraception guidelines. Men with pregnant or lactating partners or partners who plan to become pregnant during the study or within 6 months of the last dose of study drug are excluded
  • Serious cardiac or other co-morbid disease, as specified in the protocol
  • Prior bone marrow transplant or extensive radiotherapy to greater than 15% of bone marrow
  • Part C:
  • Current malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin
  • Major surgery =<2 weeks before starting study drug, or incomplete recovery from a prior major surgical procedure.

Trial locations and contacts

31 sites in 2 countries.

31 sites in 2 countries

United States24 sites

  • Emory University

    Atlanta, Georgia, 30322

  • US Oncology - Texas Oncology-Midtown - Austin Midtown

    Austin, Texas, 78705

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Northwestern Center for Clinical Research

    Chicago, Illinois, 60611

  • University Hospitals Case Medical Center - Case Comprehensive Cancer Center at

    Cleveland, Ohio, 44106

  • OSU - James Comprehensive Cancer Center - Division of Hematology

    Columbus, Ohio, 43210

  • Texas Oncology, P.A.

    Dallas, Texas, 75231

  • Rocky Mountain Cancer Centers, LLP

    Denver, Colorado, 80218

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • Greenville Health System

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center PARTNER

    Hackensack, New Jersey, 07601

  • University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics - Partner

    Houston, Texas, 77030

  • Long Island Jewish Medical Center - Monter Cancer Center

    Lake Success, New York, 11042

  • Breslin Cancer Center

    Lansing, Michigan, 48910

  • University Of Minnesota Hospital

    Minneapolis, Minnesota, 55455

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Virginia Oncology Associates - Hampton

    Norfolk, Virginia, 23502

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic - Rochester

    Rochester, Minnesota, 55905

  • Texas Oncology San Antonio Medical Cente

    San Antonio, Texas, 78240

  • Sharp Memorial Hospital

    San Diego, California, 92123

  • Washington University in St. Louis

    St Louis, Missouri, 63110

  • Study site

    Stanford, California

  • Northwest Cancer Specialists , P.C.

    Vancouver, Washington, 98684

Other trials in United States

United Kingdom7 sites

  • Beatson West of Scotland Cancer Centre - Dept of Medical Oncology

    Glasgow, Scotland

  • Guy's Hospital - PARENT

    London

  • Sarah Cannon Research Institute UK

    London

  • The Christie - Dept of Oncology

    Manchester

  • Freeman Hospital - PARENT

    Newcastle upon Tyne, England

  • Churchill Hospital - PARENT

    Oxford, England

  • Royal Marsden Hospital - Dept of Oncology

    Sutton, Surrey

Other trials in United Kingdom

About this study

Official title: An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970/M6620 in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors

An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics (PK) of M6620 in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors

Keywords
Solid Tumor, Advanced Solid Tumor, VX12-970-001, M6620, VX-970, Gemcitabine, Cisplatin, Etoposide, Carboplatin, Irinotecan

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02157792
Study groupRoleWhat they receive
Part AExperimentalThis part will be 3 + 3 dose escalation study of M6620 in combination with gemcitabine as well as gemcitabine and cisplatin in participants with advanced solid tumors.
Receives: Drug: M6620; Drug: Gemcitabine; Drug: Cisplatin
Part BExperimentalThis part will be 3 + 3 dose escalation study of M6620 in combination with cisplatin or cisplatin and etoposide in participants with advanced solid tumors.
Receives: Drug: M6620; Drug: Cisplatin; Drug: Etoposide
Part B2ExperimentalThis part will be 3 + 3 dose escalation study of M6620 in combination with irinotecan in participants with advanced solid tumors.
Receives: Drug: M6620; Drug: Irinotecan
Part C1ExperimentalThis will be the expansion part of the study in which participants with advanced non-small cell lung cancer (NSCLC) will be administered M6620 in combination with gemcitabine.
Receives: Drug: M6620; Drug: Gemcitabine
Part C2ExperimentalThis will be the expansion part of the study in which participants with advanced triple negative breast cancer (TNBC) will be administered M6620 in combination with cisplatin.
Receives: Drug: M6620; Drug: Cisplatin
Part C3ExperimentalThis will be the expansion part of the study in which participants with platinum-resistant advanced small cell lung cancer (SCLC) will be administered M6620 in combination with cisplatin or carboplatin.
Receives: Drug: M6620; Drug: Cisplatin; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Parts A, B, B2, C1, C2, C3: Safety parameters, including adverse event (AEs), clinical laboratory values (serum chemistry, hematology, and urinalysis), vital signs, and electrocardiogram (ECG) assessments

    Measured: Screening through Safety Follow-up (approximately 22 weeks)

  2. Parts C1, C2, C3: Overall Response Rate (ORR) for all participants in Part C1 (NSCLC), ORR for participants in Part C2 (TNBC) who are basaloid subtype and BRCA1/BRCA2 germline wild-type, ORR for all participants in Part C3 (SCLC)

    Measured: 1 year

Secondary outcomes (12)

  1. Part A: Maximum tolerated dose (MTD) of M6620 administered in combination with cisplatin and gemcitabine and in combination with gemcitabine

    Measured: 1 year

  2. Part A: Pharmacokinetic (PK) parameter estimates of M6620 in combination with cisplatin and gemcitabine and in combination with gemcitabine

    Measured: 1 year

  3. Part B, B2: Maximum tolerated dose (MTD) of M6620 in combination with cisplatin or cisplatin and etoposide or irinotecan

    Measured: 1 year

  4. Part B, B2: PK parameter estimates of M6620 in combination with cisplatin or cisplatin and etoposide or irinotecan

    Measured: 1 year

  5. Part B: PK parameter estimates of etoposide derived from plasma concentration-time data after coadministration with M6620 and in the absence of M6620

    Measured: 1 year

  6. Parts A, B, B2: Objective tumor response (OR) as evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1

    Measured: 1 year

  7. Part C2: Overall Response Rate in all participants in Part C2

    Measured: 1 year

  8. Parts C1, C2, C3: Progression Free Survival (PFS)

    Measured: 1 year

  9. Parts C1, C2, C3: Response Duration (RD)

    Measured: 1 year

  10. Parts C1, C2, C3: Overall Survival (OS)

    Measured: 1 year

  11. Parts C1, C2, C3: Clinical benefit (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) of 6 months or greater)

    Measured: 1 year

  12. Parts C1, C2, C3: PK parameter estimates of M6620 including maximum concentrations (Cmax), area under the curve (AUC), apparent volume at steady state (Vss), clearance (CL) and terminal elimination half-life (t1/2)

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2014 (estimated)
  2. Study start10 Dec 2012
  3. Primary completion11 Mar 2020
  4. Study completion11 Mar 2020

Resources

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02157792
Sponsor's protocol ID
MS201923_0001
Other IDs
VX12-970-001, 2012-003126-25
Status last verified
Mar 2020
First submitted
1 Jun 2014
Last updated
1 Apr 2020
Results posted
No

Publications

  • Middleton MR, Dean E, Evans TRJ, Shapiro GI, Pollard J, Hendriks BS, Falk M, Diaz-Padilla I, Plummer R. Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine +/- cisplatin in patients with advanced solid tumours. Br J Cancer. 2021 Aug;125(4):510-519. doi: 10.1038/s41416-021-01405-x. Epub 2021 May 26.

    PubMed 34040175

  • Shapiro GI, Wesolowski R, Devoe C, Lord S, Pollard J, Hendriks BS, Falk M, Diaz-Padilla I, Plummer R, Yap TA. Phase 1 study of the ATR inhibitor berzosertib in combination with cisplatin in patients with advanced solid tumours. Br J Cancer. 2021 Aug;125(4):520-527. doi: 10.1038/s41416-021-01406-w. Epub 2021 May 26.

    PubMed 34040174

  • Terranova N, Jansen M, Falk M, Hendriks BS. Population pharmacokinetics of ATR inhibitor berzosertib in phase I studies for different cancer types. Cancer Chemother Pharmacol. 2021 Feb;87(2):185-196. doi: 10.1007/s00280-020-04184-z. Epub 2020 Nov 4.

    PubMed 33145616

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing M6620, Gemcitabine and Cisplatin in people with Advanced Solid Tumor, run by EMD Serono Research & Development Institute, Inc. at 31 sites in 2 countries.

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 20 inclusion and 34 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 1 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Parts A, B, B2, C1, C2, C3: Safety parameters, including adverse event (AEs), clinical laboratory values (serum chemistry, hematology, and urinalysis), vital signs, and electrocardiogram (ECG) assessments (time frame: Screening through Safety Follow-up (approximately 22 weeks)). The study lists 2 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 NCT02157792, which also lists 3 linked publications.

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 1 Apr 2020.

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