M6620 First in Human Study

NCT ID: NCT02157792

Last Updated: 2020-04-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-10

Study Completion Date

2020-03-11

Brief Summary

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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

Detailed Description

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Conditions

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Advanced Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A

This 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.

Group Type EXPERIMENTAL

M6620

Intervention Type DRUG

Gemcitabine

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

Part B

This part will be 3 + 3 dose escalation study of M6620 in combination with cisplatin or cisplatin and etoposide in participants with advanced solid tumors.

Group Type EXPERIMENTAL

M6620

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Part B2

This part will be 3 + 3 dose escalation study of M6620 in combination with irinotecan in participants with advanced solid tumors.

Group Type EXPERIMENTAL

M6620

Intervention Type DRUG

Irinotecan

Intervention Type DRUG

Part C1

This 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.

Group Type EXPERIMENTAL

M6620

Intervention Type DRUG

Gemcitabine

Intervention Type DRUG

Part C2

This 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.

Group Type EXPERIMENTAL

M6620

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

Part C3

This 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.

Group Type EXPERIMENTAL

M6620

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Interventions

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M6620

Intervention Type DRUG

Gemcitabine

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

Etoposide

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Irinotecan

Intervention Type DRUG

Other Intervention Names

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VX-970

Eligibility Criteria

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Inclusion Criteria

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
* 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.

Exclusion Criteria

* 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.

1. 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.
2. 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.
* Part C1:

* Any cytotoxic chemotherapy beyond 1 line of platinum-based chemotherapy. One additional line of non-platinum based therapy in the advanced setting

1. 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
2. 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

(a) 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Research & Development Institute, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany

Locations

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Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status

Sharp Memorial Hospital

San Diego, California, United States

Site Status

Stanford, California, United States

Site Status

Rocky Mountain Cancer Centers, LLP

Denver, Colorado, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern Center for Clinical Research

Chicago, Illinois, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Breslin Cancer Center

Lansing, Michigan, United States

Site Status

University Of Minnesota Hospital

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Washington University in St. Louis

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center PARTNER

Hackensack, New Jersey, United States

Site Status

Long Island Jewish Medical Center - Monter Cancer Center

Lake Success, New York, United States

Site Status

University Hospitals Case Medical Center - Case Comprehensive Cancer Center at

Cleveland, Ohio, United States

Site Status

OSU - James Comprehensive Cancer Center - Division of Hematology

Columbus, Ohio, United States

Site Status

Greenville Health System

Greenville, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

US Oncology - Texas Oncology-Midtown - Austin Midtown

Austin, Texas, United States

Site Status

Texas Oncology, P.A.

Dallas, Texas, United States

Site Status

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

Houston, Texas, United States

Site Status

Texas Oncology San Antonio Medical Cente

San Antonio, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Virginia Oncology Associates - Hampton

Norfolk, Virginia, United States

Site Status

Northwest Cancer Specialists , P.C.

Vancouver, Washington, United States

Site Status

Freeman Hospital - PARENT

Newcastle upon Tyne, England, United Kingdom

Site Status

Churchill Hospital - PARENT

Oxford, England, United Kingdom

Site Status

Beatson West of Scotland Cancer Centre - Dept of Medical Oncology

Glasgow, Scotland, United Kingdom

Site Status

Royal Marsden Hospital - Dept of Oncology

Sutton, Surrey, United Kingdom

Site Status

Guy's Hospital - PARENT

London, , United Kingdom

Site Status

Sarah Cannon Research Institute UK

London, , United Kingdom

Site Status

The Christie - Dept of Oncology

Manchester, , United Kingdom

Site Status

Countries

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United States United Kingdom

References

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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.

Reference Type DERIVED
PMID: 34040175 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34040174 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33145616 (View on PubMed)

Other Identifiers

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VX12-970-001

Identifier Type: OTHER

Identifier Source: secondary_id

2012-003126-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS201923_0001

Identifier Type: -

Identifier Source: org_study_id

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