M6620 First in Human Study

NCT02157792 | Completed Phase 1

• 3 other identifiers: MS201923_0001VX12-970-0012012-003126-25
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 31

Brief 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

Conditions

Advanced Solid Tumor

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

  Screening through Safety Follow-up (approximately 22 weeks)

• 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)

  1 year

Secondary Outcomes (12)

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

  1 year

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

  1 year

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

  1 year

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

  1 year

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

  1 year

Study Arms (6)

Part A

EXPERIMENTAL

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.

Drug: M6620; Drug: Gemcitabine; Drug: Cisplatin

Part B

EXPERIMENTAL

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.

Drug: M6620; Drug: Cisplatin; Drug: Etoposide

Part B2

EXPERIMENTAL

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

Drug: M6620; Drug: Irinotecan

Part C1

EXPERIMENTAL

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.

Drug: M6620; Drug: Gemcitabine

Part C2

EXPERIMENTAL

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.

Drug: M6620; Drug: Cisplatin

Part C3

EXPERIMENTAL

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.

Drug: M6620; Drug: Cisplatin; Drug: Carboplatin

Interventions

M6620 DRUG

Also known as: VX-970

Part A; Part B; Part B2; Part C1; Part C2; Part C3

Gemcitabine DRUG

Part A; Part C1

Cisplatin DRUG

Part A; Part B; Part C2; Part C3

Etoposide DRUG

Part B

Carboplatin DRUG

Part C3

Irinotecan DRUG

Part B2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (31)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

Unknown Facility

Stanford, California, United States

Location

Rocky Mountain Cancer Centers, LLP

Denver, Colorado, 80218, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern Center for Clinical Research

Chicago, Illinois, 60611, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Breslin Cancer Center

Lansing, Michigan, 48910, United States

Location

University Of Minnesota Hospital

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center PARTNER

Hackensack, New Jersey, 07601, United States

Location

Long Island Jewish Medical Center - Monter Cancer Center

Lake Success, New York, 11042, United States

Location

University Hospitals Case Medical Center - Case Comprehensive Cancer Center at

Cleveland, Ohio, 44106, United States

Location

OSU - James Comprehensive Cancer Center - Division of Hematology

Columbus, Ohio, 43210, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

US Oncology - Texas Oncology-Midtown - Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology, P.A.

Dallas, Texas, 75231, United States

Location

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

Houston, Texas, 77030, United States

Location

Texas Oncology San Antonio Medical Cente

San Antonio, Texas, 78240, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates - Hampton

Norfolk, Virginia, 23502, United States

Location

Northwest Cancer Specialists , P.C.

Vancouver, Washington, 98684, United States

Location

Freeman Hospital - PARENT

Newcastle upon Tyne, England, United Kingdom

Location

Churchill Hospital - PARENT

Oxford, England, United Kingdom

Location

Beatson West of Scotland Cancer Centre - Dept of Medical Oncology

Glasgow, Scotland, United Kingdom

Location

Royal Marsden Hospital - Dept of Oncology

Sutton, Surrey, United Kingdom

Location

Guy's Hospital - PARENT

London, United Kingdom

Location

Sarah Cannon Research Institute UK

London, United Kingdom

Location

The Christie - Dept of Oncology

Manchester, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 34040175 DERIVED

• 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.

  PMID: 34040174 DERIVED

• 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.

  PMID: 33145616 DERIVED

MeSH Terms

Interventions

berzosertib; Gemcitabine; Cisplatin; Etoposide; Carboplatin; Irinotecan

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Camptothecin; Alkaloids

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2014
• First Posted: June 6, 2014
• Study Start: December 10, 2012
• Primary Completion: March 11, 2020
• Study Completion: March 11, 2020
• Last Updated: April 1, 2020

Record last verified: 2020-03

Locations

US (24); GB (7)