Clinical Trials /

M6620 First in Human Study

NCT02157792

Description:

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

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: M6620 First in Human 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

Clinical Trial IDs

  • ORG STUDY ID: MS201923_0001
  • SECONDARY ID: VX12-970-001
  • SECONDARY ID: 2012-003126-25
  • NCT ID: NCT02157792

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
M6620VX-970Part A
GemcitabinePart A
CisplatinPart A
EtoposidePart B
CarboplatinPart C3
IrinotecanPart B2

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
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.
  • M6620
  • Gemcitabine
  • 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.
  • M6620
  • Cisplatin
  • Etoposide
Part B2ExperimentalThis part will be 3 + 3 dose escalation study of M6620 in combination with irinotecan in participants with advanced solid tumors.
  • M6620
  • 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.
  • M6620
  • 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.
  • M6620
  • 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.
  • M6620
  • Cisplatin
  • Carboplatin

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part A: Maximum tolerated dose (MTD) of M6620 administered in combination with cisplatin and gemcitabine and in combination with gemcitabine
Time Frame:1 year
Safety Issue:
Description:
Measure:Part A: Pharmacokinetic (PK) parameter estimates of M6620 in combination with cisplatin and gemcitabine and in combination with gemcitabine
Time Frame:1 year
Safety Issue:
Description:
Measure:Part B, B2: Maximum tolerated dose (MTD) of M6620 in combination with cisplatin or cisplatin and etoposide or irinotecan
Time Frame:1 year
Safety Issue:
Description:
Measure:Part B, B2: PK parameter estimates of M6620 in combination with cisplatin or cisplatin and etoposide or irinotecan
Time Frame:1 year
Safety Issue:
Description:
Measure:Part B: PK parameter estimates of etoposide derived from plasma concentration-time data after coadministration with M6620 and in the absence of M6620
Time Frame:1 year
Safety Issue:
Description:
Measure:Parts A, B, B2: Objective tumor response (OR) as evaluated by Response Criteria Evaluation in Solid Tumors (RECIST) 1.1
Time Frame:1 year
Safety Issue:
Description:
Measure:Part C2: Overall Response Rate in all participants in Part C2
Time Frame:1 year
Safety Issue:
Description:
Measure:Parts C1, C2, C3: Progression Free Survival (PFS)
Time Frame:1 year
Safety Issue:
Description:
Measure:Parts C1, C2, C3: Response Duration (RD)
Time Frame:1 year
Safety Issue:
Description:
Measure:Parts C1, C2, C3: Overall Survival (OS)
Time Frame:1 year
Safety Issue:
Description:
Measure:Parts C1, C2, C3: Clinical benefit (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) of 6 months or greater)
Time Frame:1 year
Safety Issue:
Description:
Measure: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)
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

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

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