M6620 First in Human Study

Advanced Solid Tumor Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02157792
• Other study ID #: MS201923_0001
• Secondary ID: VX12-970-0012012
• Status: Completed
• Phase: Phase 1
• Start date: December 10, 2012
• Est. completion date: March 11, 2020

Study information

• Verified date: March 2020
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: March 11, 2020
• Est. primary completion date: March 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• M6620

• Gemcitabine

• Cisplatin

• Etoposide

• Carboplatin

• Irinotecan

Locations

Country	Name	City	State
United Kingdom	Beatson West of Scotland Cancer Centre - Dept of Medical Oncology	Glasgow	Scotland
United Kingdom	Guy's Hospital - PARENT	London
United Kingdom	Sarah Cannon Research Institute UK	London
United Kingdom	The Christie - Dept of Oncology	Manchester
United Kingdom	Freeman Hospital - PARENT	Newcastle Upon Tyne	England
United Kingdom	Churchill Hospital - PARENT	Oxford	England
United Kingdom	Royal Marsden Hospital - Dept of Oncology	Sutton	Surrey
United States	Emory University	Atlanta	Georgia
United States	US Oncology - Texas Oncology-Midtown - Austin Midtown	Austin	Texas
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Northwestern Center for Clinical Research	Chicago	Illinois
United States	University Hospitals Case Medical Center - Case Comprehensive Cancer Center at	Cleveland	Ohio
United States	OSU - James Comprehensive Cancer Center - Division of Hematology	Columbus	Ohio
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Rocky Mountain Cancer Centers, LLP	Denver	Colorado
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Greenville Health System	Greenville	South Carolina
United States	Hackensack University Medical Center PARTNER	Hackensack	New Jersey
United States	University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics - Partner	Houston	Texas
United States	Long Island Jewish Medical Center - Monter Cancer Center	Lake Success	New York
United States	Breslin Cancer Center	Lansing	Michigan
United States	University Of Minnesota Hospital	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Virginia Oncology Associates - Hampton	Norfolk	Virginia
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Texas Oncology San Antonio Medical Cente	San Antonio	Texas
United States	Sharp Memorial Hospital	San Diego	California
United States	Northwest Cancer Specialists , P.C.	Vancouver	Washington

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

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