Study of E7046 in Subjects With Selected Advanced Malignancies

NCT02540291 | Terminated Phase 1 Results

• 2 other identifiers: E7046-G000-1012014-004823-37
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 3

Brief Summary

This is an open label, multicenter, Phase 1 study of E7046 to assess the safety and tolerability of E7046 and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of E7046.

Conditions

Tumors

Keywords

E7046; Advanced malignancies; malignancies

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 2 years)

• Maximum Tolerated Dose (MTD) of E7046

  Cycle 1 (21 days)

• Recommended Phase 2 Dose (RP2D) of E7046

  Two RP2Ds were planned to be evaluated.

  Cycle 1 (21 days)

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  From first dose date until disease progression/recurrence (approximately up to 2 years)

• Progression-free Survival (PFS)

  From first dose date to the date of the first documentation of confirmed disease progression or death (approximately up to 2 years)

• Duration of Response (DOR)

  From the date of first documented confirmed irCR/irPR until the first documentation of confirmed disease progression or death (approximately up to 2 years)

• Disease Control Rate (DCR)

  From the first dose date until disease progression/recurrence (approximately up to 2 years)

• Clinical Benefit Rate (CBR)

  From first dose date until disease progression/recurrence (approximately up to 2 years)

Study Arms (1)

E7046

EXPERIMENTAL

Participants with tumor types that harbor high levels of myeloid infiltrate based on the Cancer Genome Atlas (TCGA).

Drug: E7046

Interventions

E7046 DRUG

E7046 will be administered as a single agent orally once daily (QD) continuously in 21-day cycles. In the dose escalation part, increasing doses of E7046 ranging from 125 mg to 750 mg will be administered to cohorts of 6 participants. In the cohort expansion part, participants will be treated at the RP2D.

E7046

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy greater than or equal to 12 weeks
• Participants must have any of the following tumor types, confirmed by available pathology records or current biopsy, that is advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists: pancreatic adenocarcinoma, renal clear cell carcinoma, SCCHN (squamous cell carcinoma of head and neck), NSCLC (non-small cell lung cancer), colorectal cancer (CRC), hepatocellular carcinoma (HCC), ovarian serous epithelial cancer, bladder transitional cancer, cervical cancer, and triple-negative breast cancer
• Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) must have been completed at least 4 weeks before study drug administration, and all adverse events (AEs) have either returned to baseline or stabilized
• Prior definitive radiation therapy must have been completed at least 6 weeks before study drug administration and the irradiated lesions should show evidence of progression if they are intended to be considered target lesions. Prior palliative radiotherapy must be completed at least 2 weeks before study drug administration. The radiotherapy-related side effects must have resolved before the study entry. No radiopharmaceuticals (strontium, samarium) will be allowed within 8 weeks before study drug administration.
• Participants must have accessible tumors and consent to repeated biopsy for performance of correlative tissue studies
• Must have at least one measurable lesion per irRECIST (immune-related Response Evaluation Criteria Criteria in Solid Tumors):
• At least 1 lesion of greater than or equal to 10 mm in the longest diameter for a non-lymph node or greater than or equal to 15 mm in the short-axis diameter for a lymph node that is serially measurable according to irRECIST using computerized tomography/magnetic resonance imaging (CT/MRI)
• Lesions that have had definitive external beam radiotherapy or locoregional therapies such as radiofrequency (RF) ablation or brachytherapy must show evidence of progressive disease to be deemed a target lesion
• Prior treated brain or meningeal metastases must be without evidence of progression (confirmed by MRI) for at least 8 weeks and off immunosuppressive doses of systemic steroids (greater than 10 mg/day prednisone or equivalent) for at least 4 weeks before study drug administration
• Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses greater than 7.5 to 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration.
• Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or multiple gated acquisition (MUGA) scan
• Adequate renal function defined as serum creatinine less than 1.5 X ULN (upper limit of normal) or use SI units or calculated creatinine clearance greater than or equal to 50 mL/min per the Cockcroft and Gault formula
• Adequate bone marrow function:

You may not qualify if:

• Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast that has completed curative therapy
• Participants with any active autoimmune disease (Appendix 2) or a documented history of autoimmune disease, poorly controlled asthma or history of syndrome that required systemic steroids or immunosuppressive medications, except for participants with vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.
• Participants with inflammatory bowel disease
• Known human immunodeficiency virus (HIV) infection
• Active infection requiring therapy, including known positive tests for Hepatitis B surface antigen and hepatitis C virus (HCV) RNA
• Major surgery within 4 weeks before the first dose of study drug
• Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids except inhaled or intranasal corticosteroids (with minimal systemic absorption)
• Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of E7046
• Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the participant's participation in this study
• Use of other investigational drugs within 28 days or at least 5 half-lives (whichever is shorter) before study drug administration
• Prior exposure to drugs that are antagonists of colony stimulating factor-1 receptor (CSF1R) like but not limited to emactuzumab (RG7155) (Roche), PLX3397 (Plexicon), and JNJ40346627 (J \& J)
• Use of any live vaccines (eg, intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) within 28 days
• Prolongation of corrected QT \[QTcF (Fridericia's corrected QT interval)\] interval to greater than 480 msec when electrolytes balance is normal
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment (including oral anticoagulation)
• Females who are pregnant (positive urine test) or breastfeeding

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (3)

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Villejuif, Cedex, France

Location

Related Publications (1)

• Hong DS, Parikh A, Shapiro GI, Varga A, Naing A, Meric-Bernstam F, Ataman O, Reyderman L, Binder TA, Ren M, Liu M, Dayal S, Siu AY, Sachdev P, Xu L, Bhagawati-Prasad V, Tchakov I, Ooi CE, Bao X, Marabelle A. First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE2-receptor E-type 4 (EP4), in patients with advanced cancers. J Immunother Cancer. 2020 Jun;8(1):e000222. doi: 10.1136/jitc-2019-000222.

  PMID: 32554609 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

E7046

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 3, 2015
• Study Start: July 30, 2015
• Primary Completion: February 27, 2018
• Study Completion: February 27, 2018
• Last Updated: February 17, 2020
• Results First Posted: February 17, 2020

Record last verified: 2018-07

Locations

US (2); FR (1)