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Tomivosertib (eFT-508) in Combination With PD-1/PD-L1 Inhibitor Therapy

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ClinicalTrials.gov Identifier: NCT03616834
Recruitment Status : Recruiting
First Posted : August 6, 2018
Last Update Posted : December 5, 2018
Sponsor:
Information provided by (Responsible Party):
Effector Therapeutics

Brief Summary:
Phase 2, open-label study that will evaluate the safety, tolerability, antitumor activities.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Tomivosertib (eFT-508) Phase 2

Detailed Description:
This Phase 2, open-label study will evaluate the safety, tolerability, antitumor activity, and pharmacokinetics (PK) of Tomivosertib (eFT-508) in subjects who have initiated anti-PD-1/anti-PD-L1 monotherapy and either developed progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 on therapy or have undergone 12 weeks of anti-PD-1/anti-PD-L1 therapy with no evidence of partial response (PR) or complete response (CR).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Subjects will continue their anti-PD-1/anti-PD-L1 therapy, which they had already initiated per standard of care according to the package insert, and then initiate Tomivosertib (eFT-508) at 200 mg twice daily (bid) 7 days prior to their next scheduled anti-PD-1/anti-PD-L1 therapy.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Tomivosertib (eFT-508) in Combination With PD-1/PD-L1 Inhibitor Therapy: A Study of Subjects Administered Anti-PD-1/Anti-PD-L1 Therapy That Are Experiencing Insufficient Response to Checkpoint Inhibitor Alone
Actual Study Start Date : July 25, 2018
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tomivosertib (eFT-508)
Tomivosertib (eFT-508) will be taken at 200 mg twice daily (bid). Subjects will continue their anti-PD-1/anti-PD-L1 therapy, which they had already initiated per standard of care according to the package insert.
Drug: Tomivosertib (eFT-508)
Tomivosertib (eFT-508) is a novel, small-molecule investigational drug being developed by eFFECTOR Therapeutics, as an antitumor therapy that acts by selectively inhibiting mitogen-activated protein kinase (MAPK)-interacting serine/threonine kinase (MNK)1 and MNK 2.
Other Name: MNK1 and MNK2




Primary Outcome Measures :
  1. Proportion of subjects with treatment-emergent AEs (TEAEs) and serious AEs (SAEs) [ Time Frame: 52 weeks ]
    The incidence of TEAEs and SAEs will be summarized and TEAEs will also be summarized by severity and according to their relationship to Tomivosertib (eFT-508).

  2. Overall Response Rate (ORR) as determined by RECIST 1.1 [ Time Frame: 52 weeks ]
    Defined as the proportion of subjects who achieve a best overall response of complete response (CR) or partial response (PR).

  3. Progression Free Survival (PFS) as determined by RECIST 1.1 [ Time Frame: 52 weeks ]
    Defined as the interval from the start of Tomivosertib (eFT-508) to the occurrence of PD or death from any cause.


Secondary Outcome Measures :
  1. ORR as determined by iRECIST [ Time Frame: 52 weeks ]
    Defined as the proportion of subjects who achieve a best overall response of CR assigned using iRECIST (iCR) or PR assigned using iRECIST (iPR).

  2. PFS as determined by iRECIST [ Time Frame: 52 weeks ]
    Defined as the interval from the start of Tomivosertib (eFT-508) to the occurrence of confirmed progression assigned using iRECIST (iCPD) or death from any cause.

  3. Overall survival [ Time Frame: 52 weeks ]
    Defined as time from the first dose date of Tomivosertib (eFT-508) to death due to any cause will be summarized.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must provide written informed consent and any authorizations required by local law;
  • Men or women 18 years of age;
  • Initiated monotherapy with an anti-PD-1 or anti-PD-L1 agent (avelumab, atezolizumab, durvalumab, nivolumab, or pembrolizumab) in accordance with the package insert, and:
  • Are judged by the Principal Investigator as tolerating the anti-PD-1 or anti-PD-L1 therapy, and
  • Developed PD per RECIST 1.1 on therapy, or
  • Have undergone 12 weeks of anti-PD-1 or anti-PD-L1 therapy with no evidence of PR or CR;
  • ECOG performance status of 0 or 1;
  • Has at least 1 measurable lesion per RECIST 1.1 criteria;
  • Adequate bone marrow function during Screening as defined below:
  • Absolute neutrophil count 1.0 109/L,
  • Platelet count 75 109/L, and
  • Hemoglobin 80 g/L (8.0 g/dL or 4.9 mmol/L);
  • Adequate hepatic function during Screening as defined below:
  • Serum alanine aminotransferase 3 upper limit of normal (ULN) or 5 ULN if liver metastases are present,
  • Serum aspartate aminotransferase 3 ULN or 5 ULN if liver metastases are present, and
  • Serum bilirubin - total 1.5 ULN (unless due to Gilbert's syndrome or hemolysis);
  • Adequate renal function during Screening, defined as measured or estimated creatinine clearance 60 mL/min calculated by the Cockcroft-Gault formula using actual body weight;
  • Adequate coagulation profile during Screening as defined below:
  • Prothrombin time within the ULN, and
  • Activated partial thromboplastin time within the ULN;
  • Negative antiviral serology during Screening as defined below:
  • Negative human immunodeficiency virus antibody,
  • Negative hepatitis B surface antigen and negative hepatitis B core antibody or undetectable hepatitis B virus (HBV) DNA by quantitative polymerase chain reaction (qPCR) testing. Note: Hepatocellular carcinoma (HCC) subjects with - -- HBV may only be enrolled if their hepatitis is judged clinically stable by the Investigator, and
  • Negative hepatitis C virus (HCV) antibody or negative HCV ribonucleic acid by q PCR. Note: HCC subjects with HCV are permitted provided they are not being actively treated;
  • Female subjects of childbearing potential must meet all of the following criteria:
  • Not pregnant (negative serum pregnancy test during Screening),
  • Not breastfeeding, and
  • Willing to use a protocol-recommended method of contraception or to abstain from heterosexual intercourse from the start of Tomivosertib (eFT-508) until at least 30 days after the last dose of Tomivosertib (eFT-508) or anti-PD-1/anti-PD-L1 therapy. Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone levels within the institutional laboratory postmenopausal range and a negative serum or urine beta human chorionic gonadotropin); or is menopausal (age 55 years with amenorrhea for 6 months);
  • Male subjects who can father a child must meet all of the following criteria:
  • Willing to use a protocol-recommended method of contraception or to abstain from heterosexual intercourse with females of childbearing potential from the start of Tomivosertib (eFT-508) until at least 30 days after the last dose of Tomivosertib (eFT-508) or anti-PD-1/anti-PD-L1 therapy, and
  • Willing to refrain from sperm donation from the start of Tomivosertib (eFT-508) until at least 90 days after the last dose of Tomivosertib (eFT-508) or anti-PD-1/anti-PD-L1 therapy. Note: A - male subject is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy;
  • Willing to comply with the scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered;
  • In the judgment of the Investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject's cancer; and
  • Estimated life expectancy of 3 months.

Exclusion Criteria:

  • Currently in CR or PR with anti-PD-1 or anti-PD-L1 monotherapy (avelumab, atezolizumab, durvalumab, nivolumab, or pembrolizumab);
  • History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical carcinoma; adequately treated, papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission; or any other cancer that has been in complete remission for 2 years
  • Gastrointestinal (GI) disease (eg, gastric or intestinal bypass surgery, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic diarrheal illness, bowel obstruction) that may interfere with drug absorption or with interpretation of GI AEs;
  • Known symptomatic brain metastases requiring 10 mg/day of prednisolone (or its equivalent). Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of Tomivosertib (eFT-508), fulfill the steroid requirement for these metastases, and are neurologically stable;
  • Significant cardiovascular disease, including myocardial infarction, arterial thromboembolism, or cerebrovascular thromboembolism, within 6 months prior to start of Tomivosertib (eFT-508); symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; Grade 3 hypertension (diastolic blood pressure 100 mmHg or systolic blood pressure 160 mmHg); or history of congenital prolonged QT syndrome;
  • Significant ECG abnormalities at Screening, including unstable cardiac arrhythmia requiring medication, left bundle branch block, second-degree atrioventricular (AV) block type II, third-degree AV block, Grade 2 bradycardia, or QT interval corrected using Fridericia's formula >450 msec (for men) or >470 msec (for women);
  • Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis;
  • Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the start of Tomivosertib (eFT-508). Note: Subjects with localized fungal infections of skin or nails are eligible. Subjects may be receiving prophylactic antibiotics as long as the antibiotic is not prohibited by the protocol due to the potential for drug-drug interactions;
  • Has received a live vaccine within 30 days of planned start of Tomivosertib (eFT-508);
  • Pregnant or breastfeeding;
  • Major surgery within 4 weeks before the start of Tomivosertib (eFT-508);
  • Prior solid organ or bone marrow progenitor cell transplantation;
  • Prior therapy with any known inhibitor of MNK1 or MNK2;
  • Prior high-dose chemotherapy requiring stem cell rescue;
  • History of or active autoimmune disorders or other conditions that might impair or compromise the immune system;
  • Any prior exposure to cytotoxic T-lymphocyte-associated protein 4 inhibitors;
  • Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids. Note: At Screening and during study participation, subjects may be using systemic corticosteroids (doses 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids;
  • Use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4 within 7 days prior to the start of Tomivosertib (eFT-508) or expected requirement for use of a strong CYP3A4 inhibitor or inducer during study participation; Need for proton pump inhibitors and histamine H2 blockers at study entry;
  • Previously received investigational product in a clinical trial within 30 days or within 5 elimination half-lives (whichever is longer) prior to the start of Tomivosertib (eFT-508), or is planning to take part in another clinical trial while participating in this study;
  • Has any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign Informed - Consent Document(s), adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results;
  • Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac - involvement of HCC based on imaging; or
  • Has had esophageal or gastric variceal bleeding within the last 6 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03616834


Contacts
Contact: Sarah Wheeler (858) 925-8215 swheeler@effector.com

Locations
United States, California
Pacific Shores Medical Group Recruiting
Long Beach, California, United States, 90813
Contact: Irene De Jesus    562-590-0345    irened@pacshoresoncology.com   
Principal Investigator: Nishan Tchekmedyian, MD         
St. Joseph Heritage Healthcare Recruiting
Santa Rosa, California, United States, 95403
Contact: Camille Shaffer    707-521-3809    camille.shaffer@stjoe.org   
Principal Investigator: Thomas Stanton, MD         
United States, Georgia
Columbus Regional Research Institute Recruiting
Columbus, Georgia, United States, 31904
Contact: Courtney Alexander    706-660-6449    calexander@iacthealth.com   
Principal Investigator: Andrew Pippas, MD         
United States, Idaho
Saint Alphonsus Regional Medical Center Recruiting
Boise, Idaho, United States, 83706
Contact: Olga Bittner       olga.bittner@saintalphonsus.org   
Principal Investigator: Kerry Pulver, MD, PhD         
United States, Indiana
Indiana University Health Melvin & Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Suzanne Bailey    317-278-4694    subailey@iupui.edu   
Principal Investigator: Bert O'Neil, MD         
United States, Maryland
Anne Arundel Medical Center Recruiting
Annapolis, Maryland, United States, 21401
Contact: Steven DeMartino    443-481-4390    sdemartino@aahs.org   
Principal Investigator: Peter Graze, MD         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Sarah Chalabi    313-576-8993    chalabis@karmanos.org   
Principal Investigator: Amy Weise, DO         
United States, Ohio
Universty of Toledo Medical Center Recruiting
Toledo, Ohio, United States, 43614
Contact: Stephanie Smiddy    419-383-6962    stephanie.smiddy@utoledo.edu   
Principal Investigator: John Nemunaitis         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Melissa Pomeroy    503-215-2714    melissa.pomeroy@providence.org   
Principal Investigator: Rachel Sanborn, MD         
United States, South Carolina
Spartanburg Medical Center Recruiting
Spartanburg, South Carolina, United States, 29303
Contact: Ken Kuenzli    864-560-6812    kkuenzli@gibbscc.org   
Principal Investigator: Vikas Demblas, MD         
United States, South Dakota
Avera Cancer Institute Recruiting
Sioux Falls, South Dakota, United States, 57105
Contact: Karin Swenson    605-322-3018    karin.swenson@avera.org   
Principal Investigator: Benjamin Solomon, MD         
United States, Virginia
Virginia Cancer Specialists, PC Recruiting
Fairfax, Virginia, United States, 22031
Contact: Claudia Phillips    703-208-9268    claudia.phillips@usoncology.com   
Principal Investigator: Alexander Spira, MD         
United States, Wisconsin
University of Wisconsin Clinical Science Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Jennifer Collins    608-265-0811    jennifer.collins@wisc.edu   
Principal Investigator: Nataliya Uboha, MD, PhD         
Sponsors and Collaborators
Effector Therapeutics
Investigators
Study Chair: Jeremy Barton, MD eFFECTOR Therapuetics

Responsible Party: Effector Therapeutics
ClinicalTrials.gov Identifier: NCT03616834     History of Changes
Other Study ID Numbers: eFT508-0010
First Posted: August 6, 2018    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No