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Trial record 4 of 23 for:    agonist ICOS

Dose Escalation and Expansion Study of GSK3359609 in Subjects With Selected Advanced Solid Tumors (INDUCE-1)

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by GlaxoSmithKline
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02723955
First received: March 24, 2016
Last updated: April 24, 2017
Last verified: April 2017
  Purpose
GSK3359609 is an anti-Inducible T cell Co-Stimulator (ICOS) receptor agonist antibody intended for the treatment of cancers of different histology. This is a first-time-in-human (FTIH), open-label. multicenter study designed to investigate the safety, pharmacology, and preliminary antitumor activity in subjects with advanced or recurrent solid tumors with the aim to establish recommended dose(s) of GSK3359609 for further exploration as monotherapy and in combination with pembrolizumab or other immune therapies. The study is comprised of two primary parts, each composed of two phases: Part 1: GSK3359609 monotherapy with Part 1A as dose escalation phase and Part 1B as dose expansion phase; Part 2: GSK3359609 combination therapy with Part 2A dose escalation phase and Part 2B dose expansion phase. Each part and phase of the study includes a screening period, a treatment period, and a follow-up period. The primary objective of the study is to determine the safety, tolerability, maximum tolerated dose or the maximum administered dose of GSK3359609 alone or in combination.

Condition Intervention Phase
Cancer Drug: GSK3359609 IV infusion Drug: Pembrolizumab 200 mg IV infusion Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I Open Label Study of GSK3359609 Administered Alone and in Combination With Anticancer Agents in Subjects With Selected Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Parts 1 and 2: Number of subjects with any adverse event(s) (AE) and serious adverse event(s) (SAE) [ Time Frame: Up to 27 months ]
  • Parts 1 and 2: Changes in systolic and diastolic blood pressure [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Changes in pulse rate [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Changes in temperature [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Change in hematology parameters [ Time Frame: Up to 24 months ]
    The following hematology parameters will be measured: hemoglobin, Hematocrit, Red blood cell (RBC) count, Platelet count, white blood cell (WBC) count, Total neutrophils (Absolute), Eosinophils (Absolute), Monocytes (Absolute), Basophils (Absolute), and Lymphocytes (Absolute)

  • Parts 1 and 2: Change in chemistry parameters [ Time Frame: Up to 24 months ]
    The following chemistry parameters will be measured: Blood Urea nitrogen (BUN), Creatinine, Glucose, Calcium, Sodium, Potassium, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Bilirubin, Total protein and Albumin.

  • Parts 1 and 2: Change in urinalysis parameters [ Time Frame: Up to 24 months ]
    The following urinalysis parameters will be measured: pH, Glucose, Protein, Blood, Ketones by dipstick; and specific gravity

  • Parts 1 and 2: Change in thyroid function tests [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Number subject requiring dose modifications [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Number subject with dose limiting toxicity (DLT) [ Time Frame: First 28 days after the first dose of study treatment ]
    A DLT is defined as an AE that meets at least one of the criteria listed in protocol, according to National Cancer Institute (NCI) common terminology criteria for AE (CTCAE) grade (G) version 4.0, and is considered by the investigator to be clinically relevant and attributed (definitely, probably, or possibly) to the study treatment during the first 28 days after the first dose of study treatment.

  • Parts 1 and 2: Pharmacodynamic characteristics assessed as a measures of target engagement and functional effects in the tumor and in the periphery [ Time Frame: Up to 24 months ]
  • Parts 1 and 2: Plasma concentrations of GSK3359609 [ Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 64, 85, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of GSK3359609 (Up to 27 months). ]
  • Part 2: Plasma concentrations of pembrolizumab [ Time Frame: Days 1, 2, 8, 15, 22, 64, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of Pembrolizumab (Up to 27 months). ]
  • Parts 1 and 2: Change in echocardiogram [ Time Frame: Up to 24 months ]

Secondary Outcome Measures:
  • Parts 1 and 2: Disease control rate (DCR) [ Time Frame: Up to 24 months ]
    DCR is defined as the percentage of subjects with a confirmed complete response (CR) + partial response (PR) at any time, plus stable disease (SD) >=18 weeks)

  • Parts 1 and 2: Overall response rate (ORR) [ Time Frame: Up to 24 months ]
    ORR is defined as the percentage of subjects with a best overall confirmed CR or a PR at any time as per disease-specific criteria

  • Parts 1 and 2: Overall survival (OS) [ Time Frame: up to 4 years ]
    OS is defined as time from the date of first dose of study treatment to the date of death due to any cause.

  • Parts 1 and 2: Progression-free survival (PFS) [ Time Frame: Up to 24 months ]
    PFS is defined as time from the date of first dose of study treatment to the date of disease progression according to clinical or radiographic assessment or death due to any cause, whichever occurs earliest.

  • Parts 1 and 2: Time to overall response (TTR) [ Time Frame: Up to 24 months ]
    TTR will be summarized for subjects with a confirmed CR or PR and is defined as the time from date of first dose of study treatment to date of first documented confirmed CR or PR.

  • Parts 1 and 2: Duration of response (DOR) [ Time Frame: Up to 24 months ]
    DOR will be summarized for subjects with a confirmed CR or PR and is defined as the time from date of initial confirmed response to the date of disease progression or death due to any cause.

  • Part 1: Anti-drug antibody (ADA) incidence by GSK3359609 dose level [ Time Frame: Up to 27 months ]
  • Part 2: ADA incidence by GSK3359609 and pembrolizumab dose level [ Time Frame: Up to 27 months ]
  • Parts 1 and 2: Area under curve (AUC) from time curve over the dosing interval [ Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 64, 85, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of GSK3359609 (Up to 27 months) ]
  • Parts 1 and 2: Maximum observed plasma concentration (Cmax) of GSK3359609 [ Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 64, 85, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of GSK3359609 (Up to 27 months). ]
  • Part 1 and 2: Minimum observed plasma concentration (Cmin) of GSK3359609 [ Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 29, 36, 43, 64, 85, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of GSK3359609 (Up to 27 months). ]
  • Parts 1 and 2: AUC (0-tau) of Pembrolizumab [ Time Frame: Days 1, 2, 8, 15, 22, 64, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of Pembrolizumab (Up to 27 months) ]
  • Parts 1 and 2: Cmax of Pembrolizumab [ Time Frame: Days 1, 2, 8, 15, 22, 64, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of Pembrolizumab (Up to 27 months). ]
  • Parts 1 and 2: Cmin of Pembrolizumab [ Time Frame: Days 1, 2, 8, 15, 22, 64, 106, 127 and Week 21 from then every 12 weeks, and additionally at 30 days and 12 weeks post last dose of Pembrolizumab (Up to 27 months). ]

Estimated Enrollment: 304
Study Start Date: June 1, 2016
Estimated Study Completion Date: June 21, 2019
Estimated Primary Completion Date: June 1, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1A: Dose escalation GSK33596069
Subject will receive GSK3359609 as an intravenous (IV) infusion administered Q3W continuously at a dose level dependent on to which dose level the subject is accrued.
Drug: GSK3359609 IV infusion
GSK3359609 will be administered intravenously to the subjects. Diluted product will be administered as IV Infusion once Q3W
Experimental: Part 1B: Dose expansion GSK33596069
Subjects will receive GSK3359609 as an IV infusion administered Q3W continuously at a dose level chosen for further exploration in dose expansion cohorts.
Drug: GSK3359609 IV infusion
GSK3359609 will be administered intravenously to the subjects. Diluted product will be administered as IV Infusion once Q3W
Experimental: Part 2A: Dose escalation -GSK33596069
Subjects receive GSK3359609 as an IV infusion administered Q3W continuously in combination with either 200 milligram (mg) of pembrolizumab as an IV infusion administered once Q3W continuously or at the dosing schedule and duration established for the another immune therapy selected.
Drug: GSK3359609 IV infusion
GSK3359609 will be administered intravenously to the subjects. Diluted product will be administered as IV Infusion once Q3W
Drug: Pembrolizumab 200 mg IV infusion
Pembrolizumab 200 mg will be intravenously administered to subjects.
Experimental: Part 2B: Dose expansion-GSK33596069
Subjects receive GSK3359609 as an IV infusion administered Q3W continuously in combination with either 200 mg of pembrolizumab as an IV infusion administered once Q3W continuously or at the dosing schedule and duration established for the another immune therapy selected.
Drug: GSK3359609 IV infusion
GSK3359609 will be administered intravenously to the subjects. Diluted product will be administered as IV Infusion once Q3W
Drug: Pembrolizumab 200 mg IV infusion
Pembrolizumab 200 mg will be intravenously administered to subjects.

  Eligibility

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

Inclusion Criteria

  • Capable of giving signed, written informed consent
  • Male or female, age >=18 years (at the time consent is obtained).
  • Histological or cytological documentation of an invasive carcinoma that was diagnosed as locally advanced/metastatic or recurrent and is of one of the following tumor types: bladder; cervical; colorectal (includes appendix); esophagus, squamous cell; head and neck; melanoma; malignant pleural mesothelioma (MPM); non-small-cell lung cancer (NSCLC) and prostate
  • Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists. Subjects should not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies.
  • Archival tumor tissue obtained at anytime from the initial diagnosis to study entry; a fresh tumor biopsy will be required if archival tissue is unavailable.
  • Agree to undergo a pre-treatment and on treatment biopsy and have disease amenable to biopsy required in PK/pharmacodynamic dose expansion cohorts.
  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Palpable lesions that are not measurable by radiographic or photographic evaluations may not be utilized as the only measurable lesion. Any measurable lesion biopsied at Screening cannot be followed as a target/index lesion.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Life expectancy of at least 12 weeks.
  • Adequate organ function
  • QTcF <450 milliseconds (msec) or QTcF <480 msec for subjects with bundle branch block. The QTcF is the QT interval corrected for heart rate according to Fridericia's formula, machine-read or manually over-read.
  • A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum beta-human chorionic gonadotrophin [beta-hCG] test) in females of reproductive potential), not lactating or if of reproductive potential agrees to follow one of the options listed in protocol from 30 days prior to the first dose of study medication and until 120 days after the last dose of study treatment.
  • Male subjects with female partners of child bearing potential must agree to use one of the methods of contraception specified in protocol from time of first dose of study treatment until 120 days after the last dose of study treatment.

Exclusion Criteria

  • Prior treatment with the following therapies (from last dose of prior treatment to first dose of GSK3359609):

    • Anticancer therapy within 30 days or 5 half lives of the drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the first dose of study drug is administered.
    • Prior radiation therapy: permissible if at least one non-irradiated measurable lesion is available for assessment according to RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least two weeks before start of study drug for radiation of any intended use to the extremities for bone metastases and 4 weeks for radiation to the chest, brain, or visceral organs is required.
    • Investigational therapy within 30 days or 5 half-lives of the investigational product (whichever is shorter). At least 14 days must have elapsed between the last dose of investigational agent and the first dose of study drug is administered.
  • Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
  • Toxicity from previous anticancer treatment
  • Invasive malignancy or history of invasive malignancy other than disease under study
  • Central nervous system (CNS) metastases, with the following exception:

    • Subjects who have previously-treated CNS metastases, are asymptomatic, and have no requirement for steroids at least 14 days prior to first dose of study drug.

Note: Subjects with carcinomatous meningitis are excluded regardless of clinical stability.

  • Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, recombinant erythropoietin) within 14 days prior to the first dose of GSK3359609.
  • Major surgery <=4 weeks before the first dose of study treatment. Subjects must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.
  • Active autoimmune disease that has required systemic treatment within the last two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

    • Note: Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

  • Concurrent medical condition requiring the use of systemic immunosuppressive medications within 7 days before the first dose of study treatment. Physiologic doses of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic absorption, including topical, inhaled, or intranasal corticosteroids may be continued if the subject is on a stable dose.
  • Active infection requiring systemic therapy, known human immunodeficiency virus infection, or positive test for hepatitis B or hepatitis C.
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).
  • Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction
  • Receipt of any live vaccine within 4 weeks.
  • Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.
  • History of severe hypersensitivity to monoclonal antibodies.
  • History or evidence of cardiac abnormalities
  • History of (current and past) idiopathic pulmonary fibrosis, pneumonitis (for past pneumonitis exclusion only if steroids were required for treatment),interstitial lung disease, or organizing pneumonia. Note: post-radiation changes in the lung related to prior radiotherapy and/or asymptomatic radiation-induced pneumonitis not requiring treatment may be permitted if agreed by the investigator and Medical Monitor.
  • Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other condition that could interfere with the subject's safety, obtaining informed consent, or compliance to the study procedures.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02723955

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
United States, Tennessee
GSK Investigational Site Recruiting
Nashville, Tennessee, United States, 37203
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Australia, Victoria
GSK Investigational Site Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Melbourne, Victoria, Australia, 3000
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Australia, Western Australia
GSK Investigational Site Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Canada, Ontario
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
France
GSK Investigational Site Recruiting
Villejuif cedex, France, 94805
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Spain
GSK Investigational Site Not yet recruiting
Barcelona, Spain, 08035
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Madrid, Spain, 28040
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Merck Sharp & Dohme Corp.
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02723955     History of Changes
Other Study ID Numbers: 204691
Study First Received: March 24, 2016
Last Updated: April 24, 2017

Keywords provided by GlaxoSmithKline:
ICOS receptor agonist antibody
Pembrolizumab
KEYNOTE-478
GSK3359609
Dose expansion
Dose escalation

Additional relevant MeSH terms:
Pembrolizumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 21, 2017