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BRIEF TITLE: GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors

A Phase I/II, Open-label, Two Part Study of GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors


  • Org Study ID: 207871
  • Secondary ID:
  • NCT ID: NCT03693612
  • NCT Alias:
  • Sponsor: GlaxoSmithKline - Industry
  • Source: GlaxoSmithKline

Brief Summary

The purpose of this study is to evaluate if the combination of GSK3359609 and tremelimumab is safe and tolerable (Part 1) and provides significant survival benefit to subjects with relapsed/refractory (R/R) Head and Neck Squamous Cell Carcinomas (HNSCC) to warrant further clinical investigation (Part 2). Part 1 (dose escalation) will enroll subjects with advanced, selected solid tumors. Subjects will receive escalating doses of GSK3359609 and tremelimumab in combination in Part 1. Part 2 is randomized expansion and will enroll subjects with R/R HNSCC who have disease progression after receiving at least 1 platinum-based chemotherapy and at least 1 anti-programmed death receptor protein-1 (PD-1)/anti-programmed death-ligand 1 (PD-L1) therapy, whether in combination or separately. In Part 2, subjects will be randomized in a ratio of 2:1 to receive either GSK3359609 in combination with tremelimumab at the recommended Phase 2 dose or investigators choice of a single-agent standard of care (SOC) therapy including paclitaxel, docetaxel or cetuximab. The total duration of subjects in the study will be approximately 4 years.

Overal Status Start Date Phase Study Type
Recruiting November 26, 2018 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Number of subjects with dose limiting toxicities (DLTs)-Part 1

Primary Outcome 1 - Time Frame: Up to 28 days

Primary Outcome 2 - Measure: Severity of DLTs-Part 1

Primary Outcome 2 - Time Frame: Up to 28 days

Primary Outcome 3 - Measure: Number of subjects with AEs, serious adverse events (SAEs) and adverse events of significant importance (AESI)-Part 1

Primary Outcome 3 - Time Frame: Up to 4 years

Primary Outcome 4 - Measure: Number of subjects with AE/SAE/DLTs leading to dose modifications/delays/withdrawals-Part 1

Primary Outcome 4 - Time Frame: Up to 4 years

Primary Outcome 5 - Measure: Severity of AEs, SAEs, AESI and AE/SAE/DLTs leading to dose modifications/delays/withdrawals-Part 1

Primary Outcome 5 - Time Frame: Up to 4 years

Primary Outcome 6 - Measure: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)-Part 1

Primary Outcome 6 - Time Frame: Baseline and up to 2 years

Primary Outcome 7 - Measure: Change from Baseline in temperature-Part 1

Primary Outcome 7 - Time Frame: Baseline and up to 2 years

Primary Outcome 8 - Measure: Change from Baseline in pulse rate-Part 1

Primary Outcome 8 - Time Frame: Baseline and up to 2 years

Primary Outcome 9 - Measure: Change from Baseline in respiratory rate-Part 1

Primary Outcome 9 - Time Frame: Baseline and up to 2 years

Primary Outcome 10 - Measure: Change from Baseline in oxygen saturation-Part 1

Primary Outcome 10 - Time Frame: Baseline and up to 2 years

Primary Outcome 11 - Measure: Change from Baseline in electrocardiogram (ECG) measurement-Part 1

Primary Outcome 11 - Time Frame: Baseline and Day 1

Primary Outcome 12 - Measure: Change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count-Part 1

Primary Outcome 12 - Time Frame: Baseline and up to 2 years

Primary Outcome 13 - Measure: Change from Baseline in hemoglobin level-Part 1

Primary Outcome 13 - Time Frame: Baseline and up to 2 years

Primary Outcome 14 - Measure: Change from Baseline in hematocrit level-Part 1

Primary Outcome 14 - Time Frame: Baseline and up to 2 years

Primary Outcome 15 - Measure: Change from Baseline in red blood cell (RBC) count-Part 1

Primary Outcome 15 - Time Frame: Baseline and up to 2 years

Primary Outcome 16 - Measure: Change from Baseline in albumin and total protein levels-Part 1

Primary Outcome 16 - Time Frame: Baseline and up to 2 years

Primary Outcome 17 - Measure: Change from Baseline in creatinine and bilirubin levels-Part 1

Primary Outcome 17 - Time Frame: Baseline and up to 2 years

Primary Outcome 18 - Measure: Change from Baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), amylase and lipase levels-Part 1

Primary Outcome 18 - Time Frame: Baseline and up to 2 years

Primary Outcome 19 - Measure: Change from Baseline in blood urea nitrogen (BUN), glucose, potassium, sodium and calcium-Part 1

Primary Outcome 19 - Time Frame: Baseline and up to 2 years

Primary Outcome 20 - Measure: Change from Baseline in specific gravity of urine-Part 1

Primary Outcome 20 - Time Frame: Baseline and up to 2 years

Primary Outcome 21 - Measure: Change from Baseline in potential of hydrogen (pH) of urine-Part 1

Primary Outcome 21 - Time Frame: Baseline and up to 2 years

Primary Outcome 22 - Measure: Change from Baseline in glucose, protein, blood and ketone levels in urine-Part 1

Primary Outcome 22 - Time Frame: Baseline and up to 2 years

Primary Outcome 23 - Measure: Change from Baseline in thyroxine stimulating hormone (TSH)-Part 1

Primary Outcome 23 - Time Frame: Baseline and up to 2 years

Primary Outcome 24 - Measure: Change from Baseline in free triiodothyronine (T3)-Part 1

Primary Outcome 24 - Time Frame: Baseline and up to 2 years

Primary Outcome 25 - Measure: Change from Baseline in free thyroxine (T4)-Part 1

Primary Outcome 25 - Time Frame: Baseline and up to 2 years

Primary Outcome 26 - Measure: Overall survival-Part 2

Primary Outcome 26 - Time Frame: Up to 4 years

Condition:

  • Neoplasms

Eligibility

Criteria:
Inclusion Criteria:

- Capable of giving signed informed consent/assent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and protocol.

- Male or female, aged 18 years or older.

- Body weight >=30 kilograms (kg).

- Histological or cytological documentation of an invasive malignancy that was diagnosed
as locally advanced/metastatic or relapsed/refractory and is of one of the following
tumor types: a) Part 1: cutaneous melanoma; HNSCC (oral cavity, larynx, oropharynx,
hypopharynx, nasal cavity/paranasal sinuses); non-small cell lung cancer (squamous and
non-squamous); urothelial carcinoma of the upper and lower urinary tract; clear cell
renal carcinoma; castrate resistant prostate adenocarcinoma. b) Part 2: HNSCC (oral
cavity, larynx, pharynx, paranasal sinuses).

- Part 1 only: 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, or where standard
therapy is refused. May be anti-PD-1/anti-PD-L1 experienced or naïve.

- Part 2 only: Disease that has progressed after receiving platinum-based chemotherapy
(unless medically contraindicated or discontinued due to toxicity) and
anti-PD-1/anti-PD-L1 therapy (in combination or as separate lines of therapy in either
sequence).

- Measurable disease per RECIST version 1.1 guidelines. 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 unless agreed upon by GlaxoSmithKline (GSK).

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.

- Adequate organ function.

- A female subject is eligible to participate if she is not pregnant, not breastfeeding,
and at least one of the following conditions apply: a) Not a woman of childbearing
potential (WOCBP); or, b) A WOCBP who agrees to follow the contraceptive while
receiving study intervention and for at least 180 days after the last dose of study
intervention.

- A male subject must agree to use a highly effective contraception while receiving
study intervention and for at least 180 days after the last dose of study intervention
and refrain from donating sperm during this period.

- Agree to collection of tumor tissue: a) Part 1 and Part 2: Archival tumor tissue
collected any time from the initial diagnosis of invasive malignancy; a fresh tumor
biopsy will be required if archival specimen is unavailable prior to first dose. b)
Part 1 pharmacokinetic/pharmacodynamic cohort(s): Archival tissue as noted in point
(a) above. Paired tumor biopsies: tumor tissue collected any time after completion of
dosing of the last therapy and prior to first dose and an on-treatment biopsy. c) Part
2: A minimum of 15 subjects from each arm will be required to provide paired tumor
biopsies (in addition to the archival tissues as noted in point (a) above): tumor
tissue collected any time after completion of dosing of the last therapy and prior to
first dose and an on-treatment biopsy.

Exclusion Criteria:

- Received prior treatment with the following therapies; calculation is based on date of
last therapy to date of first dose of study intervention or SOC: a) Cytotoxic
T-Lymphocyte-Associated Protein 4 (CTLA-4 [including tremelimumab] or Inducible T Cell
Co-Stimulator (ICOS)-directed therapies at any time; b) >=4 lines of prior anticancer
treatment: In subjects that relapse or progress within 1 year from the beginning of
adjuvant or concurrent therapy, the adjuvant/concurrent therapy is considered first
line therapy; c) Systemic anticancer therapy or investigational therapy within 30
days, or 5 half-lives, whichever is shorter; at least 14 days must have elapsed
between the date of the last prior therapy to the date of first dose of study
intervention or SOC.

- Prior radiation therapy: permissible if at least one non-irradiated measurable lesion
is available for assessment per RECIST v1.1 or if a solitary measurable lesion was
irradiated, objective progression is documented. At least 14 days must have elapsed
between the date of the last dosage of radiation and the first dose of study
intervention/SOC.

- Invasive malignancy or history of invasive malignancy other than disease under study
within the last two years, except: a) Any other invasive malignancy for which the
subject was definitively treated, has been disease-free for <=2 years and in the
opinion of the Investigator and Medical Monitor will not affect the evaluation of the
effects of the study intervention or SOC on the currently targeted malignancy, may be
included in this clinical study; Curatively treated non-melanoma skin cancer or
successfully treated in-situ carcinoma.

- Toxicity from previous anticancer treatment that includes: a) >=Grade 3 toxicity
considered related to prior immunotherapy and that led to treatment discontinuation;
b) Toxicity related to prior treatment that has not resolved to <=Grade 1 (except
alopecia, vitiligo, hearing loss, endocrinopathy managed with replacement therapy, and
peripheral neuropathy which must be <=Grade 2).

- Central nervous system (CNS) metastases, with the following exception: Subjects with
previously treated CNS metastases who are clinically stable and had no requirement for
steroids during at least 14 days prior to first dose of study intervention or SOC.

- Major surgery <=28 days of first dose of study intervention or SOC.

- Autoimmune disease (current or history) or syndrome that required systemic treatment
within the past 2 years. Replacement therapies which include physiological doses of
corticosteroids for treatment of endocrinopathies (i.e., adrenal insufficiency) are
not considered systemic treatments.

- Recent history (within 24 weeks) of gastrointestinal obstruction that required
surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess.

- Receiving systemic steroids (>=10 milligrams [mg] oral prednisone or equivalent) or
other immunosuppressive agents within 7 days prior to first dose of study intervention
or SOC.

- Prior allogeneic/autologous bone marrow or solid organ transplantation.

- Received live-virus vaccine within 30 days from start of study intervention or SOC.

- Current or history of idiopathic pulmonary fibrosis, pneumonitis (for past, subject is
excluded if steroids were required), interstitial lung disease or organizing
pneumonia.

- Recent history (within 24 weeks) of uncontrolled, symptomatic ascites, pleural or
pericardial effusions.

- History or evidence of cardiac abnormalities within the 24 weeks prior to enrollment
which include: a) Serious uncontrolled cardiac arrhythmia or clinically significant
electrocardiogram abnormalities including second degree (Type II) or third degree
atrioventricular block. b) Cardiomyopathy, myocardial infarction, acute coronary
syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or
bypass grafting. c) Symptomatic pericarditis.

- Current unstable liver or biliary disease per Investigator assessment defined by the
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
gastric varices, persistent jaundice, or cirrhosis.

- Active infection requiring systemic therapy.

- Known human immunodeficiency virus infection; positive test for hepatitis B active
infection (presence of hepatitis B surface antigen) or hepatitis C active infection.

- History of severe hypersensitivity to monoclonal antibodies, the Standard of Care
agents, including any ingredient used in the formulation, based on which treatment the
subject is to receive.

- Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric
disorder, or other conditions that could interfere with subject's safety, obtaining
informed consent or compliance to the study procedures, in the opinion of the
Investigator.

- For subjects receiving SOC: Requires therapy with a medication that may alter the PK
of the SOC agent (e.g., strong inducers or inhibitors of cytochrome P (CYP)3A4 for
subjects receiving docetaxel or paclitaxel) during the study treatment period. Please
refer to the package insert for the agent the subject is to receive.

- For subjects receiving SOC: Any contraindication, per the package insert and/or
Institutional guidelines, to the treatment the subject is to receive.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: GSK Clinical Trials

Role: Study Director

Affiliation: GlaxoSmithKline

Overall Contact

Name: US GSK Clinical Trials Call Center

Phone: 877-379-3718

Email: GSKClinicalSupportHD@gsk.com

Locations

Facility Status Contact
GSK Investigational Site
Boston, Massachusetts 02215
United States
Recruiting US GSK Clinical Trials Call Center
877-379-3718
GSKClinicalSupportHD@gsk.com
GSK Investigational Site
New York, New York 10016-4744
United States
Recruiting US GSK Clinical Trials Call Center
877-379-3718
GSKClinicalSupportHD@gsk.com
GSK Investigational Site
New York, New York 10032
United States
Recruiting US GSK Clinical Trials Call Center
877-379-3718
GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Pittsburgh, Pennsylvania 15232
United States
Recruiting US GSK Clinical Trials Call Center
877-379-3718
GSKClinicalSupportHD@gsk.com
GSK Investigational Site
San Antonio, Texas 78229
United States
Recruiting US GSK Clinical Trials Call Center
877-379-3718
GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Melbourne, Victoria 3000
Australia
Recruiting US GSK Clinical Trials Call Center
877-379-3718
GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Ottawa, Ontario K1H 8L6
Canada
Recruiting US GSK Clinical Trials Call Center
877-379-3718
GSKClinicalSupportHD@gsk.com
GSK Investigational Site
Toronto, Ontario M5G 2M9
Canada
Recruiting US GSK Clinical Trials Call Center
877-379-3718
GSKClinicalSupportHD@gsk.com