GSK3359609 Plus Tremelimumab for the Treatment of Advanced Solid Tumors
Sponsor:
GlaxoSmithKline
Collaborators:
Information provided by (Responsible Party):
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| Tracking Information | |||
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| First Submitted Date ICMJE | October 1, 2018 | ||
| First Posted Date ICMJE | October 3, 2018 | ||
| Last Update Posted Date | October 3, 2018 | ||
| Actual Study Start Date ICMJE | December 3, 2018 | ||
| Estimated Primary Completion Date | June 23, 2022 (Final data collection date for primary outcome measure) | ||
| Current Primary Outcome Measures ICMJE |
Number of subjects with dose limiting toxicities (DLTs)-Part 1[ Time Frame: Up to 28 days ] An adverse event (AE) is considered to be a DLT if it is considered by the investigator to be clinically relevant and is attributed to the study treatment during the 28-day DLT observation period and meets at least 1 of the pre-specified criteria. Severity of DLTs-Part 1[ Time Frame: Up to 28 days ] The severity of all toxicities will be graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Number of subjects with AEs, serious adverse events (SAEs) and adverse events of significant importance (AESI)-Part 1[ Time Frame: Up to 4 years ] An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention/SOC, whether or not considered related to the study intervention/SOC. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the subject or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before. Number of subjects with AE/SAE/DLTs leading to dose modifications/delays/withdrawals-Part 1[ Time Frame: Up to 4 years ] The number of subjects with AE/SAE/DLTs leading to dose modifications/delays/withdrawals will be summarized. Severity of AEs, SAEs, AESI and AE/SAE/DLTs leading to dose modifications/delays/withdrawals-Part 1[ Time Frame: Up to 4 years ] The severity of all toxicities will be graded using the NCI-CTCAE (version 5.0). Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)-Part 1[ Time Frame: Baseline and up to 2 years ] SBP and DBP will be measured after 5 minutes of rest for the subject. Change from Baseline in temperature-Part 1[ Time Frame: Baseline and up to 2 years ] Temperature will be measured after 5 minutes of rest for the subject. Change from Baseline in pulse rate-Part 1[ Time Frame: Baseline and up to 2 years ] Pulse rate will be measured after 5 minutes of rest for the subject. Change from Baseline in respiratory rate-Part 1[ Time Frame: Baseline and up to 2 years ] Respiratory rate will be measured after 5 minutes of rest for the subject. Change from Baseline in oxygen saturation-Part 1[ Time Frame: Baseline and up to 2 years ] Oxygen saturation will be measured using pulse oximetry after 5 minutes of rest for the subject. Change from Baseline in electrocardiogram (ECG) measurement-Part 1[ Time Frame: Baseline and Day 1 ] Single 12-lead ECG will be obtained using an automated ECG machine. Change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count. Change from Baseline in hemoglobin level-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in hemoglobin level. Change from Baseline in hematocrit level-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in hematocrit level. Change from Baseline in red blood cell (RBC) count-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in RBC count. Change from Baseline in albumin and total protein levels-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in albumin and total protein levels. Change from Baseline in creatinine and bilirubin levels-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in creatinine and bilirubin levels. Change from Baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), amylase and lipase levels-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in ALT, AST ALP, LDH, amylase and lipase levels. Change from Baseline in blood urea nitrogen (BUN), glucose, potassium, sodium and calcium-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change in levels of BUN, glucose, potassium, sodium and calcium from Baseline. Change from Baseline in specific gravity of urine-Part 1[ Time Frame: Baseline and up to 2 years ] Urine samples will be collected to assess change from Baseline in specific gravity of urine. Change from Baseline in potential of hydrogen (pH) of urine-Part 1[ Time Frame: Baseline and up to 2 years ] Urine samples will be collected to assess change from Baseline in pH of urine. Change from Baseline in glucose, protein, blood and ketone levels in urine-Part 1[ Time Frame: Baseline and up to 2 years ] Urine samples will be collected to assess change from Baseline in glucose, protein, blood and ketone levels in urine . Change from Baseline in thyroxine stimulating hormone (TSH)-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in TSH. Change from Baseline in free triiodothyronine (T3)-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in free T3. Change from Baseline in free thyroxine (T4)-Part 1[ Time Frame: Baseline and up to 2 years ] Blood samples will be collected to assess change from Baseline in free T4. Overall survival-Part 2[ Time Frame: Up to 4 years ] For subjects in Part 2, overall survival is defined as time from the date of randomization to the date of death due to any cause. |
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| Original Primary Outcome Measures ICMJE | Same as current | ||
| Current Secondary Outcome Measures ICMJE |
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| Descriptive Information | |||
| Brief Title ICMJE | GSK3359609 Plus Tremelimumab for the Treatment of Advanced Solid Tumors |
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| Official Title ICMJE | A Phase I/II, Open-label, Two Part Study of GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors |
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| 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. |
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| Detailed Description | |||
| Study Type ICMJE | Interventional | ||
| Study Phase | Phase 2 | ||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: In Part 1, dose escalation will occur using a zone based approach. Part 2 will be randomized, parallel group study wherein the subjects will be randomized in a ratio of 2:1 to either recommended Phase 2 dose combination of GSK3359609 and tremelimumab or SOC (paclitaxel, docetaxel or cetuximab). Masking: Interventional Masking Description: Primary Purpose: Treatment |
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| Condition ICMJE | |||
| Intervention ICMJE |
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| Study Arms |
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| Recruitment Information | |||
| Recruitment Status ICMJE | Not yet recruiting | ||
| Estimated Enrollment ICMJE |
115 | ||
| Original Estimated Enrollment ICMJE | Same as current | ||
| Estimated Study Completion Date | June 23, 2022 | ||
| Estimated Primary Completion Date | June 23, 2022 (Final data collection date for primary outcome measure) | ||
| Eligibility Criteria ICMJE | 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. | ||
| Sex/Gender |
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| Ages | 18 Years and older (Adult, Older Adult) | ||
| Accepts Healthy Volunteers | No | ||
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| Administrative Information | Has Data Monitoring Committee | No | |
| U.S. FDA-regulated Product |
Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No |
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| IPD Sharing Statement |
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| Responsible Party | ， | ||
| Study Sponsor ICMJE | GlaxoSmithKline | ||
| Collaborators ICMJE | |||
| Investigators ICMJE |
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| PRS Account | |||
| Verification Date | October 2018 | ||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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