A Phase I, Open-Label Study of GSK1795091 Administered in Combination with Immunotherapies in Participants with Advanced Solid Tumors.

Completed

Conditions: Advanced Solid Tumors
cancer

Registration Number: NL-OMON46814

Lead Sponsor: GlaxoSmithKline

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 4

Inclusion Criteria

1. Participant must be *18 years of at the time of signing the informed consent.
2. Histological documentation of advanced solid tumor, other than TNBC (defined per ASCO/CAP guidelines) [Hammond, 2010; Wolff, 2013].
3. Archival tumor tissue obtained at any time from the initial diagnosis to study entry. Although a fresh biopsy obtained during screening is preferred, archival tumor specimen is acceptable if it is not feasible to obtain a fresh biopsy.
Note: Participants enrolled in a PK/Pharmacodynamic Cohort must provide a fresh biopsy of a tumour lesion not previously irradiated during the screening period and must agree to provide at least one additional on-treatment biopsy.
4. Disease that has progressed after standard therapies or for which standard therapy is otherwise unsuitable (e.g., intolerance).
5. Measurable disease, i.e., presenting with at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
7. Life expectancy of at least 12 weeks.
8. Adequate organ function
9. applicable for France only
10. Male or female
a. Female participants:
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
i. Not a woman of childbearing potential (WOCBP)
OR
ii. A WOCBP who agrees to follow the contraceptive guidance
during the treatment period and for at least 120 days after the last dose of study treatment.
11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Additional Inclusion Criteria for Patients in Part 2
12. Histological or cytological documentation of SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) that is recurrent, locally advanced, or metastatic and is not amenable to curative treatment options, surgery or definitive chemoradiation therapy.
13. Received or ineligible for platinum-based therapy and PD-1/PD-L1 therapy.
14. Received no more than 3 prior lines of systemic therapy for metastatic disease.

Exclusion Criteria

1. Malignancy other than disease under study with the exception of those from which the participant has been disease-free for more than 2 years and not expected to affect the safety of the participant or the endpoints of the trial.
2. Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment.
3. Active autoimmune disease that has required systemic disease modifying or immunosuppressive treatment within the last 2 years.
Note: Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted.
4. Concurrent medical condition requiring the use of systemic immunosuppressive treatment within 28 days before the first dose of study treatment.
5. Known human immunodeficiency virus infection.
6. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis.
NOTE: Stable chronic liver disease (including Gilbert*s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria.
7. Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study treatment
8. Positive Hepatitis C test result at screening or within 3 months prior to first dose of study treatment.
NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
9. QTcF >450 msec or QTcF >480 msec for participants 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.
10. Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
11. Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.
12. History of severe hypersensitivity to mAbs.
13. History or evidence of cardiovascular (CV) risk including any of the following:
* Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second degree (Type II) or third degree atrioventricular block.
* Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrollment.
* Congestive heart failure (Class II, III, or IV) as defined by the New York
Heart Association functional classification system [NYHA, 1994].
* Recent (within the past 6 months) history of symptomatic pericarditis.
14. History of idiopathic pulmonary fibrosis, pneumonitis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis. 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 Sponsor.
15. Recent history (w

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>AEs, SAEs, DLTs, withdrawals due to AEs, dose reductions or delays, and changes<br /><br>in safety assessments (e.g., laboratory parameters, vital signs, and cardiac<br /><br>parameters).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>-Objective response rate (ORR) and disease control rate (DCR)<br /><br>(complete response [CR]+ partial response [PR]+ stable disease [SD] <br /><br>12 weeks), time to response, duration of response, progression-free<br /><br>survival (PFS), and overall survival.<br /><br>- GSK1795091 concentrations in plasma and assessment of PK<br /><br>parameters (e.g., maximum observed concentration [Cmax], AUC(0-)<br /><br>and trough plasma concentration [Ctrough]) if data permit.<br /><br>- Number and percentage of participants who develop detectable antidrug<br /><br>antibodies against GSK3174998, GSK3359609, or pembrolizumab.</p><br>