Primary:To determine the safety, tolerability, MTD (maximum tolerated dose) or the MAD (maximum administered dose) of GSK3359609 in combination with pembrolizumab or chemotherapy with(out) pembrolizumab. Secondary:To determine the recommended dose…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
solide tumoren
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Adverse events, dose limiting toxicities, dose modifications, PK and PD
activity.
Secondary outcome
Overall response rate (ORR), disease controll rate (DCR), progression free
survival (PFS), overall survival (OS), Time to response (TTR), duration of
response (DoR).
Background summary
GSK3359609 is an anti-Inducible T cell Co-Stimulator (ICOS) receptor agonist
antibody intended for the treatment of cancers of different histology. It is
expected to differentiate from first generation immunomodulatory antibodies
directed against immune checkpoint modulators by targeting a different axis in
the antitumor T cell response cascade and promoting activation of a
co-stimulatory receptor instead of blocking an inhibitory checkpoint receptor.
The desired pharmacology of GSK3359609 is to expand the total number and
increase the activity of tumor specific effector CD4+ and CD8+ T cell
populations. Tumor specific T cells must be first primed through contact with
cognate antigens and activated into effector cells in order for induction of
ICOS expression to occur and GSK3359609 to bind and elicit an agonist effect.
Therefore, it is expected that GSK3359609 will be most active in disease
settings where an antitumor immune response is primed as an inherent feature of
the tumor or by prior lines of therapy. Additionally, GSK3359609 is expected
to be active in combination with agents which prime or modulate tumor immunity.
Therefore, both single agent therapy and combination therapies will be
evaluated in the first-time-in-human clinical study.
Amendment 03: most important change: addition of an arm with standard
chemotherapy (part 2A).
Amendment 04: most important changes:
- Included background info on GSK3174998 (OX40) in support of the combination
with GSK3359609.
- Change study design: included the combination of GSK3359609 and GSK3174998
(OX40); combination offluorouracil (5-FU)/platinum with GSK3359609; combination
of GSK3359609 with pembrolizumab and the platinum doublets.
- NB: the dose escalation of GSK3359609 monotherapy has been closed in the
mean time according to plan.
Amendment 05: most important changes:
- Increased number of subjects from 500 to 698.
- In Part 2A chemotherapy safety cohort for 5-FU/platinum combination with
GSK3359609 and pembrolizumab, only subjects with HNSCC that was diagnosed as
recurrent or metastatic and considered incurable by local therapies, are
eligible.
- In Part 2A 5-FU/platinum combination with GSK3359609 and pembrolizumab
cohort, subjects must not have received prior systemic therapy administered in
the recurrent or metastatic setting.
Amendment 06 and 07: most important changes:
- Added HNSCC combination cohort of GSK3359609 and pembrolizumab for subjects
with CPS < 1
- Added investigation of GSK3359609 and pembrolizumab Q6W as a new HNSCC
randomized cohort
- Updated safety data GSK3359609 and pembrolizumab
- Option for restart of study medication after disease progression
- Total number of subjects increased to 798
Amendment 8: most important changes:
- Adjusted the total number of subjects that will be enrolled in the study to
847 and appropriate corresponding changes were added.
- Dostarlimab, cobolimab, and bintrafusp alfa cohorts has been removed.
Amendment 9: most impotant changes:
- Pembrolizumab: Eliminate collection of pharmacokinetics and anti-drug
antibody (ADA) bloodsample collections
- Eliminate collection of blood and tumor biomarker sample collections
- Eliminate all Patient Reported Outcome assessments
- Eliminate option for second course of therapy following relapse
- Updates to End of Study and Follow-up assessments
- Clarification of reporting process for hepatic toxicity
- The planned number of patients in the OX-40 cohort has been reached, so no
more patients will be allocated.
Study objective
Primary:
To determine the safety, tolerability, MTD (maximum tolerated dose) or the MAD
(maximum administered dose) of GSK3359609 in combination with pembrolizumab or
chemotherapy with(out) pembrolizumab.
Secondary:
To determine the recommended dose and schedule for further exploration,
antitumor activity, pharmacokinetic (PK) properties, immunogenicity.
Study design
Open-label, multicenter first in human study of IV administered GSK3359609. The
study will be conducted in two parts with each part consisting of a dose
escalation phase (A) and dose expansion phase (B). Part 1 will evaluate
GSK3359609 as a monotherapy, while Part 2 will evaluate GSK3359609 in
combination with pembrolizumab or chemotherapy with(out) pembrolizumab.
Treatment until disease progression, unacceptable toxicity, or withdrawal of
consent up to a maximum of duration of treatment for two years. Follow-up
period for safety assessments at least 90 days after last dose of study
treatment or until the start of subsequent anti-cancer treatment. Subjects will
be followed every 6 months for survival and subsequent anti-cancer therapy for
up to two years.
A total of up to approximately 867 subjects.
Intervention
Treatment with GSK3359609 monotherapy (part 1B) or GSK3359609 in combination
with pembrolizumab or OX40 or chemotherapy with(out) pembrolizumab.
Study burden and risks
Risk: Adverse events of the study medication. First in human study.
Burden:
• 11 visits during the first 2 months. Thereafter every 3 weeks. After
discontinuation of study medication visit months 1, 3, 6 and every 6 months
thereafter.
Based on 18 study weeks:
• 7 times IV infusions with GSK3359609 in combination with pembrolizumab, OX40
or chemotherapy with(out) pembrolizumab.
• Physical examination: 8 times.
• Blood draws: 15 times. 5-120 mL blood per occasion. Most blood is taken
during the first 3 months: approx. 475 mL in total. PK sampling days (once 8
samples in 8 hours, 5 times 2 samples, pre and post IV infusion). After
implementation of protocol amendment 9: 5 ml blood per visit. No more samples
for PK and ADA pembrolizumab or biomarkers.
• ECG: 6 times.
• CT/MRI scan every 9-12 weeks.
• Tumor biopsy: 0-1 (part A), 2 times (part B). After implementation of
protocol amendment 9: No more tissue biopsies.
' Questionnares (2) 8 times. After implementation of protocol amendment
9: No more questionnaires.
Optional:
• Blood sample for pharmacogenetics (6 mL).
• Tumor biopsy: 3-4 times (part A), 1-2 (part B). After implementation of
protocol amendment 9: No more tissue biopsies.
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Van Asch van Wijckstraat 55H
Amersfoort 3811 LP
NL
Listed location countries
Age
Inclusion criteria
• Male or female, age 18 years and above.
• Histological or cytological documentation of an invasive malignancy that was
diagnosed as locally advanced/metastatic or relapsed/refractory and is of one
of the tumor types:mentioned in chapter 5.1, item 3 of the protocol.
• Disease progressed after standard therapy for the specific tumor type, or
standard therapy was ineffective, intolerable, or inappropriate, or if no
further standard therapy exists. See protocol chapter 5.1, item 4 for details.
• Agree to undergo a pre-treatment and on treatment biopsy and have disease
amenable to biopsy required in PK/PD dose expansion cohorts.
• Measurable disease.
• ECOG performance status 0-1.
• Life expectancy of at least 12 weeks.
• Not pregnant or postmenopausal females and females of non-reproductive
potential or Reproductive potential and agrees to follow a required
contraceptive method (see protocol chapter 5.1, item 12 for details).
• Male subjects with female partners of child bearing potential who agree to
use one of the required methods of contraception.
Exclusion criteria
• Prior cancer and non-cancer treatment, see protocol chapter 5.2, item 1, 6, 7
for details.
• Bone marrow transplantation or other solid organ transplantation.
• CNS metastases. Exception: see protocol chapter 5.2, item 5 for details.
• Active autoimmune disease (refer to Appendix 2) that has required systemic
treatment within the last 2 years. Replacement therapy is not considered a form
of systemic treatment.
• Medical condition requiring the use of systemic immunosuppressive medications
within 28 days before the first dose of study treatment. Physiologic doses of
corticosteroids for treatment of endocrinopathies or steroids with minimal
systemic absorption may be continued if the subject is on a stable dose.
• Active infection, known human immunodeficiency virus infection, or positive
test for hepatitis B or hepatitis C.
• Current active liver or biliary disease (exceptions see protocol chapter 5.2,
item 12).
• Within the past 6 months: acute diverticulitis, inflammatory bowel disease,
intra-abdominal abscess, or gastrointestinal obstruction.
• Live vaccine within 4 weeks.
• Allergen desensitization therapy within 4 weeks.
• History or evidence of cardiac and pulmonary abnormalities (see protocol
chapter 5.2, items 17, 18 for details).
• Within 6 months: uncontrolled symptomatic ascites or pleural effusions.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-000148-32-NL |
| CCMO | NL58480.031.16 |
| Other | www.gskclinicalstudyregister.com, nummer 204691 |