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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02723955


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT02723955
Ethics application status
Date submitted
24/03/2016
Date registered
31/03/2016

Titles & IDs
Public title
Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1)
Scientific title
A Phase I Open Label Study of GSK3359609 Administered Alone and in Combination With Anticancer Agents in Subjects With Selected Advanced Solid Tumors
Secondary ID [1] 0 0
2016-000148-32
Secondary ID [2] 0 0
204691
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Part 1A: Dose escalation feladilimab (GSK3359609) - Participants will receive feladilimab (GSK3359609) administered continuously at a dose level dependent on to which dose level the participant is accrued.

Experimental: Part 1B: Expansion feladilimab (GSK3359609) - Participants will receive feladilimab (GSK3359609) administered continuously at a dose level chosen for further exploration in dose expansion cohorts.

Experimental: Part 2A: Dose escalation (feladilimab (GSK3359609)+pembrolizumab) - Participants will receive feladilimab (GSK3359609) administered continuously in combination with pembrolizumab.

Experimental: Part 2A: Dose escalation (feladilimab (GSK3359609)+GSK3174998) - Participants will receive feladilimab (GSK3359609) administered continuously in combination with GSK3174998.

Experimental: Part 2A: Safety run-in (feladilimab (GSK3359609)+chemotherapy) - Participants participating in Part 2A chemotherapy combination cohorts will receive feladilimab (GSK3359609) in combination with chemotherapy at doses and schedules based on standard of care practice.

Experimental: Part 2B: Expansion-feladilimab (GSK3359609) - Participants will receive feladilimab (GSK3359609) administered continuously in combination with pembrolizumab.

Experimental: Part 2A: Dose escalation (feladilimab (GSK3359609)+ dostarlimab) - Participants will receive feladilimab (GSK3359609) administered continuously in combination with dostarlimab.

Experimental: Part 2A: Dose escalation (feladilimab (GSK3359609)+dostarlimab+cobolimab) - Participants will receive feladilimab (GSK3359609) administered continuously in combination with dostarlimab followed by cobolimab.

Experimental: Part 2A: Dose escalation (feladilimab (GSK3359609)+bintrafusp alfa) - Participants will receive feladilimab (GSK3359609) administered continuously in combination with bintrafusp alfa.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parts 1 and 2: Number of participants with any months adverse event(s) (AE) and serious adverse event(s) (SAE)
Timepoint [1] 0 0
Up to 27 months
Primary outcome [2] 0 0
Parts 1 and 2: Number of participants with dose limiting toxicity (DLT)
Timepoint [2] 0 0
Up to 28 days
Primary outcome [3] 0 0
Parts 1 and 2: Number of participants with clinically significant changes in laboratory parameters and vital signs
Timepoint [3] 0 0
Up to 24 months
Primary outcome [4] 0 0
Parts 1 and 2: Number of participants requiring dose modifications
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Parts 1 and 2: Disease control rate (DCR)
Timepoint [1] 0 0
Up to 27 months
Secondary outcome [2] 0 0
Parts 1 and 2: Overall survival (OS)
Timepoint [2] 0 0
Up to 4 years
Secondary outcome [3] 0 0
Parts 1 and 2: Progression-free survival (PFS)
Timepoint [3] 0 0
Up to 27 months
Secondary outcome [4] 0 0
Parts 1 and 2: Time to overall response (TTR)
Timepoint [4] 0 0
Up to 27 months
Secondary outcome [5] 0 0
Parts 1 and 2: Duration of response (DOR)
Timepoint [5] 0 0
Up to 27 months
Secondary outcome [6] 0 0
Parts 1 and 2: Overall response rate (ORR)
Timepoint [6] 0 0
Up to 27 months
Secondary outcome [7] 0 0
Parts 1 and 2: Maximum observed plasma concentration (Cmax) and minimum observed plasma concentration (Cmin) of GSK3359609
Timepoint [7] 0 0
Up to 27 months
Secondary outcome [8] 0 0
Parts 1 and 2: Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK3359609 in plasma
Timepoint [8] 0 0
Up to 27 months
Secondary outcome [9] 0 0
Parts 1 and 2: Number of participants with positive results in Anti-drug antibody (ADA) test by GSK3359609 dose level
Timepoint [9] 0 0
Up to 27 months
Secondary outcome [10] 0 0
Part 1 and 2: Number of participants with positive results in GSK3359609
Timepoint [10] 0 0
Up to 27 months
Secondary outcome [11] 0 0
Part 2: Number of participants with DLT following administration of GSK3359609 in combination with chemotherapies
Timepoint [11] 0 0
Up to 28 days
Secondary outcome [12] 0 0
Part 2: Cmax and Cmin of GSK3174998
Timepoint [12] 0 0
Up to 24 months
Secondary outcome [13] 0 0
Part 2: AUC(0-tau) of GSK3174998
Timepoint [13] 0 0
Up to 24months
Secondary outcome [14] 0 0
Part 2: Cmax and Cmin of Pembrolizumab
Timepoint [14] 0 0
Up to 27 months
Secondary outcome [15] 0 0
Part 2: AUC(0-tau) of Pembrolizumab
Timepoint [15] 0 0
Up to 27 months
Secondary outcome [16] 0 0
Part 2: Number of participants with positive results in ADA test by GSK3359609 in combination with pembrolizumab or GSK3174998 dose level
Timepoint [16] 0 0
Up to 27 months
Secondary outcome [17] 0 0
Part 2: Number of participants with positive results in Pembrolizumab
Timepoint [17] 0 0
Up to 27 months
Secondary outcome [18] 0 0
Part 2: Number of participants with positive results in GSK3174998
Timepoint [18] 0 0
Up to 27 months
Secondary outcome [19] 0 0
Part 2: Cmax and Cmin of GSK3359609 combination with chemotherapies
Timepoint [19] 0 0
Up to 27 months
Secondary outcome [20] 0 0
Part 2: Number of participants with positive results in ADA test by GSK3359609 combination with chemotherapies dose level
Timepoint [20] 0 0
Up to 27 months
Secondary outcome [21] 0 0
Part 2: Cmax and Cmin of dostarlimab
Timepoint [21] 0 0
Up to 27 months
Secondary outcome [22] 0 0
Part 2: AUC(0-tau) of dostarlimab
Timepoint [22] 0 0
Up to 27 months
Secondary outcome [23] 0 0
Part 2: Cmax and Cmin of cobolimab
Timepoint [23] 0 0
Up to 27 months
Secondary outcome [24] 0 0
Part 2: AUC(0-tau) of cobolimab
Timepoint [24] 0 0
Up to 27 months
Secondary outcome [25] 0 0
Part 2: Cmax and Cmin of bintrafusp alfa
Timepoint [25] 0 0
Up to 27 months
Secondary outcome [26] 0 0
Part 2: AUC(0-tau) of bintrafusp alfa
Timepoint [26] 0 0
Up to 27 months

Eligibility
Key inclusion 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 malignancy that was diagnosed as locally advanced/metastatic or relapsed/refractory and is of one of the following tumor types: bladder/urothelial cancer of the upper and lower urinary tract; cervical; colorectal (includes appendix); esophagus, squamous cell; head and neck carcinoma; melanoma; malignant pleural mesothelioma (MPM); non-small-cell lung cancer (NSCLC), prostate; Microsatellite Instability-High/deficient mismatch repair (MSI-H/dMMR) tumor (Part 1B and Part 2B) and Human Papilloma Virus (HPV)-positive or Epstein-Barr (EBV)-positive tumor (Part 1B and Part 2B).
* 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; exceptions are in these tumor types in which pembrolizumab single agent may be a standard: NSCLC, head and neck squamous cell cancer (HNSCC), bladder/urothelial cancer, MSI-H/dMMR cancers and melanoma and cervical cancer. In Part 2B pembrolizumab combination expansion cohorts, prior treatment with anti-Programmed cell death protein 1(PD-1)/ Ligand-1 (L1) may not be required. 1) Participants must not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. 2) Participants who received prior PD-1/L1 therapy must fulfill the following requirements (Part 1B [except PK/PD cohort]/ Part 2B):a) Have achieved a CR, PR or SD and subsequently had disease progression while still on PD-1/L1 therapy; b) Have received at least 2 doses of an approved PD-1/L1 inhibitor (by any regulatory authority), c) Have demonstrated disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 within 18 weeks from the last dose of the PD-1/L1 inhibitor. The initial evidence of disease progression is to be confirmed by a second assessment no less than four weeks from the date of the first documented Progressive Disease (PD) (the confirmatory scan could be the Baseline eligibility scan for this study). 3) In Part 2A 5-fluorouracil (FU)/platinum combination with GSK3359609 and pembrolizumab cohort, participants must not have received prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy given as part of multimodal treatment for locally advanced disease).
* Archival tumor tissue obtained at any time from the initial diagnosis to study entry; a fresh tumor biopsy using a procedure that is safe for the participant on a lesion not previously irradiated unless lesion progressed 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 pharmacokinetic (PK) / pharmacodynamics (PD), dose randomized HNSCC, Melanoma dose expansion and Biomarker cohorts..
* Measurable disease per 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 unless agreed upon by GlaxoSmithKline (GSK).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
* Life expectancy of at least 12 weeks.
* Adequate organ function.
* QT interval corrected for heart rate according to Fridericia's formula (QTcF) <450 milliseconds (msec) or QTcF <480 msec for participants with bundle branch block.
* A female participant 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), and not lactating or 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 participants 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.
* Documented HPV/ EBV-positive tumor as determined by a local laboratory for Part 1B and Part 2B pembrolizumab combination viral-positive expansion cohorts only.
* Documented MSI-H or dMMR-positive tumor as determined by local laboratory for Part 1B and Part 2B pembrolizumab combination MSI-H/dMMR expansion cohorts only.
* ICOS expression result using an analytically validated immunohistochemistry (IHC) assay by central laboratory for Part 1B biomarker cohort only.
* Gene expression (GEX) result using an analytically validated method by central laboratory (Part 1B Biomarker Cohort only).
* PD-L1 combined positive score (CPS) <1 using the Food and Drug Administration (FDA) approved PD-L1 IHC 22C3 pharmdx assay by central laboratory testing for Part 2B HNSCC PD-L1 CPS <1 Cohort. Documented test result from FDA approved PD-L1 IHC 22C3 pharmDx assay in local laboratory, if available, may be accepted in lieu of the central laboratory test result.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Prior treatment with the following therapies:

* 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.
* Part 2B (GSK3359609/pembrolizumab combination): prior pembrolizumab washout is not required.
* 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 within the last two years except: Any other invasive malignancy for which the participant was definitively treated, has been disease-free for <=2 years and in the opinion of the principal investigator and GSK Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical trial; and curatively treated non-melanoma skin cancer.
* Central nervous system (CNS) metastases, with the following exception: • Participants 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. Participants with carcinomatous meningitis or leptomeningeal spread 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. Participants 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). 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 participant is on a stable dose.
* Condition requiring treatment with strong inhibitors/inducers of cytochrome p (CYP) 450 3A4 within 7 days prior to first dose of chemotherapy (requirement applies to participants enrolled to Part 2 chemotherapy combination with docetaxel).
* Active infection requiring systemic therapy, known human immunodeficiency virus infection, or positive test for hepatitis B active infection or hepatitis C active infection.
* 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 that required surgery.
* Receipt of any live vaccine within 4 weeks prior to first dose of study treatment.
* Recent history of allergen desensitization therapy within 4 weeks of starting study treatment.
* History of severe hypersensitivity to monoclonal antibodies or to the chemotherapies under investigation including any ingredient used in the formulation.
* 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 participant's safety, obtaining informed consent, or compliance to the study procedures.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/07/2023
Sample size
Target
Accrual to date
Final
829
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [2] 0 0
GSK Investigational Site - Melbourne
Recruitment hospital [3] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Oklahoma
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
China
State/province [8] 0 0
Shnghai
Country [9] 0 0
France
State/province [9] 0 0
Bordeaux Cedex
Country [10] 0 0
France
State/province [10] 0 0
Lyon cedex 08
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
France
State/province [12] 0 0
Villejuif cedex
Country [13] 0 0
Italy
State/province [13] 0 0
Toscana
Country [14] 0 0
Japan
State/province [14] 0 0
Chiba
Country [15] 0 0
Japan
State/province [15] 0 0
Osaka
Country [16] 0 0
Japan
State/province [16] 0 0
Tokyo
Country [17] 0 0
Netherlands
State/province [17] 0 0
Amsterdam
Country [18] 0 0
Spain
State/province [18] 0 0
Barcelona
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Spain
State/province [20] 0 0
Málaga
Country [21] 0 0
Spain
State/province [21] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Available to whom?
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02723955

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
WA,VIC
Funding & Sponsors
Primary sponsor
Commercial sector/Industry
Primary sponsor name
GlaxoSmithKline
Primary sponsor address
Primary sponsor country
Ethics approval
Ethics application status
Approved
 
Public notes
Investigators:
Michael Millward, Sir Charles Gairdner Hospital, Western Australia, Nedlands, Australia, 6009
Hui Gan, Austin Health, Victoria, Heidelberg, Australia, 3084
Danny Rischin, Peter MacCallum Cancer Institute, Victoria, Melbourne, Australia, 3000

Contacts
Principal investigator
Title 73 0
Name 73 0
Address 73 0
Country 73 0
Phone 73 0
Fax 73 0
Email 73 0
Contact person for public queries
Title 74 0
Name 74 0
Address 74 0
Country 74 0
Phone 74 0
Fax 74 0
Email 74 0
[email protected]
Contact person for scientific queries
Title 75 0
Name 75 0
Address 75 0
Country 75 0
Phone 75 0
Fax 75 0
Email 75 0
[email protected]