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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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

Date last updated

21/02/2024

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]

2016-000148-32

Secondary ID [2]

204691

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Neoplasms

Condition category

Condition code

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - feladilimab (GSK3359609)
Treatment: Drugs - GSK3174998
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Docetaxel
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Paclitaxel plus Carboplatin
Treatment: Drugs - Gemcitabine plus Carboplatin
Treatment: Drugs - Fluorouracil (5-FU) plus carboplatin or cisplatin
Treatment: Drugs - Dostarlimab
Treatment: Drugs - Cobolimab
Treatment: Drugs - Bintrafusp alfa

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.

Treatment: Drugs: feladilimab (GSK3359609)

Treatment: Drugs: GSK3174998

Treatment: Drugs: Pembrolizumab

Treatment: Drugs: Docetaxel

Treatment: Drugs: Pemetrexed

Treatment: Drugs: Paclitaxel plus Carboplatin

Treatment: Drugs: Gemcitabine plus Carboplatin

Treatment: Drugs: Fluorouracil (5-FU) plus carboplatin or cisplatin

Treatment: Drugs: Dostarlimab

Treatment: Drugs: Cobolimab

Treatment: Drugs: Bintrafusp alfa

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Parts 1 and 2: Number of participants with any months adverse event(s) (AE) and serious adverse event(s) (SAE)

Timepoint [1]

Up to 27 months

Primary outcome [2]

Parts 1 and 2: Number of participants with dose limiting toxicity (DLT)

Timepoint [2]

Up to 28 days

Primary outcome [3]

Parts 1 and 2: Number of participants with clinically significant changes in laboratory parameters and vital signs

Timepoint [3]

Up to 24 months

Primary outcome [4]

Parts 1 and 2: Number of participants requiring dose modifications

Timepoint [4]

Up to 24 months

Secondary outcome [1]

Parts 1 and 2: Disease control rate (DCR)

Timepoint [1]

Up to 27 months

Secondary outcome [2]

Parts 1 and 2: Overall survival (OS)

Timepoint [2]

Up to 4 years

Secondary outcome [3]

Parts 1 and 2: Progression-free survival (PFS)

Timepoint [3]

Up to 27 months

Secondary outcome [4]

Parts 1 and 2: Time to overall response (TTR)

Timepoint [4]

Up to 27 months

Secondary outcome [5]

Parts 1 and 2: Duration of response (DOR)

Timepoint [5]

Up to 27 months

Secondary outcome [6]

Parts 1 and 2: Overall response rate (ORR)

Timepoint [6]

Up to 27 months

Secondary outcome [7]

Parts 1 and 2: Maximum observed plasma concentration (Cmax) and minimum observed plasma concentration (Cmin) of GSK3359609

Timepoint [7]

Up to 27 months

Secondary outcome [8]

Parts 1 and 2: Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK3359609 in plasma

Timepoint [8]

Up to 27 months

Secondary outcome [9]

Parts 1 and 2: Number of participants with positive results in Anti-drug antibody (ADA) test by GSK3359609 dose level

Timepoint [9]

Up to 27 months

Secondary outcome [10]

Part 1 and 2: Number of participants with positive results in GSK3359609

Timepoint [10]

Up to 27 months

Secondary outcome [11]

Part 2: Number of participants with DLT following administration of GSK3359609 in combination with chemotherapies

Timepoint [11]

Up to 28 days

Secondary outcome [12]

Part 2: Cmax and Cmin of GSK3174998

Timepoint [12]

Up to 24 months

Secondary outcome [13]

Part 2: AUC(0-tau) of GSK3174998

Timepoint [13]

Up to 24months

Secondary outcome [14]

Part 2: Cmax and Cmin of Pembrolizumab

Timepoint [14]

Up to 27 months

Secondary outcome [15]

Part 2: AUC(0-tau) of Pembrolizumab

Timepoint [15]

Up to 27 months

Secondary outcome [16]

Part 2: Number of participants with positive results in ADA test by GSK3359609 in combination with pembrolizumab or GSK3174998 dose level

Timepoint [16]

Up to 27 months

Secondary outcome [17]

Part 2: Number of participants with positive results in Pembrolizumab

Timepoint [17]

Up to 27 months

Secondary outcome [18]

Part 2: Number of participants with positive results in GSK3174998

Timepoint [18]

Up to 27 months

Secondary outcome [19]

Part 2: Cmax and Cmin of GSK3359609 combination with chemotherapies

Timepoint [19]

Up to 27 months

Secondary outcome [20]

Part 2: Number of participants with positive results in ADA test by GSK3359609 combination with chemotherapies dose level

Timepoint [20]

Up to 27 months

Secondary outcome [21]

Part 2: Cmax and Cmin of dostarlimab

Timepoint [21]

Up to 27 months

Secondary outcome [22]

Part 2: AUC(0-tau) of dostarlimab

Timepoint [22]

Up to 27 months

Secondary outcome [23]

Part 2: Cmax and Cmin of cobolimab

Timepoint [23]

Up to 27 months

Secondary outcome [24]

Part 2: AUC(0-tau) of cobolimab

Timepoint [24]

Up to 27 months

Secondary outcome [25]

Part 2: Cmax and Cmin of bintrafusp alfa

Timepoint [25]

Up to 27 months

Secondary outcome [26]

Part 2: AUC(0-tau) of bintrafusp alfa

Timepoint [26]

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?

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]

GSK Investigational Site - Heidelberg

Recruitment hospital [2]

GSK Investigational Site - Melbourne

Recruitment hospital [3]

GSK Investigational Site - Nedlands

Recruitment postcode(s) [1]

3084 - Heidelberg

Recruitment postcode(s) [2]

3000 - Melbourne

Recruitment postcode(s) [3]

6009 - Nedlands

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

Florida

Country [3]

United States of America

State/province [3]

New York

Country [4]

United States of America

State/province [4]

Oklahoma

Country [5]

United States of America

State/province [5]

Pennsylvania

Country [6]

United States of America

State/province [6]

Tennessee

Country [7]

Canada

State/province [7]

Ontario

Country [8]

China

State/province [8]

Shnghai

Country [9]

France

State/province [9]

Bordeaux Cedex

Country [10]

France

State/province [10]

Lyon cedex 08

Country [11]

France

State/province [11]

Paris

Country [12]

France

State/province [12]

Villejuif cedex

Country [13]

Italy

State/province [13]

Toscana

Country [14]

Japan

State/province [14]

Chiba

Country [15]

Japan

State/province [15]

Osaka

Country [16]

Japan

State/province [16]

Tokyo

Country [17]

Netherlands

State/province [17]

Amsterdam

Country [18]

Spain

State/province [18]

Barcelona

Country [19]

Spain

State/province [19]

Madrid

Country [20]

Spain

State/province [20]

Málaga

Country [21]

Spain

State/province [21]

Sevilla

Funding & Sponsors

Primary sponsor type

Commercial sector/Industry

Name

GlaxoSmithKline

Address

Country

Other collaborator category [1]

Commercial sector/Industry

Name [1]

Merck Sharp & Dohme LLC

Address [1]

Country [1]

Ethics approval

Ethics application status

Summary

Brief summary

GSK3359609 is an anti-Inducible T cell Co-Stimulator (ICOS) receptor agonist antibody
intended for the treatment of cancers of different histology. This is a first-time-in-human
(FTIH), open-label, multicenter study designed to investigate the safety, pharmacology, and
preliminary antitumor activity in participants with selected, advanced or recurrent solid
tumors with the aim to establish recommended dose(s) of GSK3359609 for further exploration as
monotherapy and in combination with pembrolizumab or chemotherapy regimens. The study is
comprised of two primary parts, each composed of two phases: Part 1: GSK3359609 monotherapy
with Part 1A as dose escalation phase and Part 1B as cohort expansion phase; Part 2:
GSK3359609 combination therapy with Part 2A pembrolizumab or GSK3174998 or dostarlimab or
dostarlimab plus cobolimab or Bintrafusp alfa combination dose escalation phase and Part 2B
expansion phase with pembrolizumab. Part 2A GSK3359609 combinations with chemotherapy will
only consist of safety run-in cohorts. Each part and phase of the study includes a screening
period, a treatment period, and a follow-up period. The primary objective of the study is to
determine the safety, tolerability, maximum tolerated dose or the maximum administered dose
of GSK3359609 alone or in combination.

Trial website

https://clinicaltrials.gov/ct2/show/NCT02723955

Trial related presentations / publications

Turner DC, Wada R, Zhou H, Wang X, de Greef R, Valiathan C, Zhang L, Zhang N, Kuchimanchi M, Chen TT, Ballas M, Visser SAG. Model-based meta-analysis of non-small cell lung cancer with standard of care PD-1 inhibitors and chemotherapy for early development decision making. CPT Pharmacometrics Syst Pharmacol. 2023 Nov;12(11):1751-1763. doi: 10.1002/psp4.12917. Epub 2023 Jan 31.

Public notes

Contacts

Principal investigator

Name

GSK Clinical Trials

Address

GlaxoSmithKline

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

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

Name

Address

Country

Phone

Fax

Contact person for public queries

Title

Name

Address

Country

Phone

Fax

GSKClinicalSupportHD@gsk.com

Contact person for scientific queries

Title

Name

Address

Country

Phone

Fax

GSKClinicalSupportHD@gsk.com

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02723955