Dose Escalation and Expansion Study of GSK3359609 in Participants With Selected Advanced Solid Tumors (INDUCE-1)

NCT ID: NCT02723955

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 829 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-23
• Study Completion Date: 2023-07-05

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 chemotherapy or pembrolizumab plus chemotherapy or dostarlimab plus cobolimab or Bintrafusp alfa combination dose escalation phase and Part 2B expansion phase with pembrolizumab. 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.

Conditions

Neoplasms

Keywords

ICOS receptor agonist antibody; Pembrolizumab; KEYNOTE-478; GSK3359609; Cohort expansion; Dose escalation; Dostarlimab; Cobolimab; Bintrafusp alfa

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

feladilimab (GSK3359609)

Intervention Type: DRUG

Part 1B: Expansion feladilimab (GSK3359609)

Participants will receive feladilimab (GSK3359609) administered continuously at a dose level chosen for further exploration in dose expansion cohorts.

Group Type: EXPERIMENTAL

feladilimab (GSK3359609)

Intervention Type: DRUG

Part 2A: Dose escalation (feladilimab (GSK3359609)+pembrolizumab)

Participants will receive feladilimab (GSK3359609) administered continuously in combination with pembrolizumab.

Group Type: EXPERIMENTAL

feladilimab (GSK3359609)

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Part 2A: Dose escalation (feladilimab (GSK3359609)+GSK3174998)

Participants will receive feladilimab (GSK3359609) administered continuously in combination with GSK3174998.

Group Type: EXPERIMENTAL

feladilimab (GSK3359609)

Intervention Type: DRUG

GSK3174998

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

feladilimab (GSK3359609)

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Pemetrexed

Intervention Type: DRUG

Paclitaxel plus Carboplatin

Intervention Type: DRUG

Gemcitabine plus Carboplatin

Intervention Type: DRUG

Fluorouracil (5-FU) plus carboplatin or cisplatin

Intervention Type: DRUG

Part 2B: Expansion-feladilimab (GSK3359609)

Participants will receive feladilimab (GSK3359609) administered continuously in combination with pembrolizumab.

Group Type: EXPERIMENTAL

feladilimab (GSK3359609)

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Part 2A: Dose escalation (feladilimab (GSK3359609)+ dostarlimab)

Participants will receive feladilimab (GSK3359609) administered continuously in combination with dostarlimab.

Group Type: EXPERIMENTAL

feladilimab (GSK3359609)

Intervention Type: DRUG

Dostarlimab

Intervention Type: DRUG

Part 2A: Dose escalation (feladilimab (GSK3359609)+dostarlimab+cobolimab)

Participants will receive feladilimab (GSK3359609) administered continuously in combination with dostarlimab followed by cobolimab.

Group Type: EXPERIMENTAL

feladilimab (GSK3359609)

Intervention Type: DRUG

Dostarlimab

Intervention Type: DRUG

Cobolimab

Intervention Type: DRUG

Part 2A: Dose escalation (feladilimab (GSK3359609)+bintrafusp alfa)

Participants will receive feladilimab (GSK3359609) administered continuously in combination with bintrafusp alfa.

Group Type: EXPERIMENTAL

feladilimab (GSK3359609)

Intervention Type: DRUG

Bintrafusp alfa

Intervention Type: DRUG

Interventions

feladilimab (GSK3359609)

Intervention Type: DRUG

GSK3174998

Intervention Type: DRUG

Pembrolizumab

Intervention Type: DRUG

Docetaxel

Intervention Type: DRUG

Pemetrexed

Intervention Type: DRUG

Paclitaxel plus Carboplatin

Intervention Type: DRUG

Gemcitabine plus Carboplatin

Intervention Type: DRUG

Fluorouracil (5-FU) plus carboplatin or cisplatin

Intervention Type: DRUG

Dostarlimab

Intervention Type: DRUG

Cobolimab

Intervention Type: DRUG

Bintrafusp alfa

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Capable of giving signed, written informed consent.
• Male or female, age 18 to 93 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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 93 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Duarte, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Sarasota, Florida, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Oklahoma City, Oklahoma, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Nashville, Tennessee, United States

GSK Investigational Site

Nashville, Tennessee, United States

GSK Investigational Site

Heidelberg, Victoria, Australia

GSK Investigational Site

Melbourne, Victoria, Australia

GSK Investigational Site

Nedlands, Western Australia, Australia

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Shnghai, , China

GSK Investigational Site

Bordeaux, , France

GSK Investigational Site

Lyon, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Villejuif, , France

GSK Investigational Site

Siena, Tuscany, Italy

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Mága, , Spain

GSK Investigational Site

Seville, , Spain

Countries

United States; Australia; Canada; China; France; Italy; Japan; Netherlands; Spain

References

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.

Reference Type: BACKGROUND

PMID: 36642813 (View on PubMed)

Yadavilli S, Waight JD, Brett S, Bi M, Zhang T, Liu YB, Ellis C, Turner DC, Hahn A, Shi H, Seestaller-Wehr L, Jing J, Xie Q, Shaik JS, Ji X, Gagnon R, Fieles W, Hook L, Grant S, Hopley S, DeYoung MP, Blackwell C, Chisamore M, Biddlecombe R, Figueroa DJ, Hopson CB, Srinivasan R, Smothers J, Maio M, Rischin D, Olive D, Paul E, Mayes PA, Hoos A, Ballas M. Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint Blockade. Cancer Res Commun. 2023 Aug 16;3(8):1564-1579. doi: 10.1158/2767-9764.CRC-22-0293. eCollection 2023 Aug.

Reference Type: DERIVED

PMID: 37593752 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000148-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

204691

Identifier Type: -

Identifier Source: org_study_id