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

NCT02723955 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2046912016-000148-32
• Study Type: interventional
• Target: 829
• Locations: 9 countries
• Sites: 28

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

Outcome Measures

Primary Outcomes (16)

• Part 1A: Number of Participants With Any Adverse Event(s) (AEs) and Serious Adverse Event(s) (SAEs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. A summary of number of participants with any AEs and SAEs is presented. AEs were coded using the Medical Dictionary for Regulatory Affairs (MedDRA dictionary).

  Up to approximately 367 weeks

• Part 1A: Number of Participants With Dose Limiting Toxicity (DLT)

  DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 28-day DLT period and meets at least one of the DLT criteria: Febrile neutropenia; Grade 4 neutropenia of \>7 days in duration or requiring Granulocyte Colony-stimulating Factor (G-CSF), anemia, thrombocytopenia, non-hematologic toxicity; Grade 3 thrombocytopenia with bleeding, pneumonitis, toxicity that does not resolve to Grade 1 or baseline within 3 days; Grade 2 ocular toxicity; Toxicity that results in permanent discontinuation of feladilimab during the first four weeks of treatment; any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT.

  Up to 28 days

• Part 1A: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters

  Blood samples were collected for analysis of clinical chemistry parameters. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 0: None; G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only grade change data is presented for Baseline (B) and Worst-Case Post-Baseline (WCPB) as G0, G1, G2, G3, G4, and missing (M) here as "Parameter name, B GX, WCPB GX" where X=grade digit.

  Baseline (Day 1) and up to approximately 367 weeks

• Part 1A: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

  Normal ranges were 0.1 to 0.3 micromoles (umol)/liter (L) (direct bilirubin); 6 to 8.3 grams/L (protein); 100 to 250 international units (IU)/L (Lactate Dehydrogenase(LDH)); 2.3 - 4.1 picomoles/L (Free Triiodothyronine(T3)); 4.6 to 11.2 picomoles/L (Free Thyroxine(T4)); 0 and 0.04 microgram (ug)/L (Troponin I); 0 - 0.01 ug/L (Troponin T); 0.45 to 4.5 milliunits (Mu)/L (Thyrotropin(TSH)); and 6 to 24 millimoles/L (Urea). Participants were counted in worst case category that their value changes to low, normal or no change \[NC\] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.

  Up to approximately 367 weeks

• Part 1A: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters

  Blood samples were collected for analysis of hematology parameters. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 0: None; G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only grade change data is presented for Baseline (B) and Worst-Case Post-Baseline (WCPB) as G0, G1, G2, G3, G4, and missing (M) here as "Parameter name, B GX, WCPB GX" where X=grade digit.

  Baseline (Day 1) and up to approximately 367 weeks

• Part 1A: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

  Normal ranges were 0.01 to 0.3\*10\^9 cells/L (basophils), 0 to 500 cells /L (eosinophils), 41 to 50 percentage of red blood cells (RBC) in blood (hematocrit), 1,000 - 4,800 lymphocytes per microliter (µL) of blood (lymphocytes), 80-100 femtoliters (fl) (erythrocytes, mean corpuscular volume), 2 to 8 percentage of WBC (monocytes), 40 to 60 cells/mcL (neutrophils) and Women: 4.2 to 5.4 million RBC/ microliter (mcL) of blood and Men: 4.7 to 6.1 million RBC/ mcL (erythrocytes count). Participants were counted in worst case category that their value changes to low, normal or no change \[NC\] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.

  Up to approximately 367 weeks

• Part 1A: Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline

  Urine samples were collected to assess urine glucose, ketones and occult blood using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline (Day 1) was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase.

  Up to approximately 367 weeks

• Part 1A: Number of Participants With Dose Modifications of Feladilimab

  Number of participants with dose modifications (including dose delays, dose escalations and infusion interruptions) were reported for Feladilimab.

  Up to approximately 367 weeks

• Part 2A: Number of Participants With Any Adverse Event(s) (AEs) and Serious Adverse Event(s) (SAEs)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent disability/incapacity or Is a congenital anomaly/birth defect, Other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. A summary of number of participants with any AEs and SAEs is presented. AEs were coded using the MedDRA dictionary.

  Up to approximately 367 weeks

• Part 2A: Number of Participants With Dose Limiting Toxicity (DLT)

  DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 28-day DLT period and meets at least one of the DLT criteria: Febrile neutropenia; Grade 4 neutropenia of \>7 days in duration or requiring Granulocyte Colony-stimulating Factor (G-CSF), anemia, thrombocytopenia, non-hematologic toxicity; Grade 3 thrombocytopenia with bleeding, pneumonitis, toxicity that does not resolve to Grade 1 or baseline within 3 days; Grade 2 ocular toxicity; Toxicity that results in permanent discontinuation of feladilimab monotherapy or in combination during the first four weeks of treatment; any other event which in the judgment of the investigator and GSK Medical Monitor is considered to be a DLT.

  Up to 28 days

• Part 2A: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters

  Blood samples were collected for analysis of clinical chemistry parameters. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 0: None; G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only grade change data is presented for Baseline (B) and Worst-Case Post-Baseline (WCPB) as G0, G1, G2, G3, G4, and missing (M) here as "Parameter name, B GX, WCPB GX" where X=grade digit.

  Baseline (Day 1) and up to approximately 367 weeks

• Part 2A: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

  Normal ranges were 6 to 8.3 grams/L (protein); 100 to 250 international units (IU)/L (Lactate Dehydrogenase(LDH)); 2.3 - 4.1 picomoles/L (Free Triiodothyronine(T3)); 4.6 to 11.2 picomoles/L (Free Thyroxine(T4)); 0 and 0.04 microgram (ug)/L (Troponin I); 0 - 0.01 ug/L (Troponin T); 0.45 to 4.5 milliunits (Mu)/L (Thyrotropin(TSH)); and 6 to 24 millimoles/L (Urea). Participants were counted in worst case category that their value changes to low, normal or no change \[NC\] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.

  Up to approximately 367 weeks

• Part 2A: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters

  Blood samples were collected for analysis of hematology parameters. Laboratory parameters were graded according to CTCAE v4.03. Grade (G) 0: None; G1: mild; G2: moderate; G3: severe or medically significant; G4: life-threatening consequences. Higher grade indicates greater severity and increase in grade was defined relative to Baseline grade. Baseline (Day 1) was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Only grade change data is presented for Baseline (B) and Worst-Case Post-Baseline (WCPB) as G0, G1, G2, G3, G4, and missing (M) here as "Parameter name, B GX, WCPB GX" where X=grade digit.

  Baseline (Day 1) and up to approximately 367 weeks

• Part 2A: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

  Normal ranges were 0.01 to 0.3\*10\^9 cells/L (basophils), 0 to 500 cells /L (eosinophils), 41 to 50 percentage of RBC in blood (hematocrit), 2 to 8 percentage of WBC (monocytes), 40 to 60 cells/mcL (neutrophils) and Women: 4.2 to 5.4 million RBC/mcL of blood and Men: 4.7 to 6.1 million RBC/ mcL (erythrocytes count). Participants were counted in worst case category that their value changes to low, normal or no change \[NC\] or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g. High to High) or whose value became normal, were recorded in "To Normal or No Change" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.

  Up to approximately 367 weeks

• Part 2A: Number of Participants With Worst Case Urinalysis Results Post-Baseline Relative to Baseline

  Urine samples were collected to assess urine glucose, ketones and occult blood using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline (Day 1) was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase.

  Up to approximately 367 weeks

• Part 2A: Number of Participants With Dose Modifications of Feladilimab

  Number of participants with dose modifications (including dose delays, dose escalations, and infusion interruptions) were reported for Feladilimab

  Up to approximately 367 weeks

Secondary Outcomes (64)

• Part 1B: Number of Participants With Any Adverse Event(s) (AEs) and Serious Adverse Event(s) (SAEs)

  Up to approximately 367 weeks

• Part 1B: Number of Participants With Worst-case Grade Change From Baseline in Clinical Chemistry Parameters

  Baseline (Day 1) and up to approximately 367 weeks

• Part 1B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

  Up to approximately 367 weeks

• Part 1B: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters

  Baseline (Day 1) and up to approximately 367 weeks

• Part 1B: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

  Up to approximately 367 weeks

Study Arms (9)

Part 1A: Dose escalation feladilimab (GSK3359609)

EXPERIMENTAL

Participants will receive feladilimab (GSK3359609) administered continuously at a dose level dependent on to which dose level the participant is accrued.

Drug: feladilimab (GSK3359609)

Part 1B: Expansion feladilimab (GSK3359609)

EXPERIMENTAL

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

Drug: feladilimab (GSK3359609)

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

EXPERIMENTAL

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

Drug: feladilimab (GSK3359609); Drug: Pembrolizumab

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

EXPERIMENTAL

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

Drug: feladilimab (GSK3359609); Drug: GSK3174998

Part 2A: Safety run-in (feladilimab (GSK3359609)+chemotherapy)

EXPERIMENTAL

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.

Drug: feladilimab (GSK3359609); Drug: Docetaxel; Drug: Pemetrexed; Drug: Paclitaxel plus Carboplatin; Drug: Gemcitabine plus Carboplatin; Drug: Fluorouracil (5-FU) plus carboplatin or cisplatin

Part 2B: Expansion-feladilimab (GSK3359609)

EXPERIMENTAL

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

Drug: feladilimab (GSK3359609); Drug: Pembrolizumab

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

EXPERIMENTAL

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

Drug: feladilimab (GSK3359609); Drug: Dostarlimab

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

EXPERIMENTAL

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

Drug: feladilimab (GSK3359609); Drug: Dostarlimab; Drug: Cobolimab

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

EXPERIMENTAL

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

Drug: feladilimab (GSK3359609); Drug: Bintrafusp alfa

Interventions

feladilimab (GSK3359609) DRUG

Part 1A: Dose escalation feladilimab (GSK3359609); Part 1B: Expansion feladilimab (GSK3359609); Part 2A: Dose escalation (feladilimab (GSK3359609)+ dostarlimab); Part 2A: Dose escalation (feladilimab (GSK3359609)+GSK3174998); Part 2A: Dose escalation (feladilimab (GSK3359609)+bintrafusp alfa); Part 2A: Dose escalation (feladilimab (GSK3359609)+dostarlimab+cobolimab); Part 2A: Dose escalation (feladilimab (GSK3359609)+pembrolizumab); Part 2A: Safety run-in (feladilimab (GSK3359609)+chemotherapy); Part 2B: Expansion-feladilimab (GSK3359609)

GSK3174998 DRUG

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

Pembrolizumab DRUG

Part 2A: Dose escalation (feladilimab (GSK3359609)+pembrolizumab); Part 2B: Expansion-feladilimab (GSK3359609)

Docetaxel DRUG

Part 2A: Safety run-in (feladilimab (GSK3359609)+chemotherapy)

Pemetrexed DRUG

Part 2A: Safety run-in (feladilimab (GSK3359609)+chemotherapy)

Paclitaxel plus Carboplatin DRUG

Part 2A: Safety run-in (feladilimab (GSK3359609)+chemotherapy)

Gemcitabine plus Carboplatin DRUG

Part 2A: Safety run-in (feladilimab (GSK3359609)+chemotherapy)

Fluorouracil (5-FU) plus carboplatin or cisplatin DRUG

Part 2A: Safety run-in (feladilimab (GSK3359609)+chemotherapy)

Dostarlimab DRUG

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

Cobolimab DRUG

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

Bintrafusp alfa DRUG

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

Eligibility Criteria

• Age: 18 Years - 93 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (28)

GSK Investigational Site

Duarte, California, 91010, United States

Location

GSK Investigational Site

Los Angeles, California, 90025, United States

Location

GSK Investigational Site

Sarasota, Florida, 34232, United States

Location

GSK Investigational Site

New York, New York, 10016, United States

Location

GSK Investigational Site

New York, New York, 10032, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73104, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37232-6307, United States

Location

GSK Investigational Site

Heidelberg, Victoria, 3084, Australia

Location

GSK Investigational Site

Melbourne, Victoria, 3000, Australia

Location

GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Shnghai, 200126, China

Location

GSK Investigational Site

Bordeaux, 33076, France

Location

GSK Investigational Site

Lyon, 69373, France

Location

GSK Investigational Site

Paris, 75005, France

Location

GSK Investigational Site

Villejuif, 94805, France

Location

GSK Investigational Site

Siena, Tuscany, 53100, Italy

Location

GSK Investigational Site

Chiba, 277-8577, Japan

Location

GSK Investigational Site

Osaka, 589-8511, Japan

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Mága, 29010, Spain

Location

GSK Investigational Site

Seville, 41009, Spain

Location

Related Publications (2)

• 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.

  PMID: 36642813 BACKGROUND

• 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.

  PMID: 37593752 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab; Docetaxel; Pemetrexed; Paclitaxel; Carboplatin; Gemcitabine; Fluorouracil; Cisplatin; dostarlimab; bintrafusp alfa protein, human

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Uracil; Pyrimidinones; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2016
• First Posted: March 31, 2016
• Study Start: June 23, 2016
• Primary Completion: July 5, 2023
• Study Completion: July 5, 2023
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 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.
• Access Criteria: 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.

Locations

ES (5); CA (1); AU (3); IT (1); US (9); CN (1); FR (4); JP (3); NL (1)