NeoplasmsPhase 1/2NCT03693612

GSK3359609 Plus Tremelimumab for the Treatment of Advanced Solid Tumors

A Phase 1/2 study testing feladilimab, Tremelimumab and Docetaxel in people with Neoplasms, run by GlaxoSmithKline at 8 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms
What is being tested?: feladilimab, Tremelimumab and Docetaxel
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 8 sitesin 3 countries
Study dates: 26 Nov 2018to 16 Sep 2021
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
Male or female, aged 18 years or older.
Body weight >=30 kilograms (kg).
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: a) Part 1: cutaneous melanoma; HNSCC (oral cavity, larynx, oropharynx, hypopharynx, nasal cavity/paranasal sinuses); non-small cell lung cancer (squamous and non-squamous); urothelial carcinoma of the upper and lower urinary tract; clear cell renal carcinoma; castrate resistant prostate adenocarcinoma. b) Part 2: HNSCC (oral cavity, larynx, pharynx, paranasal sinuses).
Part 1 only: 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, or where standard therapy is refused. May be anti-PD-1/anti-PD-L1 experienced or naïve.
Part 2 only: Disease that has progressed after receiving platinum-based chemotherapy (unless medically contraindicated or discontinued due to toxicity) and anti-PD-1/anti-PD-L1 therapy (in combination or as separate lines of therapy in either sequence).

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Measurable disease per RECIST version 1.1 guidelines. 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) score of 0 or 1.
Adequate organ function.
A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions apply: a) Not a woman of childbearing potential (WOCBP); or, b) A WOCBP who agrees to follow the contraceptive while receiving study intervention and for at least 180 days after the last dose of study intervention.
A male subject must agree to use a highly effective contraception while receiving study intervention and for at least 180 days after the last dose of study intervention and refrain from donating sperm during this period.
Agree to collection of tumor tissue: a) Part 1 and Part 2: Archival tumor tissue collected any time from the initial diagnosis of invasive malignancy; a fresh tumor biopsy will be required if archival specimen is unavailable prior to first dose. b) Part 1 pharmacokinetic/pharmacodynamic cohort(s): Archival tissue as noted in point (a) above. Paired tumor biopsies: tumor tissue collected any time after completion of dosing of the last therapy and prior to first dose and an on-treatment biopsy. c) Part 2: A minimum of 15 subjects from each arm will be required to provide paired tumor biopsies (in addition to the archival tissues as noted in point (a) above): tumor tissue collected any time after completion of dosing of the last therapy and prior to first dose and an on-treatment biopsy.

Who cannot join

Received prior treatment with the following therapies; calculation is based on date of last therapy to date of first dose of study intervention or SOC: a) Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4 [including tremelimumab] or Inducible T Cell Co-Stimulator (ICOS)-directed therapies at any time; b) >=4 lines of prior anticancer treatment: In subjects that relapse or progress within 1 year from the beginning of adjuvant or concurrent therapy, the adjuvant/concurrent therapy is considered first line therapy; c) Systemic anticancer therapy or investigational therapy within 30 days, or 5 half-lives, whichever is shorter; at least 14 days must have elapsed between the date of the last prior therapy to the date of first dose of study intervention or SOC.
Prior radiation therapy: permissible if at least one non-irradiated measurable lesion is available for assessment per RECIST v1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. At least 14 days must have elapsed between the date of the last dosage of radiation and the first dose of study intervention/SOC.
Invasive malignancy or history of invasive malignancy other than disease under study within the last two years, except: a) Any other invasive malignancy for which the subject was definitively treated, has been disease-free for <=2 years and in the opinion of the Investigator and Medical Monitor will not affect the evaluation of the effects of the study intervention or SOC on the currently targeted malignancy, may be included in this clinical study; Curatively treated non-melanoma skin cancer or successfully treated in-situ carcinoma.
Toxicity from previous anticancer treatment that includes: a) >=Grade 3 toxicity considered related to prior immunotherapy and that led to treatment discontinuation; b) Toxicity related to prior treatment that has not resolved to <=Grade 1 (except alopecia, vitiligo, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be <=Grade 2).
Central nervous system (CNS) metastases, with the following exception: Subjects with previously treated CNS metastases who are clinically stable and had no requirement for steroids during at least 14 days prior to first dose of study intervention or SOC.
Major surgery <=28 days of first dose of study intervention or SOC.

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Autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years. Replacement therapies which include physiological doses of corticosteroids for treatment of endocrinopathies (i.e., adrenal insufficiency) are not considered systemic treatments.
Recent history (within 24 weeks) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess.
Receiving systemic steroids (>=10 milligrams [mg] oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to first dose of study intervention or SOC.
Prior allogeneic/autologous bone marrow or solid organ transplantation.
Received live-virus vaccine within 30 days from start of study intervention or SOC.
Current or history of idiopathic pulmonary fibrosis, pneumonitis (for past, subject is excluded if steroids were required), interstitial lung disease or organizing pneumonia.
Recent history (within 24 weeks) of uncontrolled, symptomatic ascites, pleural or pericardial effusions.
History or evidence of cardiac abnormalities within the 24 weeks prior to enrollment which include: a) Serious uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third degree atrioventricular block. b) Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting. c) Symptomatic pericarditis.
Current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
Active infection requiring systemic therapy.
Known human immunodeficiency virus infection; positive test for hepatitis B active infection (presence of hepatitis B surface antigen) or hepatitis C active infection.
History of severe hypersensitivity to monoclonal antibodies, the Standard of Care agents, including any ingredient used in the formulation, based on which treatment the subject is to receive.
Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator.
For subjects receiving SOC: Requires therapy with a medication that may alter the PK of the SOC agent (e.g., strong inducers or inhibitors of cytochrome P (CYP)3A4 for subjects receiving docetaxel or paclitaxel) during the study treatment period. Please refer to the package insert for the agent the subject is to receive.
For subjects receiving SOC: Any contraindication, per the package insert and/or Institutional guidelines, to the treatment the subject is to receive.

Trial locations and contacts

8 sites in 3 countries.

Country

City, postcode or hospital

8 sites in 3 countries

United States5 sites

GSK Investigational Site
Boston, Massachusetts, 02215
GSK Investigational Site
New York, New York, 10016-4744
GSK Investigational Site
New York, New York, 10032
GSK Investigational Site
Pittsburgh, Pennsylvania, 15232
GSK Investigational Site
San Antonio, Texas, 78229

Other trials in United States

Canada2 sites

GSK Investigational Site
Ottawa, Ontario, K1H 8L6
GSK Investigational Site
Toronto, Ontario, M5G 2M9

Other trials in Canada

Australia1 site

GSK Investigational Site
Melbourne, Victoria, 3000

Other trials in Australia

About this study

Official title: A Phase I/II, Open-label, Two Part Study of GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors

The purpose of this study is to evaluate if the combination of GSK3359609 and tremelimumab is safe and tolerable (Part 1) and provides significant survival benefit to subjects with relapsed/refractory (R/R) Head and Neck Squamous Cell Carcinomas (HNSCC) to warrant further clinical investigation (Part 2). Part 1 (dose escalation) will enroll subjects with advanced, selected solid tumors. Subjects will receive escalating doses of GSK3359609 and tremelimumab in combination in Part 1. Part 2 is randomized expansion and will enroll subjects with R/R HNSCC who have disease progression after receiving at least 1 platinum-based chemotherapy and at least 1 anti-programmed death receptor protein-1 (PD-1)/anti-programmed death-ligand 1 (PD-L1) therapy, whether in combination or separately. In Part 2, subjects will be randomized in a ratio of 2:1 to receive either GSK3359609 in combination with tremelimumab at the recommended Phase 2 dose or investigators choice of a single-agent standard of care (SOC) therapy including paclitaxel, docetaxel or cetuximab. The total duration of subjects in the study will be approximately 4 years.

Conditions: Neoplasms
Being tested: feladilimab, Tremelimumab, Docetaxel, Paclitaxel, Cetuximab
Keywords: advanced solid tumor, Head and Neck Squamous Cell Carcinoma, standard of care, GSK3359609, urothelial carcinoma of the upper and lower urinary tract, non-small cell lung cancer, cutaneous melanoma, Tremelimumab, clear cell renal carcinoma, castrate resistant prostate adenocarcinoma
Medical subject headings: Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Melanoma, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

feladilimabDrug
feladilimab is humanized anti-ICOS agonist immunoglobulin G (IgG) 4 monoclonal antibody (mAb), which will be administered as an intravenous (IV) infusion once every 3 weeks.
TremelimumabDrug
Tremelimumab is humanized anti-CTLA-4 IgG2 mAb, which will be administered as an IV infusion once every 3 weeks for 6 doses, thereafter once every 12 weeks .
DocetaxelDrug
Docetaxel is a microtubule stabilizer which will be administered as an IV infusion once every 3 weeks at a dose of 75 milligrams per meter square (mg/m^2).
PaclitaxelDrug
Paclitaxel is a microtubule stabilizer which will be administered as an IV infusion once weekly at a dose of 80 mg/m^2.
CetuximabDrug
Cetuximab is a recombinant, human/mouse chimeric anti-estimated glomerular filtration rate (EGFR) mAb. Cetuximab will be administered at a loading dose of 400 mg/m^2 followed by 250 mg/m^2 once weekly.

Study groups in NCT03693612
Study group	Role	What they receive
Part 1: feladilimab +tremelimumab	Experimental	In Part 1, subjects with advanced selected solid tumors will be enrolled. Subjects will be administered escalating doses of feladilimab and tremelimumab in combination. feladilimab will be administered every 3 weeks and tremelimumab will be administered every 3 weeks for 6 doses and every 12 weeks thereafter. Receives: Drug: feladilimab; Drug: Tremelimumab
Part 2: feladilimab +tremelimumab	Experimental	In Part 2, subjects with R/R HNSCC who have disease progression after receiving at least one platinum-based chemotherapy and at least one anti-PD-1/PD-L1 will be enrolled. Subjects will be administered feladilimab in combination with tremelimumab at recommended Phase 2 dose as determined from Part 1. Receives: Drug: feladilimab; Drug: Tremelimumab
Part 2: SOC	Active comparator	In Part 2, subjects with R/R HNSCC who have disease progression after receiving at least one platinum-based chemotherapy and at least one anti-PD-1/PD-L1 will be enrolled. Subjects will be administered a single agent SOC therapy of either paclitaxel, docetaxel or cetuximab as per the investigators choice. Receives: Drug: Docetaxel; Drug: Paclitaxel; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1
A DLT is considered by the investigator to be clinically relevant, attributed event within first 28 days of intervention meeting the following criteria of toxicity, Hematologic: Febrile neutropenia, Grade 4 neutropenia of greater than (>) 7 days in duration or requiring Granulocyte- Colony stimulating factor (G-CSF), Grade 4 anemia and Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia; Non-hematologic: Grade 4 toxicity, Grade 3 pneumonitis, any greater than or equal to (≥) Grade 2 pneumonitis that does not resolve to less than or equal to (≤ ) Grade 1 within 3 days of the initiation of maximal supportive care, Grade 3 toxicity that does not resolve to Grade 1 or baseline within 3 days despite optimal supportive care and any Grade 2 ocular toxicity requiring systemic steroids, or any ≥ Grade 3 ocular toxicity.
Measured: Up to 28 days
Number of Participants With DLTs According to Severity-Part 1
The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for ≤24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE.
Measured: Up to 28 days
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)-Part 1
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An 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; is a congenital anomaly/birth defect and important medical events may jeopardize the subject or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before. AESIs are defined as events of potential immunologic etiology, including immune related AEs.
Measured: Up to 4 years
Number of Participant With AE/SAE/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1
The number of participants with AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.
Measured: Up to 4 years
Number of Participants With AEs, SAEs, AESIs According to Severity - Part 1
The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for ≤24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE.
Measured: Up to 4 years
Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1
The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.
Measured: Up to 4 years
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)-Part 1
SBP and DBP were measured after 5 minutes of rest for the participant.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Temperature-Part 1
Temperature was measured after 5 minutes of rest for the participant.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Pulse Rate-Part 1
Pulse rate was measured after 5 minutes of rest for the participant.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Respiratory Rate-Part 1
Respiratory rate was measured after 5 minutes of rest for the participant.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Oxygen Saturation-Part 1
Oxygen saturation was measured using pulse oximeter after 5 minutes of rest for the participant.
Measured: Baseline (Day 1) and Week 4
Number of Participants With Electrocardiogram (ECG) Findings
Single 12-lead ECG was obtained using an automated ECG machine. ECG findings were categorized as: normal, abnormal - clinically significant (CS), or abnormal - not clinically significant (NCS), as determined by the investigator.
Measured: Baseline (Pre dose, Day 1) and up to 4 Years
Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 1
Blood samples were collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet counts.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Hemoglobin Level-Part 1
Blood samples were collected to assess change from baseline in hemoglobin level.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Hematocrit Level-Part 1
Blood samples were collected to assess change from baseline in hematocrit level.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Erythrocytes Count-Part 1
Blood samples were collected to assess change from baseline in Erythrocytes count.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Albumin and Total Protein Levels-Part 1
Blood samples were collected to assess change from Baseline in albumin and total protein levels.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Creatinine and Bilirubin Levels-Part 1
Blood samples were collected to assess change from baseline in creatinine and bilirubin levels.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) Levels-Part 1
Blood samples were collected to assess change from baseline in ALT, AST ALP, LDH levels.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Amylase and Lipase Levels-Part 1
Blood samples were collected to assess change from baseline in amylase and lipase levels.
Measured: Baseline (Day 1) and week 4
Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels-Part 1
Blood samples were collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Specific Gravity of Urine-Part 1
Urine samples were collected to assess change from baseline in specific gravity of urine.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Potential of Hydrogen (pH) of Urine-Part 1
Urine samples were collected to assess change from baseline in pH of urine.
Measured: Baseline (Day 1) and Week 4
Number of Participants With Abnormal Urinalysis Parameters-Part 1
The dipstick test gives positive or negative results for protein, ketones, occult blood and glucose in urine. Positive test results were considered as abnormal. Number of participants with positive test results have been summarized.
Measured: Week 4
Change From Baseline in Thyroid Stimulating Hormone (TSH) or Thyrotropin-Part 1
Blood samples were collected to assess change from Baseline in TSH.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Free Triiodothyronine (T3)-Part 1
Blood samples were collected to assess change from Baseline in free T3.
Measured: Baseline (Day 1) and Week 4
Change From Baseline in Free Thyroxine (T4)-Part 1
Blood samples were collected to assess change from baseline in free T4.
Measured: Baseline (Day 1) and Week 4
Overall Survival-Part 2
For participants in Part 2, overall survival is defined as time from the date of randomization to the date of death due to any cause.
Measured: Up to 4 years

Secondary outcomes (47)

Overall Response Rate-Part 1
Overall response rate is defined as percentage of participants with confirmed complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 millimeter [mm]) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) at any time as per response evaluation criteria in solid tumors (RECIST) version 1.1.
Measured: Up to 4 years
Overall Response Rate-Part 2
Overall response rate is defined as percentage of participants with confirmed complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) at any time as per RECIST version 1.1.
Measured: Up to 4 years
Disease Control Rate-Part 1
Disease control rate is defined as percentage of subjects with confirmed complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) or at least 18 weeks of stable disease (Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) as per RECIST version 1.1.
Measured: Up to 4 years
Disease Control Rate-Part 2
Disease control rate is defined as percentage of subjects with confirmed complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) or at least 18 weeks of stable disease (Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) as per RECIST version 1.1.
Measured: Up to 4 years
Progression Free Survival-Part 2
For Part 2, progression free survival duration is defined as the time from the date of randomization to first documented evidence of disease progression (At least a 20% increase in the sum of diameters of target lesions and In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm) or death (regardless of cause of death), whichever comes first as per RECIST version 1.1.
Measured: Up to 4 years
Time to Response-Part 2
Time to response is defined as the time from the first dose to the first documented evidence of complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 mm) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) for participants with a confirmed CR or PR as per RECIST version 1.1.
Measured: Up to 4 years
Duration of Response-Part 2
Duration of response is defined as time from the first documented evidence of response until the first documented sign of disease progression or death among participants who achieve a response (CR [Disappearance of all target lesions. Any pathological lymph nodes {whether target or non-target} must have reduction in short axis to <10 mm or PR [At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters] as per RECIST version 1.1).
Measured: Up to 4 years
Maximum Observed Plasma Concentration (Cmax) of Feladilimab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose, end of infusion and 4 hours post dose at Day 1
Cmax of Tremelimumab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose, end of infusion and 4 hours post dose at Day 1
Cmax of Feladilimab-Part 2
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, 19, 25, then every 12 weeks for 2 years; end of infusion at Weeks 1, 19 and 25; and 4 hours post-infusion at Week 1
Cmax of Tremelimumab-Part 2
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, 19, 25, then every 12 weeks for 2 years; end of infusion at Weeks 1, 19 and 25; and 4 hours post-infusion at Week 1
Minimum Observed Plasma Concentration (Cmin) of Feladilimab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose, end of infusion and 4 hours post dose at Day 1
Cmin of Tremelimumab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose, end of infusion and 4 hours post dose at Day 1
Cmin of Feladilimab-Part 2
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, then every 12 weeks for 2 years; end of infusion; and 4 hours post-infusion at Week 1
Cmin of Tremelimumab-Part 2
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, then every 12 weeks for 2 years; end of infusion; and 4 hours post-infusion at Week 1
Area Under the Plasma Concentration-time Curve (AUC[0-t]) of Feladilimab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose, end of infusion and 4 hours post dose at Day 1
AUC(0-t) of Tremelimumab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose, end of infusion and 4 hours post dose at Day 1
AUC(0-t) of Feladilimab-Part 2
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment.
Measured: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, 19, 25, then every 12 weeks for 2 years; end of infusion at Weeks 1, 19 and 25, and 4 hours post-infusion at Week 1
AUC(0-t) of Tremelimumab-Part 2
Blood samples were planned to be collected at indicated time points for pharmacokinetic assessment
Measured: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, then every 12 weeks for 2 years; end of infusion; and 4 hours post-infusion at Week 1
Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 1
Serum samples were collected and tested for the presence of antibodies to feladilimab.
Measured: Pre-dose at Week 4, 7, 10 and 13
Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 1
Serum samples were collected and tested for the presence of antibodies to tremelimumab.
Measured: Pre-dose at Week 1, 4, 7, 10 and 13
Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 2
Serum samples will be collected and tested for the presence of antibodies to feladilimab.
Measured: Up to 2.5 years
Change From Baseline in Free T4-Part 2
Blood samples will be collected to assess change from baseline in free T4.
Measured: Baseline and up to 2 years
Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 2
Serum samples will be collected and tested for the presence of antibodies to tremelimumab.
Measured: Up to 2.5 years
Number of Participants With AEs, SAEs and AESI-Part 2
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An 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; is a congenital anomaly/birth defect and important medical events may jeopardize the subject or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before. AESIs are defined as events of potential immunologic etiology, including immune related AEs.
Measured: Up to 4 years
Number of Participants With AEs, SAEs, AESIs Based on Severity-Part 2
The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for ≤24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE
Measured: Up to 4 years
Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 2
The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were planned to be summarized.
Measured: Up to 4 years
Change From Baseline in SBP and DBP-Part 2
SBP and DBP will be measured after 5 minutes of rest for the participant.
Measured: Baseline and up to 2 years
Change From Baseline in Temperature-Part 2
Temperature will be measured after 5 minutes of rest for the participant.
Measured: Baseline and up to 2 years
Change From Baseline in Pulse Rate-Part 2
Pulse rate will be measured after 5 minutes of rest for the participant.
Measured: Baseline and up to 2 years
Change From Baseline in Respiratory Rate-Part 2
Respiratory rate will be measured after 5 minutes of rest for the participant.
Measured: Baseline and up to 2 years
Change From Baseline in Oxygen Saturation-Part 2
Oxygen saturation will be measured using pulse oximetry after 5 minutes of rest for the participant.
Measured: Baseline and up to 2 years
Change From Baseline in ECG Measurement-Part 2
Single 12-lead ECG will be obtained using an automated ECG machine.
Measured: Baseline (Pre-dose) up to 2 years
Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 2
Blood samples will be collected to assess change from baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count.
Measured: Baseline and up to 2 years
Change From Baseline in Hemoglobin Level-Part 2
Blood samples will be collected to assess change from baseline in hemoglobin level.
Measured: Baseline and up to 2 years
Change From Baseline in Hematocrit Level-Part 2
Blood samples will be collected to assess change from baseline in hematocrit level.
Measured: Baseline and up to 2 years
Change From Baseline in Erythrocytes Count-Part 2
Blood samples will be collected to assess change from Baseline in erythrocytes count.
Measured: Baseline and up to 2 years
Change From Baseline in Albumin and Total Protein Levels-Part 2
Blood samples will be collected to assess change from baseline in albumin and total protein levels.
Measured: Baseline and up to 2 years
Change From Baseline in Creatinine and Bilirubin Levels-Part 2
Blood samples will be collected to assess change from baseline in creatinine and bilirubin levels.
Measured: Baseline and up to 2 years
Change From Baseline in ALT, AST, ALP, LDH Levels-Part 2
Blood samples will be collected to assess change from baseline in ALT, AST ALP, LDH, amylase and lipase levels.
Measured: Baseline and up to 2 years
Change From Baseline in Amylase and Lipase Levels-Part 2
Blood samples were collected to assess change from baseline in amylase and lipase levels.
Measured: Baseline and up to 2 years
Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels -Part 2
Blood samples will be collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline.
Measured: Baseline and up to 2 years
Change From Baseline in Specific Gravity of Urine-Part 2
Urine samples will be collected to assess change from Baseline in specific gravity of urine.
Measured: Baseline and up to 2 years
Change From Baseline in pH of Urine-Part 2
Urine samples will be collected to assess change from baseline in pH of urine.
Measured: Baseline and up to 2 years
Number of Participants With Abnormal Urinalysis Parameters-Part 2
The dipstick test gives positive or negative results for protein, ketones, occult blood and glucose. Positive test results were considered as abnormal. Number of participants with positive test results were planned to be summarized.
Measured: Up to 2 years
Change From Baseline in TSH-Part 2
Blood samples will be collected to assess change from Baseline in TSH.
Measured: Baseline and up to 2 years
Change From Baseline in Free T3-Part 2
Blood samples will be collected to assess change from baseline in free T3.
Measured: Baseline and up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Nov 201816 Sep 2021

First posted3 Oct 2018
Study start26 Nov 2018
Primary completion25 Jun 2021
Study completion16 Sep 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: In Part 1, dose escalation will occur using a zone based approach. Part 2 will be randomized, parallel group study wherein the subjects will be randomized in a ratio of 2:1 to either recommended Phase 2 dose combination of GSK3359609 and tremelimumab or SOC (paclitaxel, docetaxel or cetuximab).
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03693612
Sponsor's protocol ID: 207871
Status last verified: Aug 2024
First submitted: 1 Oct 2018
Last updated: 28 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf

Publications

Hilton JF, Ott PA, Hansen AR, Li Z, Mathew M, Messina CH, Dave V, Ji X, Karpinich NO, Hirschfeld S, Ballas M, Zandberg DP. INDUCE-2: A Phase I/II, open-label, two-part study of feladilimab in combination with tremelimumab in patients with advanced solid tumors. Cancer Immunol Immunother. 2024 Feb 13;73(3):44. doi: 10.1007/s00262-023-03623-z.
PubMed 38349570

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
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Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
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Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II, Open-label, Two Part Study of GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors
ClinicalTrials.gov ID: NCT03693612
Acronym / sponsor ID: 207871
Conditions: Neoplasms
Keywords: advanced solid tumor, Head and Neck Squamous Cell Carcinoma, standard of care, GSK3359609, urothelial carcinoma of the upper and lower urinary tract, non-small cell lung cancer, cutaneous melanoma, Tremelimumab
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Collaborators: MedImmune LLC
Study start: 26 Nov 2018 (actual)
Primary completion: 25 Jun 2021 (actual)
Study completion: 16 Sep 2021 (actual)
First posted: 3 Oct 2018 (actual)
Results: Posted 22 Aug 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: In Part 1, dose escalation will occur using a zone based approach. Part 2 will be randomized, parallel group study wherein the subjects will be randomized in a ratio of 2:1 to either recommended Phase 2 dose combination of GSK3359609 and tremelimumab or SOC (paclitaxel, docetaxel or cetuximab).

Arm	Type	Receives
Part 1: feladilimab +tremelimumab	Experimental	Drug: feladilimab, Drug: TremelimumabIn Part 1, subjects with advanced selected solid tumors will be enrolled. Subjects will be administered escalating doses of feladilimab and tremelimumab in combination. feladilimab will be administered every 3 weeks and tremelimumab will be administered every 3 weeks for 6 doses and every 12 weeks thereafter.
Part 2: feladilimab +tremelimumab	Experimental	Drug: feladilimab, Drug: TremelimumabIn Part 2, subjects with R/R HNSCC who have disease progression after receiving at least one platinum-based chemotherapy and at least one anti-PD-1/PD-L1 will be enrolled. Subjects will be administered feladilimab in combination with tremelimumab at recommended Phase 2 dose as determined from Part 1.
Part 2: SOC	Active comparator	Drug: Docetaxel, Drug: Paclitaxel, Drug: CetuximabIn Part 2, subjects with R/R HNSCC who have disease progression after receiving at least one platinum-based chemotherapy and at least one anti-PD-1/PD-L1 will be enrolled. Subjects will be administered a single agent SOC therapy of either paclitaxel, docetaxel or cetuximab as per the investigators choice.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
Male or female, aged 18 years or older.
Body weight >=30 kilograms (kg).
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: a) Part 1: cutaneous melanoma; HNSCC (oral cavity, larynx, oropharynx, hypopharynx, nasal cavity/paranasal sinuses); non-small cell lung cancer (squamous and non-squamous); urothelial carcinoma of the upper and lower urinary tract; clear cell renal carcinoma; castrate resistant prostate adenocarcinoma. b) Part 2: HNSCC (oral cavity, larynx, pharynx, paranasal sinuses).
Part 1 only: 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, or where standard therapy is refused. May be anti-PD-1/anti-PD-L1 experienced or naïve.

Key exclusion criteria (21 listed)

Received prior treatment with the following therapies; calculation is based on date of last therapy to date of first dose of study intervention or SOC: a) Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4 [including tremelimumab] or Inducible T Cell Co-Stimulator (ICOS)-directed therapies at any time; b) >=4 lines of prior anticancer treatment: In subjects that relapse or progress within 1 year from the beginning of adjuvant or concurrent therapy, the adjuvant/concurrent therapy is considered first line therapy; c) Systemic anticancer therapy or investigational therapy within 30 days, or 5 half-lives, whichever is shorter; at least 14 days must have elapsed between the date of the last prior therapy to the date of first dose of study intervention or SOC.
Prior radiation therapy: permissible if at least one non-irradiated measurable lesion is available for assessment per RECIST v1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. At least 14 days must have elapsed between the date of the last dosage of radiation and the first dose of study intervention/SOC.
Invasive malignancy or history of invasive malignancy other than disease under study within the last two years, except: a) Any other invasive malignancy for which the subject was definitively treated, has been disease-free for <=2 years and in the opinion of the Investigator and Medical Monitor will not affect the evaluation of the effects of the study intervention or SOC on the currently targeted malignancy, may be included in this clinical study; Curatively treated non-melanoma skin cancer or successfully treated in-situ carcinoma.
Toxicity from previous anticancer treatment that includes: a) >=Grade 3 toxicity considered related to prior immunotherapy and that led to treatment discontinuation; b) Toxicity related to prior treatment that has not resolved to <=Grade 1 (except alopecia, vitiligo, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be <=Grade 2).
Central nervous system (CNS) metastases, with the following exception: Subjects with previously treated CNS metastases who are clinically stable and had no requirement for steroids during at least 14 days prior to first dose of study intervention or SOC.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
feladilimabfeladilimab is humanized anti-ICOS agonist immunoglobulin G (IgG) 4 monoclonal antibody (mAb), which will be administered as an intravenous (IV) infusion once every 3 weeks.	Drug	Part 1: feladilimab +tremelimumab, Part 2: feladilimab +tremelimumab
TremelimumabTremelimumab is humanized anti-CTLA-4 IgG2 mAb, which will be administered as an IV infusion once every 3 weeks for 6 doses, thereafter once every 12 weeks .	Drug	Part 1: feladilimab +tremelimumab, Part 2: feladilimab +tremelimumab
DocetaxelDocetaxel is a microtubule stabilizer which will be administered as an IV infusion once every 3 weeks at a dose of 75 milligrams per meter square (mg/m^2).	Drug	Part 2: SOC
PaclitaxelPaclitaxel is a microtubule stabilizer which will be administered as an IV infusion once weekly at a dose of 80 mg/m^2.	Drug	Part 2: SOC
CetuximabCetuximab is a recombinant, human/mouse chimeric anti-estimated glomerular filtration rate (EGFR) mAb. Cetuximab will be administered at a loading dose of 400 mg/m^2 followed by 250 mg/m^2 once weekly.	Drug	Part 2: SOC

Primary outcome

Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1
Time frame: Up to 28 days
A DLT is considered by the investigator to be clinically relevant, attributed event within first 28 days of intervention meeting the following criteria of toxicity, Hematologic: Febrile neutropenia, Grade 4 neutropenia of greater than (>) 7 days in duration or requiring Granulocyte- Colony stimulating factor (G-CSF), Grade 4 anemia and Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia; Non-hematologic: Grade 4 toxicity, Grade 3 pneumonitis, any greater than or equal to (≥) Grade 2 pneumonitis that does not resolve to less than or equal to (≤ ) Grade 1 within 3 days of the initiation of maximal supportive care, Grade 3 toxicity that does not resolve to Grade 1 or baseline within 3 days despite optimal supportive care and any Grade 2 ocular toxicity requiring systemic steroids, or any ≥ Grade 3 ocular toxicity.
Number of Participants With DLTs According to Severity-Part 1
Time frame: Up to 28 days
The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for ≤24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)-Part 1
Time frame: Up to 4 years
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An 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; is a congenital anomaly/birth defect and important medical events may jeopardize the subject or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before. AESIs are defined as events of potential immunologic etiology, including immune related AEs.
Number of Participant With AE/SAE/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1
Time frame: Up to 4 years
The number of participants with AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.
Number of Participants With AEs, SAEs, AESIs According to Severity - Part 1
Time frame: Up to 4 years
The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for ≤24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE.
Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1
Time frame: Up to 4 years
The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)-Part 1
Time frame: Baseline (Day 1) and Week 4
SBP and DBP were measured after 5 minutes of rest for the participant.
Change From Baseline in Temperature-Part 1
Time frame: Baseline (Day 1) and Week 4
Temperature was measured after 5 minutes of rest for the participant.
Change From Baseline in Pulse Rate-Part 1
Time frame: Baseline (Day 1) and Week 4
Pulse rate was measured after 5 minutes of rest for the participant.
Change From Baseline in Respiratory Rate-Part 1
Time frame: Baseline (Day 1) and Week 4
Respiratory rate was measured after 5 minutes of rest for the participant.
Change From Baseline in Oxygen Saturation-Part 1
Time frame: Baseline (Day 1) and Week 4
Oxygen saturation was measured using pulse oximeter after 5 minutes of rest for the participant.
Number of Participants With Electrocardiogram (ECG) Findings
Time frame: Baseline (Pre dose, Day 1) and up to 4 Years
Single 12-lead ECG was obtained using an automated ECG machine. ECG findings were categorized as: normal, abnormal - clinically significant (CS), or abnormal - not clinically significant (NCS), as determined by the investigator.
Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet counts.
Change From Baseline in Hemoglobin Level-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from baseline in hemoglobin level.
Change From Baseline in Hematocrit Level-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from baseline in hematocrit level.
Change From Baseline in Erythrocytes Count-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from baseline in Erythrocytes count.
Change From Baseline in Albumin and Total Protein Levels-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from Baseline in albumin and total protein levels.
Change From Baseline in Creatinine and Bilirubin Levels-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from baseline in creatinine and bilirubin levels.
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) Levels-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from baseline in ALT, AST ALP, LDH levels.
Change From Baseline in Amylase and Lipase Levels-Part 1
Time frame: Baseline (Day 1) and week 4
Blood samples were collected to assess change from baseline in amylase and lipase levels.
Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline.
Change From Baseline in Specific Gravity of Urine-Part 1
Time frame: Baseline (Day 1) and Week 4
Urine samples were collected to assess change from baseline in specific gravity of urine.
Change From Baseline in Potential of Hydrogen (pH) of Urine-Part 1
Time frame: Baseline (Day 1) and Week 4
Urine samples were collected to assess change from baseline in pH of urine.
Number of Participants With Abnormal Urinalysis Parameters-Part 1
Time frame: Week 4
The dipstick test gives positive or negative results for protein, ketones, occult blood and glucose in urine. Positive test results were considered as abnormal. Number of participants with positive test results have been summarized.
Change From Baseline in Thyroid Stimulating Hormone (TSH) or Thyrotropin-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from Baseline in TSH.
Change From Baseline in Free Triiodothyronine (T3)-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from Baseline in free T3.
Change From Baseline in Free Thyroxine (T4)-Part 1
Time frame: Baseline (Day 1) and Week 4
Blood samples were collected to assess change from baseline in free T4.
Overall Survival-Part 2
Time frame: Up to 4 years
For participants in Part 2, overall survival is defined as time from the date of randomization to the date of death due to any cause.

47 secondary outcomes

Overall Response Rate-Part 1
Time frame: Up to 4 years
Overall Response Rate-Part 2
Time frame: Up to 4 years
Disease Control Rate-Part 1
Time frame: Up to 4 years
Disease Control Rate-Part 2
Time frame: Up to 4 years
Progression Free Survival-Part 2
Time frame: Up to 4 years
Time to Response-Part 2
Time frame: Up to 4 years
Duration of Response-Part 2
Time frame: Up to 4 years
Maximum Observed Plasma Concentration (Cmax) of Feladilimab-Part 1
Time frame: Pre-dose, end of infusion and 4 hours post dose at Day 1
Cmax of Tremelimumab-Part 1
Time frame: Pre-dose, end of infusion and 4 hours post dose at Day 1
Cmax of Feladilimab-Part 2
Time frame: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, 19, 25, then every 12 weeks for 2 years; end of infusion at Weeks 1, 19 and 25; and 4 hours post-infusion at Week 1
Cmax of Tremelimumab-Part 2
Time frame: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, 19, 25, then every 12 weeks for 2 years; end of infusion at Weeks 1, 19 and 25; and 4 hours post-infusion at Week 1
Minimum Observed Plasma Concentration (Cmin) of Feladilimab-Part 1
Time frame: Pre-dose, end of infusion and 4 hours post dose at Day 1
Cmin of Tremelimumab-Part 1
Time frame: Pre-dose, end of infusion and 4 hours post dose at Day 1
Cmin of Feladilimab-Part 2
Time frame: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, then every 12 weeks for 2 years; end of infusion; and 4 hours post-infusion at Week 1
Cmin of Tremelimumab-Part 2
Time frame: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, then every 12 weeks for 2 years; end of infusion; and 4 hours post-infusion at Week 1
Area Under the Plasma Concentration-time Curve (AUC[0-t]) of Feladilimab-Part 1
Time frame: Pre-dose, end of infusion and 4 hours post dose at Day 1
AUC(0-t) of Tremelimumab-Part 1
Time frame: Pre-dose, end of infusion and 4 hours post dose at Day 1
AUC(0-t) of Feladilimab-Part 2
Time frame: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, 19, 25, then every 12 weeks for 2 years; end of infusion at Weeks 1, 19 and 25, and 4 hours post-infusion at Week 1
AUC(0-t) of Tremelimumab-Part 2
Time frame: Pre-dose at Weeks 1, 2, 4, 7, 10, 13, 16, then every 12 weeks for 2 years; end of infusion; and 4 hours post-infusion at Week 1
Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 1
Time frame: Pre-dose at Week 4, 7, 10 and 13
Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 1
Time frame: Pre-dose at Week 1, 4, 7, 10 and 13
Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 2
Time frame: Up to 2.5 years
Change From Baseline in Free T4-Part 2
Time frame: Baseline and up to 2 years
Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 2
Time frame: Up to 2.5 years
Number of Participants With AEs, SAEs and AESI-Part 2
Time frame: Up to 4 years
Number of Participants With AEs, SAEs, AESIs Based on Severity-Part 2
Time frame: Up to 4 years
Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 2
Time frame: Up to 4 years
Change From Baseline in SBP and DBP-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in Temperature-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in Pulse Rate-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in Respiratory Rate-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in Oxygen Saturation-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in ECG Measurement-Part 2
Time frame: Baseline (Pre-dose) up to 2 years
Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in Hemoglobin Level-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in Hematocrit Level-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in Erythrocytes Count-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in Albumin and Total Protein Levels-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in Creatinine and Bilirubin Levels-Part 2
Time frame: Baseline and up to 2 years
Change From Baseline in ALT, AST, ALP, LDH Levels-Part 2
Time frame: Baseline and up to 2 years

Results and safety

Results posted to the registry on 22 Aug 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg	1	1
Part 1: Feladilimab 24 mg + Tremelimumab 75 mg	1	0
Part 1: Feladilimab 8 mg + Tremelimumab 225 mg	5	4
Part 1: Feladilimab 80 mg + Tremelimumab 75 mg	3	3
Part 1: Feladilimab 24 mg + Tremelimumab 225 mg	16	10
Part 2: Feladilimab +Tremelimumab	0	0
Part 2: Standard of Care (SOC)	0	0

Primary outcome: Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1

Time frame: Up to 28 days. Count of participants. Unit: Participants

Measure	Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg n = 1	Part 1: Feladilimab 24 mg + Tremelimumab 75 mg n = 1	Part 1: Feladilimab 8 mg + Tremelimumab 225 mg n = 5	Part 1: Feladilimab 80 mg + Tremelimumab 75 mg n = 3	Part 1: Feladilimab 24 mg + Tremelimumab 225 mg n = 16
Value	0	0	0	0	1

Population analysed: All Treated Population includes all participants who received at least 1 dose of Tremelimumab or Feladilimab.

Primary outcome: Number of Participants With DLTs According to Severity-Part 1

Time frame: Up to 28 days. Count of participants. Unit: Participants

Measure	Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg n = 1	Part 1: Feladilimab 24 mg + Tremelimumab 75 mg n = 1	Part 1: Feladilimab 8 mg + Tremelimumab 225 mg n = 5	Part 1: Feladilimab 80 mg + Tremelimumab 75 mg n = 3	Part 1: Feladilimab 24 mg + Tremelimumab 225 mg n = 16
Grade 1	0	0	0	0	0
Grade 2	0	0	0	0	0
Grade 3	0	0	0	0	1
Grade 4	0	0	0	0	0
Grade 5	0	0	0	0	0

Population analysed: All Treated Population

Primary outcome: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)-Part 1

Time frame: Up to 4 years. Count of participants. Unit: Participants

Measure	Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg n = 1	Part 1: Feladilimab 24 mg + Tremelimumab 75 mg n = 1	Part 1: Feladilimab 8 mg + Tremelimumab 225 mg n = 5	Part 1: Feladilimab 80 mg + Tremelimumab 75 mg n = 3	Part 1: Feladilimab 24 mg + Tremelimumab 225 mg n = 16
AEs	1	1	5	3	16
SAEs	0	0	3	3	6
AESIs	0	0	2	0	7

Population analysed: All Treated Population

Primary outcome: Number of Participant With AE/SAE/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1

Time frame: Up to 4 years. Count of participants. Unit: Participants

Measure	Part 1: Feladilimab 8 mg + Tremelimumab 225 mg n = 5	Part 1: Feladilimab 24 mg + Tremelimumab 225 mg n = 16
Any Aes-Dose Modification	0	0
Any Aes-Dose Delay	3	4
Any Aes-Dose Withdrawal	1	3
Any SAEs-Dose Modification	0	0
Any SAEs-Dose Delay	1	1
Any SAEs-Dose Withdrawal	1	2
Any DLTs-Dose Modification	0	0
Any DLTs-Dose Delay	0	1

Population analysed: All Treated Population

47 secondary outcomes are reported in the full results.

Adverse events

Time frame: Non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected from Day 1 to upto 4 years. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Part 1: Feladilimab 24 mg + Tremelimumab 75 mg	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Part 1: Feladilimab 8 mg + Tremelimumab 225 mg	3 of 5 (60%)	5 of 5 (100%)	0 of 5
Part 1: Feladilimab 80 mg + Tremelimumab 75 mg	3 of 3 (100%)	3 of 3 (100%)	0 of 3
Part 1: Feladilimab 24 mg + Tremelimumab 225 mg	6 of 16 (37.5%)	16 of 16 (100%)	1 of 16
Part 2: Feladilimab + Tremelimumab	0 of 0	0 of 0	0
Part 2: Standard of Care (SOC)	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): The sponsor made the decision to not continue the study at the end of Part 1 based on the totality of available data due to lack of efficacy and not due to safety. Hence Part 2 was not initiated and participants were not enrolled in the same.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 38349570Hilton JF, Ott PA, Hansen AR, Li Z, Mathew M, Messina CH, Dave V, Ji X, Karpinich NO, Hirschfeld S, Ballas M, Zandberg DP. INDUCE-2: A Phase I/II, open-label, two-part study of feladilimab in combination with tremelimumab in patients with advanced solid tumors. Cancer Immunol Immunother. 2024 Feb 13;73(3):44. doi: 10.1007/s00262-023-03623-z.
Individual participant dataSharing planned: Yes. GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

8 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing feladilimab, Tremelimumab and Docetaxel in people with Neoplasms, run by GlaxoSmithKline at 8 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1 (time frame: Up to 28 days). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03693612, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2024.