Neoplasms
Conditions
Brief summary
This study is a sub-study of the master protocol 205801 (NCT03739710). This sub study has assessed the clinical activity of novel regimen (Feladilimab plus Docetaxel) with SOC (Docetaxel) in participants with NSCLC.
Interventions
DRUGDocetaxel
Docetaxel was administered as IV infusion.
DRUGFeladilimab
Feladilimab was administered as IV infusion.
Sponsors
iTeos Belgium SA
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants capable of giving signed informed consent/assent. * Male or female, aged 18 years or older at the time consent is obtained. Participants in Korea must be age 19 years or older at the time consent is obtained. * Participants with histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous) and a) Documented disease progression based on radiographic imaging, during or after a maximum of 2 lines of systemic treatment for locally/regionally advanced recurrent, Stage IIIb/Stage IIIc/Stage IV or metastatic disease. Two components of treatment must have been received in the same line or as separate lines of therapy: i) No more than or less than 1 line of platinum-containing chemotherapy regimen, and ii) No more than or less than 1 line of Programmed cell death ligand 1 (PD\[L\]1) monoclonal antibody (mAb) containing regimen. b) Participants with known BRAF molecular alterations must have had disease progression after receiving the locally available SoC treatment for the molecular alteration. c) Participants who received prior anti-PD(L)1 therapy must fulfill the following requirements: i) Have achieved a CR, PR or SD and subsequently had disease progression (per RECIST 1.1 criteria) either on or after completing PD(L)1 therapy ii) Have not progressed or recurred within the first 12 weeks of PD(L)1 therapy, either clinically or per RECIST 1.1 criteria * Measurable disease, presenting with at least 1 measurable lesion per RECIST 1.1. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1. * A tumor tissue sample obtained at any time from the initial diagnosis of NSCLC to time of study entry is mandatory. Although a fresh tumor tissue sample obtained during screening is preferred, archival tumor specimen is acceptable. * Adequate organ function as defined in the protocol. * A male participant must agree to use a highly effective contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions apply: i) Not a woman of childbearing potential (WOCBP) or ii) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment. * Life expectancy of at least 12 weeks.
Exclusion criteria
* Participants who received prior treatment with the following therapies (calculation is based on date of last therapy to date of first dose of study treatment): 1. Docetaxel at any time. 2. Any of the investigational agents being tested in the current study. 3. Systemic approved or investigational 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. 4. Prior radiation therapy: permissible if at least one non-irradiated measurable lesion is available for assessment per RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least 2 weeks before start of study drug for radiation of any intended use is required. * Received greater than (\>)2 prior lines of therapy for NSCLC, including participants with BRAF molecular alternations. * Invasive malignancy or history of invasive malignancy other than disease under study within the last 2 years, except * Any other invasive malignancy for which the participant was definitively treated, has been disease-free for at least 2 years and in the opinion of the principal investigator and GlaxoSmithKline 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. * Curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma. * Carcinomatous meningitis (regardless of clinical status) and uncontrolled or symptomatic Central nervous system (CNS) metastases. * Major surgery less than or equal to (\<=) 28 days of first dose of study treatment. * 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 (for example, adrenal insufficiency) are not considered systemic treatments. * Receiving systemic steroids (\>10 milligrams \[mg\]) oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to first dose of study treatment. * Prior allogeneic/autologous bone marrow or solid organ transplantation. * Receipt of any live vaccine within 30 days prior to first dose of study treatment. * Toxicity from previous anticancer treatment that includes: 1. Greater than or equal to (\>=) Grade 3 toxicity considered related to prior immunotherapy and that led to treatment discontinuation. 2. Toxicity related to prior treatment that has not resolved to \<= Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be \<= Grade 2). * History (current and past) of idiopathic pulmonary fibrosis, pneumonitis (for past- pneumonitis exclusion only if steroids were required for treatment), interstitial lung disease, or organizing pneumonia. * Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions. * Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess. * History or evidence of cardiac abnormalities within the 6 months prior to enrollment which include 1. Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third degree atrioventricular block. 2. Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting or bypass grafting. 3. Symptomatic pericarditis. * Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypo-albuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. * Active infection requiring systemic therapy \<=7 days prior to first dose of study treatment. * Participants with known human immunodeficiency virus infection. * Participants with history of severe hypersensitivity to mAb or hypersensitivity to any of the study treatment(s) or their excipients. * Participants requiring ongoing therapy with a medication that is a strong inhibitor or inducer of the cytochrome P 3A4 (CYP3A4) enzymes. * Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other condition that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures in the opinion of the investigator. * Pregnant or lactating female participants. * Participant who is currently participating in or has participated in a study of an investigational device within 4 weeks prior to the first dose of study treatment. * Participants with presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention. * Participants with positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention. * Participants with positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. * Receipt of 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, and recombinant erythropoietin) within 14 days before the first dose of study intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 2 years | Overall survival was calculated as time from randomization to death. Confidence Intervals estimated using the Brookmeyer Crowley method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Up to 2 years | CR, PR, SD and PD will be evaluated as per RECIST version 1.1 criteria. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. |
| Kaplan-Meier Estimates of Progression-Free Survival (PFS) | Up to 2 years | PFS is defined as time from the date of randomization to the date of disease progression as per RECIST v1.1. or death whichever occurs earlier. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. Confidence Intervals estimated using the Brookmeyer Crowley method. |
| Objective Response Rate | Up to 2 years | ORR was calculated as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. |
| Kaplan-Meier Estimates of Duration of Response (DOR) in Participants With Objective Response | Up to 2 years | DOR is defined as the time for first documented evidence of CR or PR until disease progression or death, per RECIST 1.1 criteria. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Confidence Intervals estimated using the Brookmeyer Crowley method. |
| Disease Control Rate (DCR) | Up to 2 years | DCR is defined as the percentage of participants with a confirmed CR + PR at any time, plus SD =\>12 weeks as per RECIST v1.1. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. |
| Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | Up to 2 years | Modified RECIST 1.1 for immune-based therapeutics (iRECIST) is based on RECIST v 1.1 but adapted to account for the unique tumor response seen with immunotherapeutic drugs. iRECIST was used to assess tumor response and progression and make treatment decisions. iCR: disappearance of all target lesions; iPR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). iCPD: either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; iSD: stable disease in the absence of CR or PD and iUPD: unconfirmed progressive disease when PD is unconfirmed and NE: not evaluable. |
| Kaplan-Meier Estimates of iRECIST Progression-free Survival (iPFS) | Up to 2 years | iPFS is defined as time from the date of randomization to the date of disease progression or death, whichever occurs earlier, per iRECIST criteria. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. Confidence Intervals estimated using the Brookmeyer Crowley method. |
| iRECIST Objective Response Rate (iORR) | Up to 2 years | iORR is defined as the percentage of participants with a confirmed iCR or iPR at any time per iRECIST criteria. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. |
| Kaplan-Meier Estimates of iRECIST Duration of Response (iDOR) in Participants With Objective Response | Up to 2 years | iDOR is defined as the time from first documented evidence of CR or PR until disease progression or death, per iRECIST criteria. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Confidence Intervals estimated using the Brookmeyer Crowley method. |
| Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | Up to 2 years | An AE was defined as 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 was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. AESI are considered to be Infusion Related Reactions (IRRs) and those of potential immunologic etiology. |
| Kaplan-Meier Estimates of Overall Survival at 12 and 18 Months | Month 12 and 18 | Overall survival was defined as the time between date of randomization and death due to any cause. Kaplan-Meier estimates of the percentage of participants who died at each time point was calculated. Confidence Intervals estimated using the Brookmeyer Crowley method. |
| Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Up to 2 years | Blood samples were collected for assessment of the hematology parameters. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE. Number of participants with Hematology results by maximum grade increase (Increase to Grade 3 or Increase to Grade 4) are presented. |
| Number of Participants With Maximum Grade Increase in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Parameters at Worst Case Post-Baseline | Up to 2 years | Blood Pressure was measured after 5 minutes of rest and was taken in the same position throughout the study. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE. Number of participants with vital signs results by maximum grade increase (Increase to Grade 2 or Increase to Grade 3) are presented. |
| Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline | Up to 2 years | Body temperature was measured after 5 minutes of rest. Results are presented in the following categories: Decrease to \<=35 Degrees Celsius, Change to Normal or No Change and Increase to \>=38 Degrees Celsius. |
| Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline | Up to 2 years | Pulse Rate was measured after 5 minutes of rest. Results are presented in the following categories: Decrease to \<50 beats per minute, Change to Normal or No Change and Increase to \>120 beats per minute. |
| Minimum Observed Concentration (CmIn) of Feladilimab | Week 1 | Blood samples were collected for assessment of the pharmacokinetic parameters. |
| Maximum Observed Concentration (Cmax) of Feladilimab | Week 1, Week 13 and Week 25 | Blood samples were collected for assessment of the pharmacokinetic parameters. |
| Maximum Observed Concentration (Cmax) of Docetaxel | Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19 and Week 22 | Blood samples were collected for assessment of the pharmacokinetic parameters. |
| Number of Participants With Positive Anti-drug Antibodies (ADA) Against Docetaxel | Up to 2 years | — |
| Number of Participants With Positive ADA Against Feladilimab | Week 1, 4, 7, 10, 13, 16, 19, 22, 25, 37, 49, 61 and 73 | — |
| Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline | Up to 2 years | Blood samples were collected for assessment of the clinical chemistry parameters. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE. Number of participants with clinical chemistry results by maximum grade increase (Increase to Grade 3 or Increase to Grade 4) are presented. |
Countries
Canada, France, Germany, Italy, Netherlands, Poland, Romania, Russia, South Korea, Spain, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel 75 mg/m^2 Participants with NSCLC were administered with Docetaxel 75 milligram per meter square (mg/m\^2) monotherapy as intravenous (IV) infusion once every 3 weeks (Q3W). | 35 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 Participants with NSCLC were administered with Feladilimab 80 mg IV infusion Q3W in combination with Docetaxel 75 mg/m\^2 IV infusion Q3W. | 70 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 25 | 62 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Site Closed | 6 | 6 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Total | Docetaxel 75 mg/m^2 |
|---|---|---|---|
| Age, Continuous | 64.4 years STANDARD_DEVIATION 9.11 | 63.8 years STANDARD_DEVIATION 9.57 | 62.6 years STANDARD_DEVIATION 10.48 |
| Age, Customized 18-64 | 31 Participants | 53 Participants | 22 Participants |
| Age, Customized 65-74 | 28 Participants | 35 Participants | 7 Participants |
| Age, Customized 75-84 | 11 Participants | 16 Participants | 5 Participants |
| Age, Customized >=85 | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants | 102 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Canada | 0 participants | 3 participants | 3 participants |
| Region of Enrollment France | 9 participants | 15 participants | 6 participants |
| Region of Enrollment Germany | 7 participants | 10 participants | 3 participants |
| Region of Enrollment Italy | 7 participants | 11 participants | 4 participants |
| Region of Enrollment Netherlands | 3 participants | 3 participants | 0 participants |
| Region of Enrollment Poland | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Romania | 9 participants | 11 participants | 2 participants |
| Region of Enrollment Russia | 5 participants | 8 participants | 3 participants |
| Region of Enrollment South Korea | 5 participants | 9 participants | 4 participants |
| Region of Enrollment Spain | 13 participants | 17 participants | 4 participants |
| Region of Enrollment Sweden | 2 participants | 2 participants | 0 participants |
| Region of Enrollment United States | 7 participants | 12 participants | 5 participants |
| Sex: Female, Male Female | 17 Participants | 25 Participants | 8 Participants |
| Sex: Female, Male Male | 53 Participants | 80 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 25 / 34 | 62 / 70 |
| other Total, other adverse events | 31 / 34 | 66 / 70 |
| serious Total, serious adverse events | 16 / 34 | 34 / 70 |
Outcome results
Primary
Overall Survival
Overall survival was calculated as time from randomization to death. Confidence Intervals estimated using the Brookmeyer Crowley method.
Time frame: Up to 2 years
Population: Intent To Treat population (ITT) included all participants who were randomized to treatment regardless of whether the participants actually received study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel 75 mg/m^2 | Overall Survival | 8.2 Months |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Overall Survival | 7.8 Months |
Secondary
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed CR + PR at any time, plus SD =\>12 weeks as per RECIST v1.1. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Time frame: Up to 2 years
Population: Intent-to-Treat Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel 75 mg/m^2 | Disease Control Rate (DCR) | 40 Percentage of Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Disease Control Rate (DCR) | 50 Percentage of Participants |
Secondary
iRECIST Objective Response Rate (iORR)
iORR is defined as the percentage of participants with a confirmed iCR or iPR at any time per iRECIST criteria. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
Time frame: Up to 2 years
Population: Intent-to-Treat population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel 75 mg/m^2 | iRECIST Objective Response Rate (iORR) | 11 Percentage of Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | iRECIST Objective Response Rate (iORR) | 19 Percentage of Participants |
Secondary
Kaplan-Meier Estimates of Duration of Response (DOR) in Participants With Objective Response
DOR is defined as the time for first documented evidence of CR or PR until disease progression or death, per RECIST 1.1 criteria. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Confidence Intervals estimated using the Brookmeyer Crowley method.
Time frame: Up to 2 years
Population: Intent To Treat Population. Only participants who achieved Objective Response were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of Duration of Response (DOR) in Participants With Objective Response | 4.8 Months |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of Duration of Response (DOR) in Participants With Objective Response | 4.3 Months |
Secondary
Kaplan-Meier Estimates of iRECIST Duration of Response (iDOR) in Participants With Objective Response
iDOR is defined as the time from first documented evidence of CR or PR until disease progression or death, per iRECIST criteria. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Confidence Intervals estimated using the Brookmeyer Crowley method.
Time frame: Up to 2 years
Population: Intent-To-Treat Population. Only the participants with Objective Response were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of iRECIST Duration of Response (iDOR) in Participants With Objective Response | 4.8 Months |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of iRECIST Duration of Response (iDOR) in Participants With Objective Response | 4.3 Months |
Secondary
Kaplan-Meier Estimates of iRECIST Progression-free Survival (iPFS)
iPFS is defined as time from the date of randomization to the date of disease progression or death, whichever occurs earlier, per iRECIST criteria. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. Confidence Intervals estimated using the Brookmeyer Crowley method.
Time frame: Up to 2 years
Population: Intent-to-Treat population. Only those participants with data available at specified data points have been analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of iRECIST Progression-free Survival (iPFS) | 3.3 Months |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of iRECIST Progression-free Survival (iPFS) | 3.4 Months |
Secondary
Kaplan-Meier Estimates of Overall Survival at 12 and 18 Months
Overall survival was defined as the time between date of randomization and death due to any cause. Kaplan-Meier estimates of the percentage of participants who died at each time point was calculated. Confidence Intervals estimated using the Brookmeyer Crowley method.
Time frame: Month 12 and 18
Population: Intent-To-Treat Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of Overall Survival at 12 and 18 Months | Month 12 | 44 Percentage of Participants |
| Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of Overall Survival at 12 and 18 Months | Month 18 | 28 Percentage of Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of Overall Survival at 12 and 18 Months | Month 12 | 28 Percentage of Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of Overall Survival at 12 and 18 Months | Month 18 | 18 Percentage of Participants |
Secondary
Kaplan-Meier Estimates of Progression-Free Survival (PFS)
PFS is defined as time from the date of randomization to the date of disease progression as per RECIST v1.1. or death whichever occurs earlier. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. Confidence Intervals estimated using the Brookmeyer Crowley method.
Time frame: Up to 2 years
Population: Intent to Treat Population. Only those participants with data available at specified data points have been analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of Progression-Free Survival (PFS) | 3.3 Months |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Kaplan-Meier Estimates of Progression-Free Survival (PFS) | 3.4 Months |
Secondary
Maximum Observed Concentration (Cmax) of Docetaxel
Blood samples were collected for assessment of the pharmacokinetic parameters.
Time frame: Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19 and Week 22
Population: Pharmacokinetic Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 1 | 1500.9 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 133.5 |
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 4 | 1587.1 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 128.6 |
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 7 | 846.8 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 166.4 |
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 10 | 1262.9 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 155.4 |
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 13 | 1354.2 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 212.1 |
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 16 | 1095.3 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 114.3 |
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 19 | 759.0 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 74 |
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 22 | 535.5 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 10.9 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 22 | 2430.7 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 73.3 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 1 | 1429.9 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 138.7 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 13 | 1363.4 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 137.8 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 4 | 1399.7 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 99.3 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 19 | 1765.7 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 95.1 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 7 | 1036.9 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 171.2 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 16 | 1381.9 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 114 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Docetaxel | Week 10 | 1248.4 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 118.3 |
Secondary
Maximum Observed Concentration (Cmax) of Feladilimab
Blood samples were collected for assessment of the pharmacokinetic parameters.
Time frame: Week 1, Week 13 and Week 25
Population: Pharmacokinetic population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Feladilimab | Week 1 | 24923.7 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 26.7 |
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Feladilimab | Week 13 | 28715.9 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 45.4 |
| Docetaxel 75 mg/m^2 | Maximum Observed Concentration (Cmax) of Feladilimab | Week 25 | 32688.4 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 27.4 |
Secondary
Minimum Observed Concentration (CmIn) of Feladilimab
Blood samples were collected for assessment of the pharmacokinetic parameters.
Time frame: Week 1
Population: Pharmacokinetic (PK) population will consist of all participants from the ITT Population from whom a blood sample was obtained and analyzed for PK concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Minimum Observed Concentration (CmIn) of Feladilimab | 6104.6 nanogram per millimeter (ng/mL) | Geometric Coefficient of Variation 91.3 |
Secondary
Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals
An AE was defined as 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 was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. AESI are considered to be Infusion Related Reactions (IRRs) and those of potential immunologic etiology.
Time frame: Up to 2 years
Population: Safety Population included all the randomized participants who received at least one dose of Standard of Care (SoC), or experimental regimen based on actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AEs leading to dose interruption/delay | 11 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AESI | 1 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AEs | 34 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | SAEs | 16 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AEs leading to dose reduction | 7 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AEs leading to permanent discontinuation of study treatment | 12 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AEs | 70 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AEs leading to dose reduction | 13 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AEs leading to dose interruption/delay | 24 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AEs leading to permanent discontinuation of study treatment | 16 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | AESI | 4 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals | SAEs | 34 Participants |
Secondary
Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable
CR, PR, SD and PD will be evaluated as per RECIST version 1.1 criteria. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm.
Time frame: Up to 2 years
Population: Intent-To-Treat Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Partial Response | 4 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Progressive Disease | 14 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Stable Disease | 10 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Not Evaluable | 7 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Complete Response | 0 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Not Evaluable | 12 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Complete Response | 0 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Partial Response | 13 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Stable Disease | 22 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable | Progressive Disease | 23 Participants |
Secondary
Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable
Modified RECIST 1.1 for immune-based therapeutics (iRECIST) is based on RECIST v 1.1 but adapted to account for the unique tumor response seen with immunotherapeutic drugs. iRECIST was used to assess tumor response and progression and make treatment decisions. iCR: disappearance of all target lesions; iPR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). iCPD: either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; iSD: stable disease in the absence of CR or PD and iUPD: unconfirmed progressive disease when PD is unconfirmed and NE: not evaluable.
Time frame: Up to 2 years
Population: Intent-To-Treat Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iCR | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iPR | 4 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iUPD | 11 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iCPD | 3 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iSD | 10 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | Not Evaluable | 7 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iSD | 22 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iCR | 0 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iCPD | 8 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iPR | 13 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | Not Evaluable | 12 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable | iUPD | 15 Participants |
Secondary
Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline
Blood samples were collected for assessment of the clinical chemistry parameters. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE. Number of participants with clinical chemistry results by maximum grade increase (Increase to Grade 3 or Increase to Grade 4) are presented.
Time frame: Up to 2 years
Population: Safety Population. Only those participants with data available at specified data points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline | Hypercalcemia | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline | Creatinine increased | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline | Blood bilirubin increased | 0 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline | Hypercalcemia | 2 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline | Creatinine increased | 1 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline | Blood bilirubin increased | 1 Participants |
Secondary
Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline
Blood samples were collected for assessment of the hematology parameters. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE. Number of participants with Hematology results by maximum grade increase (Increase to Grade 3 or Increase to Grade 4) are presented.
Time frame: Up to 2 years
Population: Safety Population. Only those participants with data available at specified data points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Anemia | 2 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Leukocytosis | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | White blood cell decreased | 5 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Lymphocyte count decreased | 4 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Neutrophil count decreased | 4 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Platelet count decreased | 0 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Neutrophil count decreased | 13 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Anemia | 5 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Lymphocyte count decreased | 12 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Leukocytosis | 1 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | Platelet count decreased | 3 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline | White blood cell decreased | 11 Participants |
Secondary
Number of Participants With Maximum Grade Increase in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Parameters at Worst Case Post-Baseline
Blood Pressure was measured after 5 minutes of rest and was taken in the same position throughout the study. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE. Number of participants with vital signs results by maximum grade increase (Increase to Grade 2 or Increase to Grade 3) are presented.
Time frame: Up to 2 years
Population: Safety Population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Parameters at Worst Case Post-Baseline | Systolic Blood Pressure | 16 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Parameters at Worst Case Post-Baseline | Diastolic Blood Pressure | 12 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Parameters at Worst Case Post-Baseline | Systolic Blood Pressure | 28 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Maximum Grade Increase in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Parameters at Worst Case Post-Baseline | Diastolic Blood Pressure | 26 Participants |
Secondary
Number of Participants With Positive ADA Against Feladilimab
Time frame: Week 1, 4, 7, 10, 13, 16, 19, 22, 25, 37, 49, 61 and 73
Population: Safety population. Only those participants with data available at specified time points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 49 | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 1 | 1 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 4 | 8 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 7 | 4 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 10 | 2 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 13 | 2 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 16 | 1 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 19 | 2 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 22 | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 25 | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 37 | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 61 | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Positive ADA Against Feladilimab | Week 73 | 0 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADA) Against Docetaxel
Time frame: Up to 2 years
Population: Data was not collected.
Secondary
Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline
Pulse Rate was measured after 5 minutes of rest. Results are presented in the following categories: Decrease to \<50 beats per minute, Change to Normal or No Change and Increase to \>120 beats per minute.
Time frame: Up to 2 years
Population: Safety Population. Only those participants with data available at specified data points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline | Decrease to <50 beats per minute | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline | Change to Normal or No Change | 32 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline | Increase to >120 beats per minute | 2 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline | Decrease to <50 beats per minute | 0 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline | Change to Normal or No Change | 55 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline | Increase to >120 beats per minute | 8 Participants |
Secondary
Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline
Body temperature was measured after 5 minutes of rest. Results are presented in the following categories: Decrease to \<=35 Degrees Celsius, Change to Normal or No Change and Increase to \>=38 Degrees Celsius.
Time frame: Up to 2 years
Population: Safety Population. Only those participants with data available at specified data points have been analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline | Decrease to <=35 Degrees Celsius | 0 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline | Change to Normal or No Change | 33 Participants |
| Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline | Increase to >=38 Degrees Celsius | 1 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline | Decrease to <=35 Degrees Celsius | 6 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline | Change to Normal or No Change | 52 Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline | Increase to >=38 Degrees Celsius | 5 Participants |
Secondary
Objective Response Rate
ORR was calculated as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be \<10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
Time frame: Up to 2 years
Population: Intent-To-Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel 75 mg/m^2 | Objective Response Rate | 11 Percentage of Participants |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | Objective Response Rate | 19 Percentage of Participants |