Lung cancer is one of the most common forms of cancer. One common type is non-small cell lung cancer (NSCLC). NSCLC happens when abnormal cells in the lungs grow too fast. This can stop the lungs from working normally. This study focuses on NSCLC in later stages (advanced). This means that the cancer has spread to other parts of the body (metastatic) or cannot be removed with surgery (unresectable). People with unresectable, advanced or metastatic NSCLC often get treatment with immunotherapy and/or platinum-based chemotherapy (such as cisplatin or carboplatin). Immunotherapy helps the body's germ-fighting (immune) system fight cancer. Chemotherapy kills cancer cells or slows their growth. Over time, these treatments may stop working and the cancer can get worse. Researchers are looking for ways to make immunotherapy work better. One approach is to help the immune system recognize cancer more easily by activating certain cells, called T cells, to attack and kill the tumor cells. TAK-928 is designed to attach to T cells in the tumor and make them more active and abundant. This may help the body fight the cancer and destroy tumor cells. The main aim of this study is to learn how well TAK-928 works and compares with the usual treatment (also called standard of care), docetaxel, in adults with unresectable, advanced or metastatic NSCLC. Another aim is to learn how safe TAK-928 is in adults with NSCLC. The participants can be treated for up to 2 years (24 months) depending on how a participant responds, side effects, or other reasons. Researchers will check a participant's condition until the treatment is ended. During the study, participants will visit the study clinic several times.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
600
TAK-928 will be administered by IV infusion.
Comparator product will be administered by IV infusion.
St. Bernards Healthcare
Jonesboro, Arkansas, United States
RECRUITINGApex Research
Fair Oaks, California, United States
RECRUITINGMemorial Care
Fountain Valley, California, United States
RECRUITINGCancer and Blood Specialty Clinic
Los Alamitos, California, United States
Global Part: Confirmed Objective Response Rate (cORR) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (V)1.1
cORR is defined as the proportion of participants with confirmed objective response rate (complete response \[CR\] or partial response \[PR\]) per RECIST V1.1 CR is defined as complete disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non- target) must have reduction in short axis to less than (\<) 10 mm. PR is defined as at least a 30 percent decrease in the sum of the diameters of target lesions, taking as reference the Baseline sum diameters.
Time frame: Up to 26 months
Global Part: Overall Survival (OS)
To compare the overall survival (OS) of TAK-928 (treatment group) versus docetaxel (control group) in participants with unresectable locally advanced or metastatic squamous NSCLC with disease progression on or after platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy.
Time frame: Up to 26 months
SRI Part: Percentage of Participants with Dose-limiting Toxicities (DLTs)
DLT will be defined as any of the adverse events (AEs) specified in the protocol that occur within the DLT observation period, is not attributable to disease or other extraneous factors and potentially related to the intervention following the first dose. Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Time frame: Up to 28 days after first dose (Day 1)
SRI Part: Percentage of Participants With Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAEs), Immune-Related Adverse Events (irAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation and Deaths
AE: Any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial intervention, whether or not there is a causal relationship with any trial intervention, including, but not limited to, following: Exacerbation of pre-existing medical conditions/diseases (including worsening of symptoms, signs, laboratory abnormalities) temporally associated with the use of trial intervention; any newly developed adverse medical conditions (including symptoms, signs and newly diagnosed diseases) and clinically significant abnormal laboratory values or results. TEAE: Any AE that starts after the first administration of study drug. SAE: Any untoward medical occurrence that meets at least one of the following criteria: Results in death; is life threatening; requires inpatient hospitalization or prolongation of hospitalization. irAEs may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously.
Time frame: From screening up to 26 months
Global and SRI Part: Objective Response Rate (ORR) as Assessed by Investigator per RECIST V1.1
The proportion of participants with a best overall response of complete response (CR) or partial response (PR), per RECIST v1.1.
Time frame: Up to 26 months
Global Part: Progression-free survival (PFS), as Assessed by BICR and Investigator per RECIST V1.1
Investigator and BICR assessed PFS per RECIST v1.1.
Time frame: Up to 26 months
Global Part: Disease Control Rate (DCR) as Assessed by BICR and Investigator per RECIST V1.1
The proportion of participants who achieve CR, PR, or stable disease (SD) per RECIST v1.1.
Time frame: Up to 26 months
Global Part: Duration of Response (DOR) as Assessed by BICR and Investigator per RECIST V1.1
Time of first documented CR or PR to the time of disease progression or death.
Time frame: Up to 26 months
Global Part: Time to Response (TTR) as Assessed by BICR and Investigator per RECIST V1.1
Time from randomization to the first occurrence of a response (CR or PR) per RECIST v1.1.
Time frame: Up to 26 months
SRI Part: DCR as Assessed by Investigator per RECIST V1.1
DCR is defined as the proportion of participants who have achieved CR, PR, or stable disease (SD) after the initiation of trial intervention (per RECIST V1.1).
Time frame: Up to 26 months
SRI Part: DOR as Assessed by Investigator per RECIST V1.1
DOR is defined as the time interval from first CR or PR until the first date of disease progression per RECIST V1.1 or death due to any cause, whichever occurs first, for participants with confirmed objective responses.
Time frame: Up to 26 months
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Translation Research in Oncology- US, INC (TRIO-US)
Torrance, California, United States
RECRUITINGD & H Cancer Research Center
Margate, Florida, United States
RECRUITINGBRCR Global
Tamarac, Florida, United States
RECRUITINGThe University of Texas M.D Anderson Cancer Center (MDACC)
Houston, Texas, United States
RECRUITINGThe First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, China
RECRUITINGAnhui Provincial Cancer Hospital
Hefei, Anhui, China
NOT_YET_RECRUITING...and 36 more locations
SRI Part: TTR as Assessed by Investigator per RECIST V1.1
TTR is defined as the time interval from the date of randomization to the first CR or PR for participants with confirmed objective responses per RECIST V1.1.
Time frame: Up to 26 months
Global Part: Percentage of Participants With TEAEs, irAEs, SAEs, AESIs and TEAEs Leading to Discontinuation and Deaths
Percentage of participants with: TEAEs/TRAEs any grade / \>= grade 3; TESAEs/TRSAEs; AESI (defined in protocol); irAEs any grade/ \>= grade 3; TEAEs/TRAEs leading to interruption/discontinuation/death; infusion related reactions any grade/ \>= grade 3.
Time frame: From screening up to 26 months
Global and SRI Part: Pharmacokinetic parameters including Terminal Half-Life (t½) of TAK-928
The terminal elimination half-life will be calculated from the terminal phase of the plasma concentration-time curve.
Time frame: Day 1 pre-dose and at multiple time points post-dose (up to 25 months)
Global and SRI Part: Pharmacokinetic parameters including Clearance (CL) of TAK-928
Clearance will be calculated using dose/AUC.
Time frame: Day 1 pre-dose and at multiple time points post-dose (up to 25 months)
Global and SRI Part: Pharmacokinetic parameters including Volume of Distribution (Vd) of TAK-928
Volume of distribution will be estimated based on non-compartmental analysis.
Time frame: Day 1 pre-dose and at multiple time points post-dose (up to 25 months)
Global and SRI Part: Number of Participants Who Develop Anti-Drug Antibodies (ADA) and/or Neutralizing Antibody (Nab) to TAK-928
Positive rates of anti-TAK-928 antibody (ADA) and/or neutralizing antibody (NAb) in participants receiving TAK-928 are planned to evaluate.
Time frame: Up to 25 months
Global Part: Time to Deterioration (TTD) in in GHS/QoL and Dyspnea as Measured by the EORTC QLQ-C30
TTD is defined as the time from baseline to the occurrence of first clinical meaningful deterioration compared to baseline score of EORTC QLQ-C30. Participants without deterioration will be censored at the date of last assessment prior to the data cutoff date.
Time frame: Up to 25 months
Global Part: Change from Baseline in Global Health Status (GHS)/ Quality of Life (QoL) Score (Item 29 & 30) and Dyspnea (Item 8) Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
GHS/QoL will be assessed using the EORTC QLQ-C30. Scores range from 0 to 100. For the Global Health Status/QoL scale, a higher score indicates a better outcome (i.e., better QoL). The change from baseline to each time point will be analyzed. Change in QoL was assessed using participant responses to questions regarding Global Health Status (Q29: GHS; "How would you rate your overall health during the past week?") and QoL (Q30: QoL; "How would you rate your overall quality of life during the past week?") and were scored on a 7-point scale (1= Very poor to 7=Excellent).
Time frame: Up to 25 months
Global Part: Change From Baseline in Functioning Scale Scores as Measured by the EORTC QLQ-C30
EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), GHS and QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. Scale scores can be obtained for the multi-item scales. The functioning items are scored on a 4-point scale (1=Not at All to 4=Very Much). Scores are linearly transformed on a scale of 0 to 100, with a high score indicating better functioning.
Time frame: Up to 25 months
Global Part: Change From Baseline in Symptom Scale Scores as Measured by the EORTC QLQ-C30
EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), GHS and QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. Scale scores can be obtained for the multi-item scales. The symptom items are scored on a 4-point scale (1=Not at All to 4=Very Much). Scores are linearly transformed on a scale of 0 to 100, with a high score indicating worst symptoms.
Time frame: Up to 25 months
Global Part: Change From Baseline in Single Item Symptom Questions as Measured by the EORTC QLQ-C30
EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), global health status (GHS) and quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. Scale scores can be obtained for the multi-item scales. The single items are scored on a 4-point scale (1=Not at All to 4=Very Much). Scores are linearly transformed on a scale of 0 to 100, with a high score indicating worst symptoms.
Time frame: Up to 25 months
Global Part: Change From Baseline in Health Utility Scores as Measured by EuroQol Five-dimensional Five-level Questionnaire (EQ-5D-5L)
The EQ-5D-5L was a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score for use in health economic analysis. The EQ-5D-5L has two components: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/ depression, as well as a Visual Analogue Scale (VAS) that measures health state. Each item was rated from 1 (no problems) to 5 (extreme problems). Higher score indicates best health status.
Time frame: Up to 25 months
Global Part: Change From Baseline in Symptoms of Lung Cancer as Assessed With the EORTC QLQ- Lung Cancer (LC) 13 (QLQ-LC13)
The EORTC QLQ-LC13 contains 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Subscales are scored on a range of 0 to 100. Higher symptom score indicates a greater degree of symptom severity.
Time frame: Up to 25 months