A Randomized, Open Label, Multicenter, Phase 3 Trial Evaluating the Efficacy and Safety of TAK-928 Versus Docetaxel in Participants With Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Disease Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy (MarsLight-11)
A Study Comparing TAK-928 With Docetaxel in Adults With Non-Small Cell Lung Cancer (MarsLight-11)
Murakami Naoko
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Contact for Clinical Trial Information
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Recruiting
Nov. 26, 2025
Nov. 26, 2025
600
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
1. Must be able to understand and willing to sign the written informed consent form (ICF), be able to comply with the visit schedule and related procedures specified in the protocol.
2. Male or female participants must be at least 18 years old or the legal age of majority in their country, whichever is greater. For Japan-specific safety run-in (SRI) part of the trial, participants must be Japanese residing in Japan.
3. Have locally unresectable advanced or metastatic histologically or cytologically confirmed squamous Non-Small Cell Lung Cancer (NSCLC). Mixed small cell carcinoma, or other pathological components are excluded.
Note: For Japan-specific SRI only: Participants' histology is not restricted to squamous NSCLC and may include all metastatic or unresectable solid tumor participants.
4. Have had disease progression on or after prior treatment with anti-PD-1/PD-L1 therapy and platinum-based doublet chemotherapy (for example, carboplatin and paclitaxel), given either concurrently or sequentially. Eligible participants include those that have:
- Received platinum-based chemotherapy in combination with anti-PD-1/PD-L1 therapy as the only prior line of therapy.
OR
- Received platinum-based chemotherapy and anti-PD-1/PD-L1 therapy sequentially (in either order) as the only 2 prior lines of therapy.
Note: For Japan-specific SRI only: Participants must be refractory OR intolerant to standard of care (SOC) treatment.
5. Participants that have received prior anti-PD-1/PD-L1 therapy with curative intent for locally advanced disease are eligible if they meet either of the following criteria:
- Received prior platinum-based chemotherapy with or without radiotherapy with maintenance anti-PD-1/PD-L1 therapy for Stage III disease and relapsed/progressed within 6 months from the last dose of platinum-based chemotherapy.
OR
- Received prior peri-operative platinum-based chemotherapy with maintenance anti-PD-1/PD-L1 therapy for resectable Stage II/III and have relapsed within 6 months from the last dose of platinum-based chemotherapy.
Note: For Japan-specific SRI only: This criterion is not applicable for Japanese participants enrolled in the SRI part of the trial.
6. Provide formalin-fixed tumor tissue specimen for PD-L1 expression level testing and exploratory analysis of other biomarkers. Fresh biopsies are preferred but archival specimens collected within 2 years before signing the informed consent form are acceptable (blocks or 10-15 unstained slides sectioned 4-5 microns in thickness, if tissue slides, they must be sectioned from blocks less than or equal to (<=) 2 months from date of consent). Formalin-fixed paraffin-embedded (FFPE) blocks are preferred for submission; slides should be sent only if there is a local regulation preventing submission of the FFPE block. Ideally, the archival specimen should be collected subsequent to the most recent systemic therapy.
Note: For Japan-specific SRI only: Collection of tumor tissue specimen is not required for Japanese participants enrolled in the SRI part of the trial.
7. Have at least 1 measurable lesion (target lesion) by computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) V1.1. Lesions that have previously received radiotherapy or intratumoral injection can only be used as measurable lesions if they show progression after treatment (either pathologically confirmed or with observation of radiographic progression more than 3 months after treatment) as per RECIST V1.1.
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
9. Expected survival time greater than or equal to (>=) 3 months.
10. Women of childbearing potential (WOCBP) must take a urine or serum pregnancy test, highly sensitive tests are required where available based on region, and must test negative for trial inclusion. WOCBP must agree to use at least 1 form of highly effective contraception and 1 barrier method of contraception during the entire course of treatment and for 6 months after the last dose of trial treatment. Fertile men must agree to use a condom, preferably combined with at least 1 form of acceptable contraception for any WOCBP partner(s) during the entire course of treatment and for 6 months after the last dose of trial intervention.
11. Lactating women must agree to strictly abstain from breastfeeding during the entire Treatment Period and for 6 months after the treatment.
1. Women who are pregnant or breastfeeding, or intending to become pregnant before, during, or within 6 months after the last dose of any trial intervention. WOCBP not using and/or not willing to use at least 1 form of highly effective method of contraception and 1 barrier method of contraception or fertile men with WOCBP partner(s) not using and/or not willing to use at least 1 form of acceptable contraception.
Note: If in the investigator's judgment, the participant may be pregnant based on the physician's medical interview or other information, the participant will be excluded from the trial irrespective of a negative pregnancy test.
2. Known actionable genomic alteration, including any of the following driver gene mutations:
- Epidermal growth factor receptor (EGFR): including exon 19 deletion, exon 21 L858R, exon 20 T790M, exon 20 S768I, exon 21 L861Q, exon 18 G719X, and exon 20 insertion mutations.
- Kirsten rat sarcoma virus (KRAS) G12C mutation.
- Anaplastic lymphoma kinase (ALK) rearrangement.
- ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) rearrangement.
- B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation.
- Neurotrophic tyrosine receptor kinase (NTRK) 1/2/3 fusion.
- MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping mutation.
- RET proto-oncogene (RET) rearrangement.
- V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2, also known as HER2) mutation.
Note: (a) It is not mandatory to have undergone driver gene testing. (b) For Japan-specific SRI only: This criterion is not applicable for Japanese participants enrolled in the SRI part of the trial.
3. Participants with enlarging or symptomatic brain metastases are excluded from the trial. Participants who are neurologically, clinically and radiologically stable >=4 weeks after definitive treatment for brain metastases and participants with small, asymptomatic, incidental, untreated brain metastases that remain radiographically stable >= 4 weeks after initial identification may participate in this trial as long as they meet all of the following criteria:
- No metastases to meninges, midbrain, pons, medulla oblongata (leptomeningeal metastases), or cerebellar metastases.
- No compression of the aqueduct of Sylvius, no compression of the third or fourth ventricle.
- No participant with epidural spinal cord compression or spinal cord metastases.
- Participants must be off steroids for at least 7 days for CNS disease. Systemic steroids of <=10 milligrams per day (mg/day) of prednisone or equivalent are acceptable if needed for other indications.
- CNS-related symptoms must be stable >= 14 days prior to randomization.
- Brain metastases should not be included as RECIST V1.1 target lesions
4. Presence of any of the following hematologic abnormalities at baseline*:
- Hemoglobin < 9 grams per deciliter (g/dL).
- Absolute neutrophil count (ANC) < 1,500 per cubic millimeters (mm^3).
- Platelet (PLT) count <100 x 10^3/mm^3.
* Baseline is defined as the last available observation prior to the first dose of investigational product. Note: Participants must not receive supportive treatments such as blood products (including RBC suspension, apheresis platelets, cryoprecipitation, and so on.), within 7 days of confirming eligibility. Erythropoietin or colony-stimulating factors must not be administered within 28 days of confirming eligibility.
5. Presence of any of the following serum chemistry abnormalities at baseline:
- Total bilirubin greater than (>) 1.5 x upper limit of normal (ULN) except for participants with Gilbert's syndrome with serum bilirubin <= 3 x ULN or if concurrent conjugated bilirubin <= ULN.
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN; for liver metastasis, AST or ALT > 5 x ULN.
- Creatinine clearance (CrCl) < 30 milliters per minute (mL/min); the Cockcroft-Gault formula is used to calculate CrCl (using ideal body weight for obese participants and actual body weight for non-obese participants).
- Albumin < 30 grams per liter (g/L).
Note: Investigator should follow local practice guidelines and/or the docetaxel label approved in the country of intervention administration for assessing eligibility of participants for the trial.
6. Presence of any of the following coagulation parameter abnormalities at baseline:
- International normalized ratio (INR) > 1.5 x ULN (> 3 x ULN if on stable dose anticoagulation).
- Partial thromboplastin time (PTT; or activated partial thromboplastin time [aPTT]) > 1.5 x ULN (> 3 x ULN if on stable-dose anticoagulation).
7. History of deep venous thrombosis, pulmonary embolism, or any other serious thromboembolic events within 30 days prior to enrollment (implantable port or catheter-related thrombosis, or superficial venous thrombosis are not considered "serious" thromboembolisms). Participants with a history of serious thromboembolic event must be asymptomatic and on stable anticoagulation therapy (if such therapy is deemed necessary by the treating physician).
8. Active uncontrolled bleeding, known bleeding diathesis, or significant concern for risk of acute life-threatening bleeding (for example, radiographic evidence that tumor invades large blood vessels or has unclear boundaries with a major vessel [including aorta, left pulmonary artery, right pulmonary artery, pulmonary vein, superior vena cava, inferior vena cava, and so on], or the investigator judges that the tumor is very likely to invade major vessels with the potential to cause fatal bleeding during the duration of the trial).
9. Presence of clinically significant cardiovascular or cerebrovascular diseases, including:
- Symptomatic, clinically unstable arrhythmia or arrhythmia requiring clinical intervention.
- Severe conduction disorders (such as third-degree atrioventricular block and bundle branch block).
- QT interval corrected for heart rate (QTc interval, calculated using Fridericia's formula) >= 480 milliseconds (msec).
- Uncontrolled hypertension (systolic blood pressure >= 160 millimeters of mercury (mmHg) or diastolic blood pressure >= 100 mmHg) despite standard treatment.
- History of myocarditis.
- Left ventricular ejection fraction < 50 percent (%).
- Congestive heart failure requiring treatment.
- Class II-IV cardiac insufficiency according to the New York Heart Association functional classification.
- History of acute coronary syndrome (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to the first dose of investigational product.
- Cerebrovascular accident or transient ischemic attack within 6 months before the first dose of the investigational product.
- History of seizures unless controlled on stable dose of antiseizure medications.
10. Cardiac enzymes >= levels consistent with acute myocardial infarction as defined by laboratory-specific criteria. Participants with isolated Grade 1 elevated cardiac enzymes require cardiology clearance and consultation with the sponsor's medical monitor to confirm absence of ongoing myocardial/ischemic disease.
18age old over
No limit
Both
Immuno-oncology Resistant Squamous Non-Small Cell Lung Cancer
TAK-928 Arm:
Priming dose: 0.1 mg/kg on Day 1 of Cycle 1 (C1D1) Intended dose: 3 mg/kg every 3 weeks (Q3W) starting Day 8 of Cycle 1 (C1D8) Cycle duration: 28 days for Cycle 1, then 21 days from Cycle 2 onward Dose adjustments: Up to 2 reductions (1.5 mg/kg or 1 mg/kg Q3W) allowed for adverse events (AEs) Re-priming protocol: Required if delays in dosing exceed defined thresholds (e.g., >10 days post-priming or >=5 weeks since last dose)
Control Arm:
75 mg/m^2 every 3 weeks (Q3W), starting from C1D1 21-day cycle duration Dose Reduction: as per label
1. 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
Time Frame: Up to 26 months
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.
2. Global Part: Overall Survival (OS)
Time Frame: Up to 26 months
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.
3. SRI Part: Percentage of Participants with Dose-limiting Toxicities (DLTs)
Time Frame: Up to 28 days after first dose (Day 1)
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.
4. 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
Time Frame: From screening up to 26 months
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.
1. Global and SRI Part: Objective Response Rate (ORR) as Assessed by Investigator per RECIST V1.1
Time Frame: Up to 26 months
The proportion of participants with a best overall response of complete response (CR) or partial response (PR), per RECIST v1.1
2. Global Part: Progression-free survival (PFS), as Assessed by BICR and Investigator per RECIST V1.1
Time Frame: Up to 26 months
Investigator and BICR assessed PFS per RECIST v1.1.
3. Global Part: Disease Control Rate (DCR) as Assessed by BICR and Investigator per RECIST V1.1
Time Frame: Up to 26 months
The proportion of participants who achieve CR, PR, or stable disease (SD) per RECIST v1.1.
4. Global Part: Duration of Response (DOR) as Assessed by BICR and Investigator per RECIST V1.1
Time Frame: Up to 26 months
Time of first documented CR or PR to the time of disease progression or death.
5. Global Part: Time to Response (TTR) as Assessed by BICR and Investigator per RECIST V1.1
Time Frame: Up to 26 months
Time from randomization to the first occurrence of a response (CR or PR) per RECIST v1.1.
6. SRI Part: DCR as Assessed by Investigator per RECIST V1.1
Time Frame: Up to 26 months
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).
7. SRI Part: DOR as Assessed by Investigator per RECIST V1.1
Time Frame: Up to 26 months
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.
8. SRI Part: TTR as Assessed by Investigator per RECIST V1.1
Time Frame: Up to 26 months
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.
9. Global Part: Percentage of Participants With TEAEs, irAEs, SAEs, AESIs and TEAEs Leading to Discontinuation and Deaths
Time Frame: From screening up to 26 months
Percentage of participants with: TEAEs /Treatment-Related Adverse Events (TRAEs) any grade / >= grade 3; Treatment-Emergent Serious Adverse Events (TESAEs) /Treatment-Related Serious Adverse Events (TRSAEs); AESI (defined in protocol); irAEs any grade/ >= grade 3; TEAEs /TRAEs leading to interruption/discontinuation/death; infusion related reactions any grade/ >= grade 3.
10. Global and SRI Part: Pharmacokinetic parameters including Terminal Half-Life of TAK-928
Time Frame: Day 1 pre-dose and at multiple time points post-dose (up to 25 months)
The terminal elimination half life will be calculated from the terminal phase of the plasma concentration-time curve.
11. Global and SRI Part: Pharmacokinetic parameters including Clearance (CL) of TAK-928
Time Frame: Day 1 pre-dose and at multiple time points post-dose (up to 25 months)
Clearance will be calculated using dose/AUC.
12. Global and SRI Part: Pharmacokinetic parameters including Volume of Distribution (Vd) of TAK-928
Time Frame: Day 1 pre-dose and at multiple time points post-dose (up to 25 months)
Volume of distribution will be estimated based on non-compartmental analysis.
13. Global and SRI Part: Number of Participants Who Develop Anti-Drug Antibodies (ADA) and/or Neutralizing Antibody (Nab) to TAK-928
Time Frame: Up to 25 months
Positive rates of anti-TAK-928 antibody (ADA) and/or neutralizing antibody (NAb) in participants receiving TAK-928 are planned to evaluate.
14. Global Part: Time to Deterioration (TTD) in GHS/QoL and Dyspnea as Measured by the EORTC QLQ-C30
Time Frame: Up to 25 months
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.
15. 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)
Time Frame: Up to 25 months
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).
16. Global Part: Change From Baseline in Functioning Scale Scores as Measured by the EORTC QLQ-C30
Time Frame: Up to 25 months
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.
17. Global Part: Change From Baseline in Symptom Scale Scores as Measured by the EORTC QLQ-C30
Time Frame: Up to 25 months
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.
18. Global Part: Change From Baseline in Single Item Symptom Questions as Measured by the EORTC QLQ-C30
Time Frame: Up to 25 months
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.
19. Global Part: Change From Baseline in Health Utility Scores as Measured by EuroQol Five-dimensional Five-level Questionnaire (EQ-5D-5L)
Time Frame: Up to 25 months
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.
Takeda Pharmaceutical Company Limited
Innovent Biologics (Suzhou) Co. Ltd.
National Cancer Center Japan Institutional Review Board
5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan, Tokyo
+81-3-3542-2511
Approval
Yes
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
