A Study Comparing TAK-928 With Docetaxel in Adults With Non-Small Cell Lung Cancer

NCT07217301 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: CIBI363C3012026-525659-94-00jRCT2031260152
• Study Type: interventional
• Target: 600
• Locations: 3 countries
• Sites: 45

Brief Summary

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.

Conditions

IO-resistant sqNSCLC

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  From screening up to 26 months

Secondary Outcomes (20)

• Global and SRI Part: Objective Response Rate (ORR) as Assessed by Investigator per RECIST V1.1

  Up to 26 months

• Global Part: Progression-free survival (PFS), as Assessed by BICR and Investigator per RECIST V1.1

  Up to 26 months

• Global Part: Disease Control Rate (DCR) as Assessed by BICR and Investigator per RECIST V1.1

  Up to 26 months

• Global Part: Duration of Response (DOR) as Assessed by BICR and Investigator per RECIST V1.1

  Up to 26 months

• Global Part: Time to Response (TTR) as Assessed by BICR and Investigator per RECIST V1.1

  Up to 26 months

Study Arms (2)

TAK-928

EXPERIMENTAL

TAK-928 is a first-in-class bispecific monoclonal antibody (mAb) comprised of an interleukin-2 (IL-2) mutein fused with a recombinant anti-programmed cell death protein 1 (anti-PD-1) mAb. TAK-928 was precisely designed and constructed to afford targeted binding of tumor-specific CD8+ T cells (TSTs) that co-express PD-1 and CD25 (IL2Ra) receptors. The mechanism of action of TAK-928 is blocking the PD-(L)1 and activating the IL-2 pathways simultaneously to reverse T cell exhaustion and promote activation of T cells and natural killer (NK) cells, and consequently eliminate tumor cells.

Drug: TAK-928

Control

ACTIVE COMPARATOR

Docetaxel or comparable generic brand

Drug: Control Arm

Interventions

Control Arm DRUG

Comparator product will be administered by IV infusion.

Control

TAK-928 DRUG

TAK-928 will be administered by IV infusion.

TAK-928

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• Have locally unresectable advanced or metastatic histologically or cytologically confirmed squamous 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.
• 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.
• \- 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.
• 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.
• \- 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.
• Provide formalin-fixed tumor tissue specimen. 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (45)

St. Bernards Healthcare

Jonesboro, Arkansas, 72401, United States

RECRUITING

Memorial Care

Fountain Valley, California, 92708, United States

RECRUITING

Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720, United States

RECRUITING

Translation Research in Oncology- US, INC (TRIO-US)

Torrance, California, 90505, United States

RECRUITING

D & H Cancer Research Center

Margate, Florida, 33063, United States

RECRUITING

BRCR Global

Tamarac, Florida, 33322, United States

RECRUITING

The University of Texas M.D Anderson Cancer Center (MDACC)

Houston, Texas, 77030, United States

RECRUITING

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230022, China

RECRUITING

Anhui Provincial Cancer Hospital

Hefei, Anhui, 230088, China

NOT YET RECRUITING

Anhui Provincial Hospital

Hefei, Anhui, 231501, China

RECRUITING

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

NOT YET RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, 400030, China

RECRUITING

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400042, China

RECRUITING

The Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350004, China

RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

RECRUITING

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510080, China

NOT YET RECRUITING

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Guangzhou, Guangdong, 510095, China

RECRUITING

The Fourth Hospital of Hebei University

Shijiazhuang, Hebei, 050011, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

NOT YET RECRUITING

The First Affiliated Hospital of Xinxiang Medical University

Xinxiang, Henan, 453100, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

RECRUITING

Henan Provincial People's Hospital

Zhengzhou, Henan, 450003, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

NOT YET RECRUITING

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410205, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

WITHDRAWN

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221006, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

Liaoning Cancer Hospital

Shenyang, Liaoning, 110042, China

RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

RECRUITING

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

NOT YET RECRUITING

The First Affiliated Hospital of Xi'An Jiaotong University

Xi'an, Shannxi, 710061, China

RECRUITING

Sichuan Cancer Hospital

Chengdu, Sichuan, 610213, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 611135, China

NOT YET RECRUITING

The Affiliated Hospital of Southwest Medical University

Luzhou, Sichuan, 646000, China

RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300000, China

NOT YET RECRUITING

Yunnan Cancer Hospital

Kunming, Yunnan, 650118, China

NOT YET RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

NOT YET RECRUITING

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

NOT YET RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325015, China

NOT YET RECRUITING

National Cancer Center

Tokyo, 104-0045, Japan

RECRUITING

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Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Central Study Contacts

Takeda Contact

CONTACT

877-825-3327; medinfoUS@takeda.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2025
• First Posted: October 15, 2025
• Study Start: November 26, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

CN (37); JP (1); US (7)