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

Recruiting now · Phase 3

Conditions studied: IO-resistant sqNSCLC

In brief

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.

Key facts

Study ID: NCT07217301
Run by: Takeda
People needed: 600
Starts: 2025-11-26
Expected to finish: 2029-12-01
Last updated by the study team: 2026-08-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
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.
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.
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.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
Expected survival time greater than or equal to (>=) 3 months.
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.
Lactating women must agree to strictly abstain from breastfeeding during the entire Treatment Period and for 6 months after the treatment.

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.
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
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.
Presence of any of the following serum chemistry abnormalities at baseline:
Total bilirubin greater than (>) 1.5×upper limit of normal (ULN) except for participants with Gilbert's syndrome with serum bilirubin <=3×ULN or if concurrent conjugated bilirubin <=ULN.

Where it is running

The First Affiliated Hospital of Xi'An Jiaotong University — Xi'an, Shannxi, China (enrolling)
Apex Research — Fair Oaks, California, United States (enrolling)
Memorial Care — Fountain Valley, California, United States (enrolling)
Cancer and Blood Specialty Clinic — Los Alamitos, California, United States (enrolling)
Translation Research in Oncology- US, INC (TRIO-US) — Torrance, California, United States (enrolling)
D & H Cancer Research Center — Margate, Florida, United States (enrolling)
BRCR Global — Tamarac, Florida, United States (enrolling)
The University of Texas M.D Anderson Cancer Center (MDACC) — Houston, Texas, United States (enrolling)
The First Affiliated Hospital of Anhui Medical University — Hefei, Anhui, China (enrolling)
The Third Xiangya Hospital of Central South University — Changsha, Hunan, China (enrolling)
Nanjing Drum Tower Hospital — Nanjing, Jiangsu, China (enrolling)
Jiangsu Province Hospital — Nanjing, Jiangsu, China (enrolling)
The Affiliated Hospital of Xuzhou Medical University — Xuzhou, Jiangsu, China (enrolling)
The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (enrolling)
Liaoning Cancer Hospital — Shenyang, Liaoning, China (enrolling)
Shandong Cancer Hospital — Jinan, Shandong, China (enrolling)
Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (enrolling)
St. Bernards Healthcare — Jonesboro, Arkansas, United States (enrolling)
Sichuan Cancer Hospital — Chengdu, Sichuan, China (enrolling)
The Affiliated Hospital of Southwest Medical University — Luzhou, Sichuan, China (enrolling)
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (enrolling)
National Cancer Center — Tokyo, Japan (enrolling)
Anhui Provincial Hospital — Hefei, Anhui, China (enrolling)
Beijing Cancer Hospital — Beijing, Beijing Municipality, China (enrolling)
Chongqing University Cancer Hospital — Chongqing, Chongqing Municipality, China (enrolling)

Full record on ClinicalTrials.gov

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